Nick Adler began his Martial Arts training in 1956 receiving rank in both Judo and Jujitsu as well as Okinawan Isshinryu Karate. He currently holds Dan rank under both Grandmaster Don Nagle and Grandmaster Angi Uezu and is the number one student to both of them. He is the director of the Nick Adler's Centurions, a 14 school association with over 2,000 members in six states.
Shihan Adler is an internationally licensed instructor and graduate of the Long Island University Instructor Certification program. He holds Menkyo Kai from Master Uezu which is the highest license an instructor can award. He holds Kyoshi in Kobudo from the USKA and Renshi in Kobudo from Grandmaster Seikichi Odo.
Sensei Adler has been featured in "Who's who in Isshinryu", "Who's Who in Karate", "Who's Who in American Martial Arts" and "Masters, Founders and Leaders of American Martial Arts". He is listed as "Sensei of the Year" for 1974 and 1980 in Ron Van Clief's books.
In 1981, Sensei Adler received S. Henry Cho's All American Award for karate, the same year he became "Man of the Year" in the Ying Yee Hall of Fame. He was awarded "Male Instructor of the Year" in 1984 by the International Isshin-Ryu Hall of Fame, and inducted in 1988. Karate International awarded Mr. Adler the "East Coast Pioneer's Award", in 1989.
In 1994 he received special recognition from the AOKA and in 1996 he was inducted into the World Head of Family Sokeship Council Hall of Fame receiving the "Golden Lifetime Achievement" award with 40 years in the martial arts and was the recipient of several awards at Don Nagle's Hall of Fame in September 1997.


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Hyptiotes cavatus är en spindelart som först beskrevs av Nicholas Marcellus Hentz 1847.  Hyptiotes cavatus ingår i släktet Hyptiotes och familjen krusnätsspindlar. Inga underarter finns listade i Catalogue of Life.

Källor

Krusnätsspindlar
cavatus

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Apache Junction Computer Repair Service has been providing the best mobile computer repair in Apache Junction, AZ and the greater Phoenix Metro Area since 1999. The term "mobile computer repair" means we come to you, to your home or business, to resolve all your computer problems.
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Q: how to index mysql table on two similar indexes contents? I have a mysql database table with the following columns : a1, a2, a3, a4, b1, b2, b3 b4.
I need to do heavy search on the records therefore I would like to index the table properly.
Sometimes, I need to search (a1,a2,a3,b1,b2), sometimes I need to search (a1,a2,a3,b1,b3,b4).
Shall I do two indexes like
INDEX  search1  (a1,a2,a3,b1,b2),
INDEX  search2  (a1,a2,a3,b1,b3,b4),

Or, is there any good way for me do the INDEX just once and it can work well in both cases?

A: The answer depends a bit on what your query really looks like.  If the first four columns (a1, a2, a3, b1) are highly selective, then either is fine.  The index should be used for both queries.  Of course, it will be more optimized for the query that matches all the columns.
There isn't a way, though, to have "one" index that handles both sets of columns.
If these sets of columns are the only columns used in the query, then the indexes "cover" their respective queries.  This means that all the information for the query is in the index and doesn't need the original data pages.  If you want such covering indexes, but only want one, then you could add all the columns to one of the indexes:
a1, a2, a3, b1, b3, b4, b2

The next consideration is how often the table is being updated.  Maintaining two indexes requires twice the index time as maintaining one index.  Is this an issue for the queries?  If so, you might want to lean towards only one index.

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Andrei Platonov was a Soviet Russian writer, playwright, and poet, whose works anticipate existentialism.
Although Platonov was a Communist, most of his works were banned in his own lifetime for their skeptical attitude toward collectivization and other Stalinist policies, as well as for its experimental, avant-garde form.
"Happiness will come from materialism, not from meaning."


As experienced broadcast journalists, Media-Vu's business communication specialists are perectly equipped to sniff-out a good story.
Media-Vu offers a business set of professional communication services. The beating heart of each service is the story Media-Vu's professionals are able to find and then use to pump-out a clear and constant messaging.
You can tell that just from the experience you have of those who are winging it, hoping for the best and others who have thought about it and are delivering a much clearer message. Often, usually, mainly when they are winging it or haven't prepared it where they are speaking off the cusp, that is where the stories develop because they say things they don't really want to say and from a Journalistic point of view, that's fantastic, that's the story. News is something somebody doesn't want you to hear and that is what it's all about.


Outdoor Retailer's Winter and Summer Market in Salt Lake City has been a home away from home for BCM. We always enjoy our time visiting with friends, volunteers, and sponsors; and sharing our successes from the past season while promoting our upcoming work in the field. This past Winter OR was particularly special because we were recognized in front of our peers as an Inspiration Award Winner in the Nonprofit category.
It was an incredible honor to be nominated alongside 1% For the Planet and Veteran's Expeditions, but to win in front of over 500 attendees was mind blowing. Presented by Adidas Outdoor, the Inspiration Awards were created 6 years ago to celebrate those "that inspire and encourage others in their communities to enjoy, participate in and support outdoor activities and the outdoor industry." Other categories that were recognized include: Individual (Andy Janicki), Manufacturer (LifeStraw), Retailer, (Alpenglow Sports), and Youth (Jackie Timmins).
We want to offer our thanks and appreciation to the judging panel that included Greg Thomsen, John Stewart of the Boy Scouts of America, Kristin Hostetter, representing AIM Media, Lisa Hennessy from Dreamjobbing, Rue Mapp of OIA / Outdoor Afro and Dieter Tremp from ISPO. Moreover, thank you to the event's key sponsors, adidas Outdoor and Boy Scouts of America, along with media partners OR Daily, SNEWS and DreamJobbing.


Sarge's Deli is one of the few old-world Jewish style delicatessens left in New York. From the authentic Tiffany's stained glass lamps to the celebrity photos that line the southern wall, this place has the charm you come to expect from institutions of the like. The website was designed to bring the warm & cozy feelings you get when dining in Sarge's to the website utilizing fantastic photography and a clever narrative.
The highlight feature is a unique image gallery that detail the specialty sandwich items served at Sarge's. Think you can tackle The Monster? You may think again after comparing it do some of the other offerings. Additionally, the responsive design optimizes the site for desktop, tablet, and mobile devices.


Hi everyone, and thank you for visiting.
Recently I was asked to speak about nutrition and wellness to a group of women. Sugar was the most popular topic.
The truth is that for women, 24gm of sugar is the maximum amount daily. Men should keep their intake at 32 gm. Sugar is sugar. There are no excuses. Bread, yogurt, pastries (doughnuts, cookies, candy..) juices, pasta, milk, corn and carbohydrates and unfortunately alcohol. Two slices of whole wheat bread has 10 teaspoons of sugar, compared to a Snicker Bar that has 8.5.. the Snicker Bar would be the choice of many.. just saying.
I will try to simplify this topic of SUGAR.
The best option is to make "healthier choices". Dannon and some other name brands of yogurt with fruit has a whopping 27 grams of sugar. Choose Fage yogurt, it has 16 grams. It also has separate compartments so you can add just the right amount of sweetness that you like. It taste just as good, or better. Fruits, which are suppose to be healthy, and they are, were the first topic of discussion at my nutrition engagement. Fruits and vegetables are very healthy, but certain fruits have lots of sugar. Be aware of the food that you are eating daily.
Here is an example: The cantaloupe, 1 medium melon contains 43g of sugar. Grapes, Figs, Mangos, Prunes Raisin's and Apricots are also very high in sugar content. Making the "healthier choice" here would be choosing Berries, Blackberries, Blueberries, Strawberries, Apples, Olives and Avocado's, (yes they are considered a fruit). This could be the only reason that if you are working out like a crazy person and still not loosing weight it could be your daily intake of SUGAR.
Empower yourself, read labels, and become knowledgeable. Be accountable for the life that you have been given.
The Bottom Line : The danger of SUGARS is simply the amount of glucose, simple sugars, that it puts into the blood. High blood glucose levels lead to diabetes type 2, Heart disease and mostly Cancer. Cancer feeds off of SUGAR.
This was in an article from YourNewsWire.com, May 22,2017. For anyone watching their sugar intake.
This is so true.. thank you for sharing Pat..
Your Teeth are an Important Guideline to your health!


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Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus
Roland W. Herzog, J. Nathan Hagstrom, Szu-Hoo Kung, Shing Jen Tai, James M. Wilson, Krishna J. Fisher, and Katherine A. High
PNAS May 27, 1997 94 (11) 5804-5809; https://doi.org/10.1073/pnas.94.11.5804
Roland W. Herzog
J. Nathan Hagstrom
Szu-Hoo Kung
Shing Jen Tai
James M. Wilson
Krishna J. Fisher
Katherine A. High
We sought to determine whether intramuscular injection of a recombinant adeno-associated virus (rAAV) vector expressing human factor IX (hF.IX) could direct expression of therapeutic levels of the transgene in experimental animals. High titer (1012–1013 vector genomes/ml) rAAV expressing hF.IX was prepared, purified, and injected into hindlimb muscles of C57BL/6 mice and Rag 1 mice. In the immunocompetent C57BL/6 mice, immunofluorescence staining of muscle harvested 3 months after injection demonstrated the presence of hF.IX protein, and PCR analysis of muscle DNA was positive for AAV DNA, but no hF.IX was detected in mouse plasma. Further studies showed that these mice had developed circulating antibodies to hF.IX. In follow-up experiments in Rag 1 mice, which carry a mutation in the recombinase activating gene-1 and thus lack functional B and T cells, similar results were seen on DNA analysis of muscle, but these mice also demonstrated therapeutic levels (200–350 ng/ml) of F.IX in the plasma. The time course of F.IX expression demonstrates that levels gradually increase over a period of several weeks before reaching a plateau that is stable 6 months after injection. In other experiments we demonstrate colocalization of hF.IX and collagen IV in intersitial spaces between muscle fibers. Collagen IV has recently been identified as a F.IX-binding protein; this finding explains the unusual pattern of immunofluorescent staining for F.IX shown in these experiments. Thus rAAV can be used to direct stable expression of therapeutic levels of F.IX after intramuscular injection and is a feasible strategy for treatment of patients with hemophilia B.
Recent reports demonstrate significant progress in the area of gene therapy by in vivo expression of a transgene after direct injection of the vector into skeletal muscle. Adenoviral vectors were used in this manner to express high levels of canine blood coagulation factor IX (F.IX) in immunodeficient mice or in conjunction with immunosuppressive agents to avoid an otherwise strong inflammatory and cytotoxic T lymphocyte response to adenoviral-transduced muscle fibers (1). Other studies suggest that intramuscular injection of replication defective adenovirus can provide long-term expression if the transgene encodes a self-protein so that a strong host immune response is avoided (2, 3). Plasmid DNA injected into mouse muscle directed expression of erythropoietin (4), but has not been shown to be efficient enough for the expression of a gene product such as F.IX, which must be present at much higher levels in the circulation to achieve a therapeutic effect.
Adeno-associated virus (AAV) represents an alternative vehicle for gene delivery into muscle. Recombinant AAV (rAAV) does not contain sequences encoding viral proteins and has the potential to integrate into the chromosomal DNA of the host cell (5, 6). Production and purification procedures are now available that allow the generation of rAAV without significant contamination with wild-type AAV or the helper adenovirus (6–8). While the efficiency of in vivo transduction with rAAV in the absence of helper virus is low for hepatocytes and airway epithelial cells (7), certain postmitotic cells, such as neurons (9) and skeletal muscle fibers (10, 11), can be effectively transduced. Stable expression of lacZ for up to 1½ years has been reported (11). In contrast to adenoviral vectors, intramuscular injection with rAAV in immunocompetent animals does not result in cytotoxic T lymphocyte response against transduced muscle fibers, nor are circulating antibodies against the intracellular lacZ gene product present (10). Based on Southern blot and PCR analysis of genomic DNA from skeletal muscle injected with rAAV, other investigators concluded that rAAV genomes persisted as tandem repeats integrated into chromosomal DNA (10, 11).
There has been a single report of expression of a secreted protein, erythropoietin, after intramuscular injection with rAAV (12), but the levels of protein expression reported (vide infra) were 1–2 orders of magnitude below that needed for a coagulation protein such as F.IX. In this study, we report stable expression (at least 6 months) of therapeutic levels of human F.IX (hF.IX) after intramuscular injection of adult mice with an AAV-F.IX vector. Expression was demonstrated for muscle tissue of immunocompetent animals and reached levels of 200–350 ng/ml in plasma of immunodeficient mice. Therefore, intramuscular injection with rAAV represents a promising approach to provide stable therapeutic amounts of hF.IX in the systemic circulation of hemophilia B patients.
Production and Purification of rAAV.
rAAV was generated by cotransfection of a F.IX cis plasmid (pAAV-F.IX) and the trans-acting plasmid pAAV/Ad (6) into human embryonic kidney (293) cells infected with an E1-deleted adenovirus as described by Fisher et al. (7). pAAV-F.IX was derived from psub201 (6) and contains the cytomegalovirus (CMV) promoter/enhancer, the hF.IX coding sequence including a 1.4-kb fragment of intron I (13), and the simian virus 40 polyadenylylation signal, flanked by AAV inverted terminal repeat sequences. The size of pAAV-F.IX is 8.34 kb. The AAV rep and cap gene functions were supplied in trans by pAAV/Ad. E1-deleted adenovirus contained a lacZ or alkaline phosphatase reporter gene to trace potential contamination of rAAV stocks with helper virus. Cells were lysed 48 hr after transfection by sonication, and the released viral particles were purified by four rounds of CsCl density gradient centrifugation as described by Fisher et al. (7).
AAV-F.IX particles had a density of 1.37–1.40 g/ml. The titer of the purified AAV-F.IX was determined by slot blot hybridization using a probe specific to either the CMV promoter or intron I sequences and standards of pAAV-F.IX plasmid DNA of known concentration. The ability of AAV-F.IX to transduce cells in vitro was confirmed by transducing growing HeLa cells and measuring the concentration of hF.IX in the culture supernatant 36 hr postinfection with an ELISA specific to hF.IX (14). AAV-F.IX (1012–1013 genomes/ml) was stored at −79°C in Hepes-buffered saline, pH 7.8, including 5% glycerol.
Purified AAV-F.IX routinely lacked detectable amounts of contaminating adenovirus when analyzed by transduction of 293 cells followed by staining for alkaline phosphatase or β-galactosidase as described by Fisher et al. (7). Wild-type AAV was detected at <1 infectious unit per 109 genomes of AAV-F.IX. The assay for wild-type AAV was as described elsewhere (10).
Animal Experiments.
Mouse strains selected for intramuscular injection with rAAV were C57BL/6 (Charles River Breeding Laboratories) and B6, 129, Rag 1 (The Jackson Laboratory). Female mice (4–6 weeks old) were anesthetized with an intraperitoneal injection of ketamine (70 mg/kg) and xylazine (10 mg/kg), and a 1-cm longitudinal incision was made in the lower extremity. AAV-F.IX (2 × 1011 or 1 × 1010 vector genomes per animal in Hepes-buffered saline, pH 7.8) was injected into the tibialis anterior (25 μl) and the quadriceps muscle (50 μl) of each leg using a Hamilton syringe. Incisions were closed with 4–0 Vicryl suture. Blood samples were collected at 7-day intervals from the retro-orbital plexus in microhematocrit capillary tubes and plasma assayed for hF.IX by ELISA (vide infra). For immunofluoresence staining and DNA analysis, animals were sacrificed at selected time points, and injected and noninjected muscles were excised (as well as other tissues). Tissue was placed in OCT embedding compound, snap-frozen in liquid nitrogen-cooled isopentane for 7 sec, and immediately transferred to liquid nitrogen.
Assays for hF.IX.
Human F.IX antigen in mouse plasma was determined by ELISA as described by Walter et al. (14). This ELISA did not crossreact with mouse F.IX. All samples were measured in duplicate. Protein extracts from injected mouse muscle were prepared by maceration of muscle in PBS containing leupeptin (0.5 mg/ml) followed by sonication. Cell debris was removed by microcentrifugation, and 1:10 dilutions of the protein extracts were assayed for hF.IX by ELISA. Extracts from AAV-lacZ-injected muscle were used as negative controls. Protein concentrations were determined with the Bio-Rad assay (Bio-Rad).
Immunofluorescence Staining of Tissue Sections.
Cryosections of muscle tissue (6 μm) were fixed for 15 min in 3% paraformaldehyde in PBS, pH 7.4, rinsed in PBS for 5 min, incubated in methanol for 10 min, washed three times in PBS, and then blocked in PBS/3% BSA for 1 hr. Sections were subsequently incubated overnight with an affinity-purified goat anti-hF.IX antibody (Affinity Biologicals, Hamilton, Ontario, Canada) that was diluted 1:1,000 in PBS/1% BSA. After three washes (10 min each) in PBS/1% BSA, the secondary antibody was applied for 90 min [fluorescein isothiocyanate (FITC)-conjugated rabbit anti-goat IgG (Dako) diluted 1:200 in PBS/1% BSA]. After three additional washes sections were rinsed in distilled water, air-dried, and mounted with Fluoromount G (Fisher Scientific). All incubation steps were at room temperature, except for incubation with the primary antibody (4°C). The same protocol was applied when sections were stained with rabbit anti-human collagen IV as primary antibody (Chemicon) in a 1:500 dilution and FITC-conjugated anti-rabbit IgG (Dako) as secondary antibody. For colocalization studies, a goat anti-hF.IX antibody conjugated to FITC (Affinity Biologicals) was applied simultaneously with the anticollagen IV antibody, and rhodamine-conjugate anti-rabbit IgG (Chemicon) was used to detect collagen IV-antibody complexes. Fluorescence microscopy was performed with a Nikon FXA microscope.
Tests for Circulating Antibody Against hF.IX.
Plasma samples of C57BL/6 mice intramuscularly injected with AAV-F.IX were tested for the presence of antibodies against hF.IX using an ELISA. Microtiter plates were coated with hF.IX (1 μg/ml in 0.1 M NaHCO3, pH 9.2). Dilute plasma samples (1:16) were applied in duplicate, and antibodies against hF.IX detected with horseradish peroxidase-conjugated anti-mouse IgG (Zymed) in a dilution of 1:2,000. Buffer conditions were as described (14). Anti-hF.IX levels were estimated by comparison of absorbance values with monoclonal mouse anti-hF.IX (Boehringer Mannheim) diluted to a final concentration of 1 μg/ml. Negative controls included noninjected and AAV-lacZ-injected mice.
Western blots to demonstrate the presence of anti-hF.IX were performed as outlined by Dai et al. (1), except that a horseradish peroxidase-conjugated goat anti-mouse IgG antibody (Boehringer Mannheim) was used as secondary antibody, thereby allowing the detection of hF.IX-antibody complexes with ECL reagent (Amersham). Samples of mouse plasma were diluted 1:500.
DNA Analyses.
Total genomic DNA was isolated from muscle, liver, spleen, and heart as described for mammalian tissue by Sambrook et al. (15). PCR were carried out as previously described to amplify head-to-tail junctions of rAAV tandem repeats (10). The forward primer 005 (5′-ATAAGCTGCAATAAACAAGT-3′) anneals to the simian virus 40 polyadenylylation signal (bp position 8014–8033), and reverse primers 013 (5′-CATGGTAATAGCGATGACTA-3′) and 017 (5′-GCTCTGCTTATATAGACCTC-3′) bind to the CMV promoter (bp position 4625–4606 and 4828–4809) (see Fig. 5A). PCR products were cloned (for DNA sequence analysis) using the T/A cloning kit (Invitrogen). Southern blot hybridizations were performed using [32P]dCTP random primed labeled probes specific for the CMV promoter (for hybridization to PCR fragments) or for intron I of hF.IX as present in AAV-F.IX (for hybridization to genomic mouse DNA).
Analyses of DNA isolated from muscle injected with AAV-F.IX. (A) Diagram showing head-to-tail tandem repeats of two vector genomes of AAV-F.IX. Indicated are AAV inverted terminal repeats (ITR), CMV promoter/enhancer (CMV), hF.IX cDNA including coding sequence, and 228 bp of the 3′ untranslated region, a 1.4-kb portion of intron I, simian virus 40 polyadenylylation signal (SV40), and the junction site of the two genomes (J). A 1.2-kb EcoRV–EcoRI fragment from intron I and a 0.7-kb BglII fragment from the CMV promoter fragment were chosen as probes for Southern blot hybridization. Positions of binding sites for primers 005 (forward primer), 013, and 017 (reverse primers) are also shown. (B) Southern blot hybridization of genomic DNA isolated from muscle of Rag 1 mouse 6 weeks postinjection with AAV-F.IX. A radioactively labeled EcoRV–EcoRI fragment from intron I of hF.IX served as a probe. Lane 1, pAAV-FIX plasmid DNA (50 pg). Lanes 2 and 3, DNA isolated from muscle injected with AAV-F.IX. Lanes 4 and 5, DNA isolated from uninjected animal. Lanes 1, 2, and 4, DNA digested with EcoRV. Lanes 3 and 5, undigested DNA. Fifteen micrograms of genomic DNA per lane (lanes 2–5). DNA was separated on a 1% agarose gel before transfer onto a nylon membrane (Schleicher and Schuell). Size markers in the left margin are based on migration of a commercially available set of markers (GIBCO/BRL). (C) Southern blot hybridization of junction fragments of head-to-tail concatemers of AAV-F.IX amplified by PCR. PCR products amplified from genomic DNA using primer pair 005–013 (odd-numbered lanes) or primer pair 005–017 (even-numbered lanes) are shown. Lanes 1 and 2, Uninjected animal. Lanes 3–6, C57BL/6 mice i.m.-injected with AAV-F.IX. Lanes 7–10, Rag 1 mice i.m.-injected with AAV-F.IX. PCR products were from tibialis anterior (lanes 3, 4, 7, and 8) or quadriceps (lanes 5, 6, 9, and 10) muscle DNA. Lanes 11 and 12, PCR products from cell line 10–3.AV 5, which contains at least two monomer copies of integrated AAV-lacZ arranged head-to-tail (10). Note that the sizes of the major PCR products for lanes 11 and 12 are 0.8 and 1 kb, respectively. PCR products were separated on a 2% agarose gel before blotting onto a nylon membrane. A 0.7-kb BglII fragment from the CMV promoter served as a probe. Genomic muscle DNA had been isolated 6 to 8 weeks postinjection.
Expression of hF.IX in Immunocompetent Mice.
The rAAV vector chosen for in vivo experiments contains the hF.IX cDNA including a portion of intron I under transcriptional control of the CMV immediate early gene promoter/enhancer and simian virus 40 polyadenylylation signal. This expression cassette is flanked by AAV inverted terminal repeat sequences and completely lacks AAV protein coding sequences (see Materials and Methods). After intramuscular injection of AAV-F.IX into immunocompetent C57BL/6 mice, hF.IX was detected either transiently or not at all in the plasma of injected animals (Fig. 1). When the same plasma samples were tested for antibodies against hF.IX, a strong antibody response was seen in all injected animals starting at day 11 postinjection (Fig. 2 A and B and data not shown). High levels of circulating antibody persisted for the duration of the experiment. However, protein extracts from injected muscles (tibialis anterior and quadriceps) from animals sacrificed 1 month postinjection revealed the presence of 1.8–2.1 ng of hF.IX per mg of tissue (40–50 ng of hF.IX per mg of protein). The presence of hF.IX in muscle tissues was confirmed by immunofluorescence studies on tissue sections. Fig. 3 B–D shows the expression of hF.IX in muscle fibers of C57BL/6 mice 3 months postinjection. Note that F.IX is present not only in the muscle fibers themselves, but in the interstitial spaces between the fibers as well, where it appears to accumulate. Interestingly, this staining pattern was identical to that seen with a polyclonal antibody against human collagen IV, which also stained the interstitial space (Fig. 4B). Colocalization of the signals for F.IX and collagen IV was confirmed by simultaneous staining with two different fluorescence labels (Fig. 4C). Collagen IV recently has been identified as a binding protein for hF.IX (16). Factor IX was not detected in uninjected muscle (Fig. 3A) or muscle injected with AAV-lacZ (data not shown).
Plasma concentration of hF.IX in experimental mice as a function of time after intramuscular injection with AAV-hF.IX. ▵, C57BL/6 mice after i.m. injection of 2 × 1011 vector genomes/animal. □, Rag 1 mice after i.m. injection of 1 × 1010 vector genomes/animal. ○, Rag 1 mice after i.m. injection of 2 × 1011 vector genomes/animal. Each line represents an average of four animals with error bars denoting SD.
Circulating antibody against hF.IX as a result of i.m. injection of AAV-F.IX in C57BL/6 mice. (A) Time course of anti-hF.IX antibody concentration in plasma after injection with 2 × 1011 vector genomes/animal (n = 3) as determined by ELISA using mouse monoclonal anti-hF.IX (Boehringer Mannheim) as a standard. Each line represents an individual animal. Note that the units on the y axis represent an estimate only, because of probable differences in affinity for hF.IX between the mouse monoclonal used as the standard and the antibodies present in the serum of injected mice. (B) Western blot demonstrating the presence of antibodies against hF.IX in plasma of C57BL/6 mice after i.m. injection. Lane 1, Animal injected i.m. with AAV-lacZ, day 18 postinjection. Lane 2, Animal injected i.m. with rAAV-hF.IX (14), day 20 postinjection. Lanes 3–10, Animals injected i.m. with AAV-F.IX. Lanes 3–7, days 11, 18, 32, 54, and 60 postinjection (same animal). Lanes 8–10, day 18 postinjection (different animals).
Immunofluorescence staining (with antibody to hF.IX) of tibialis anterior muscle of C57BL/6 mice. (A) Uninjected muscle. (B–D) Muscle 3 months postinjection with AAV-F.IX (3.3 × 1010 vector genomes per injection site). (×200.)
Immunofluorescence staining of muscle sections of tibialia anterior muscle of C57BL/6 mice injected with AAV-F.IX 3 months earlier. Muscle sections were stained simultaneously with FITC-conjugated antibody against hF.IX and a rhodamine-conjugated antibody complex against collagen IV. (A) Fluorescence of FITC (green) showing the presence of hF.IX in muscle fibers and interstitial spaces. (B) Fluorescence of rhodamine (red) showing collagen IV in the extracellular matrix of muscle fibers. (C) Simultaneous excitation of both fluorescence tags. Note the presence of a yellow signal in the interstitial spaces. (×400.)
Inflammation or extensive tissue damage, as described for skeletal muscle injected with recombinant adenovirus (1, 3, 11), was not observed in any of the tissue sections discussed above nor in sections analyzed by hematoxylin/eosin staining (data not shown).
Expression of hF.IX in Immunodeficient Mice.
AAV-F.IX was also delivered to muscles of Rag 1 mice, which are homozygous for a mutation in the recombinase activating gene 1. These animals are therefore functionally equivalent to severe combined immunodeficiency mice and do not produce mature B or T cells. A dose of 2 × 1011 vector genomes per animal resulted in stable expression of hF.IX in mouse plasma (Fig. 1). hF.IX was first detectable by ELISA in the second week after the injection and rose gradually thereafter. Plasma levels reached a plateau 5 to 7 weeks postinjection at 200 to 350 ng of hF.IX per ml of mouse plasma. This level was maintained for the duration of the experiment (6 months postinjection). When a total of 1 × 1010 vector genomes was injected, expression was 3- to 4-fold lower, but still reached therapeutic levels (>100 ng/ml) for some animals (Fig. 1).
Analysis of DNA Introduced into Skeletal Muscle.
Genomic DNA from injected muscle tissue was isolated 6 to 8 weeks postinjection. The plasma level of hF.IX at the time of sacrifice was 225 ng/ml. The presence of introduced vector DNA was demonstrated by digestion with EcoRV, which releases a 1.8-kb fragment from the vector construct including the entire 1.4-kb intron I sequence. A probe specific to intron I hybridized to this fragment (Fig. 5B, lanes 1 and 2) and did not crosshybridize to mouse DNA from an uninjected animal (Fig. 5B lanes 4 and 5). rAAV genome copies per diploid mouse genome can be estimated based on the relative strengths of the signals in lanes 1 and 2, and are ≈0.9 rAAV genomes/diploid mouse genome for injected muscle. Undigested DNA (Fig. 5B, lane 3) showed a hybridization signal in the high molecular mass DNA. Furthermore, PCR primers designed to amplify junction sequences of head-to-tail concatemers of rAAV present in transduced cells (Fig. 5A) successfully amplified such sequences from muscle DNA isolated from AAV-F.IX-transduced tissue (tibialis anterior and quadriceps of immunodeficient and immunocompetent animals). The PCR products were visualized by Southern blot hybridization with a probe specific to the CMV promoter/enhancer (Fig. 5C, lanes 3–10). Primer pair 005–013 produced fragments that were 1.0 kb and smaller; primer pair 005–017 amplified fragments that were 1.2 kb and smaller. As expected, these PCR reactions resulted not in distinct bands of the sizes noted above, but rather in a series of amplification products with a maximum size as predicted, because of imprecise joining of AAV genomes present in these tandem repeats (10, 17). The imprecise joining results from variable deletions of inverted terminal repeat sequences at the junction sites as confirmed by DNA sequencing of cloned PCR products (data not shown). Similar analysis of DNA derived from noninjected muscle, heart, spleen, and liver disclosed no evidence for the presence of AAV-F.IX genomes in these tissues (data not shown).
The establishment of an experimental basis for gene therapy of hemophilia B has been hindered by low levels of transgene expression when retroviral vectors are used (18) or by transient expression due to an immune response to the viral vector in the case of adenovirus (1, 14, 19). Recent studies have demonstrated that rAAV vectors can direct persistent expression of reporter genes in mucle fibers of immunocompetent animals (10–12). Why efficient transduction is achieved in these postmitotic cells is unclear. Nevertheless, we sought to exploit this observation to determine whether therapeutic levels of F.IX could be achieved in the circulation of experimental animals after intramuscular injection of a rAAV vector expressing hF.IX. Our studies document that it is possible to achieve therapeutic levels of F.IX using this strategy.
Initial experiments in immunocompetent mice demonstrated that, despite high levels of gene transfer and stable expression of F.IX in injected tissue, it was not possible to detect significant amounts of hF.IX in the circulation, because the animals had developed high-titer antibodies against the circulating foreign protein. [This finding contrasted sharply with our previously reported experience (14), and that of others (20) in which intravenous injection of an adenoviral vector expressing hF.IX did not trigger formation of neutralizing antibodies against hF.IX.] When injection of AAV-F.IX was carried out in immunodeficient (Rag 1) mice, all animals achieved therapeutic levels of hF.IX, in the range of 200–350 ng/ml. These levels, which represent 4–7% of normal circulating levels in plasma, are well within a therapeutic range, and demonstrate that the approach is a feasible one from the standpoint of treating hemophilia. The plasma protein levels achieved here are of particular note because they are crucial to the success of this strategy and because they are considerably higher than those noted in a recent report in which erythropoietin was used as the transgene in a rAAV vector [maximal levels of 750 milliunits/ml, which is equivalent to ≈5 ng/ml of erythropoietin using a specific activity of 119,000 units/mg of protein (12)].
The studies presented here provide some novel insights into the biology of F.IX expression in muscle tissue. Kurachi and colleagues (21) have previously carried out detailed characterization of hF.IX expressed in mouse primary myoblasts and have shown based on analysis of purified hF.IX that the secreted material has full biological activity in a one-stage clotting assay (specific activity 95–125% of plasma-dervied F.IX), is properly processed at the N terminus, and has γ-carboxyglutamic acid content (necessary for biological activity) comparable to that of plasma-derived F.IX. An interesting observation reported earlier by these same investigators was that, after transplantation of transduced myoblasts, the plasma levels of hF.IX were only ≈22% of predicted levels (based on in vitro F.IX synthesis rates in the transduced myoblasts). In our studies, muscle sections from injected tissue showed a characteristic staining pattern, with F.IX localized to some extent intracellularly, but also found extensively in the interstitial spaces between muscle fibers. Although one might expect to see some degree of extracellular staining for a secreted protein such as F.IX, we had not anticipated the finding seen here, specifically what appeared to be a concentration of F.IX in the interstitial spaces. A recent report (16) presents compelling evidence that collagen IV acts as a specific receptor for F.IX. The authors demonstrate that hF.IX binds to collagen IV in the extracellular matrix of endothelial cells in a specific and saturable manner, with a Kd in the nanomolar range. We hypothesized that collagen IV in the basement membrane surrounding muscle fibers might explain the staining pattern seen in the F.IX immunofluorescence studies of muscle tissue. Immunostaining with antibodies to human collagen IV confirmed that the interstitial spaces were indeed rich in this protein. This finding is of interest not only as it relates to the staining pattern seen for F.IX, but also because it may at least partially account for the previously reported finding of low efficiency of transfer of muscle cell-synthesized F.IX into the circulation. Clearly, however, the trapping of F.IX in the interstitial spaces by collagen IV, if it occurs, is not an insuperable obstacle, as the experiments in Rag mice demonstrate.
The time course of expression of hF.IX in the plasma of injected Rag 1 mice is of interest; it allows a quantitative assessment of a trend that is apparent in studies carried out with rAAV-lacZ (7, 22). The absence of expression initially, followed by a slow rise in levels of expression, has been attributed to the necessity for, and the slow rate of, conversion of single-stranded AAV genome to high molecular mass double-stranded DNA. The time course for this conversion in transduced muscle fibers has been documented (10). The point at which single-stranded vector DNA is no longer detectable is reached between day 30 and day 64 postinjection. In the experiments described in this report, circulating levels of F.IX reach a plateau between week 5 and week 7 after injection with rAAV-F.IX. Whether the binding of F.IX to collagen IV in the interstices of muscle fibers further slows the rise cannot be assessed from these data; however, the existence of two F.IX variants with altered affinity for collagen IV (F.IX K5A, no binding to collagen IV; F.IX K5R, Kd 6-fold lower than wild-type F.IX) should allow this hypothesis to be tested (16, 23).
A comparison of the time course of expression of F.IX in the Rag 1 mice and the time course of appearance of antibodies in the C57BL/6 mice helps to explain the data in Fig. 1, the time course of expression of F.IX in the C57BL/6 (immunocompetent) mice. In the first week after injection, no F.IX is detected in plasma even in the Rag 1 mice. Levels of protein expression required to induce antibody formation, however, are quite low, and indeed antibodies are first detected by ELISA (see Fig. 2A) 11 days after injection. The Western blot assay is somewhat less sensitive but documents what appears to be a rising antibody titer beginning 18 days after injection. Thus in the immunocompetent animals, the absence of expression at initial time points is a result of the biology of rAAV expression in muscle, whereas the subsequent absence of detectable F.IX results from the production of antibodies to the foreign protein. The data of Kessler et al. (12) suggest that an immune response to a muscle-expressed transgene is avoided if the expressed protein is autologous; this point will require additional exploration.
The PCR studies presented here (Fig. 5C) demonstrate the presence of head-to-tail concatemers of AAV-F.IX DNA. Whereas head-to-head and tail-to-tail arrangements of AAV genomes can occur during viral replication (24), head-to-tail arrays are more typically associated with AAV that has been integrated into the chromosomal DNA of the transduced cell during latent infection (17, 25, 26). Southern blot data on undigested rAAV-injected muscle cell DNA show that the rAAV DNA derived from host cell genomic DNA 6 weeks after injection is present as a high molecular mass species. The higher signal intensity seen with the restricted DNA (Fig. 5B, compare lanes 2 and 3) likely results from an unmasking effect when the fragments are separated from the bulk of genomic DNA (11). This finding, the presence of a hybridization signal for high molecular mass DNA, is, like the PCR data, consistent with integrative events occurring during transduction. Cloning of junction fragments between chromosomal and vector DNA would be necessary to confirm this interpretation. The data are also consistent with the presence of the DNA as a high molecular mass episomal form; this remains a formal possibility.
Detailed dose–response studies have not yet been carried out, but the data presented in this study may at first suggest a nonlinear response, because mice injected with 2 × 1011 vector genomes had plasma hF.IX levels in the range of 200–350 ng/ml, whereas those receiving a 20-fold lower dose still achieved levels in the range of 50–100 ng/ml. Analysis of the immunofluorescence studies provides some insight into this observation, because the overall appearance of the sections stained for transgene expression is similar, whether a lower (1 × 109 genomes per injection site) or higher (3.3 × 1010 genomes per site) dose is injected (data not shown). Transduction is probably limited by the distance the viral vector can diffuse from the injection site; thus an increase in dose without an increase in the number of injection sites will have only a limited effect on plasma levels of the transgene.
The findings presented here have several implications for development of gene therapy protocols for patients with hemophilia B. First, the levels of F.IX expression obtained here are adequate to achieve a therapeutic effect if efficient scale-up of rAAV production can be achieved. Second, it is clear from these data that multiple intramuscular injection sites will be required; because muscle tissue is abundant this is not an obstacle to treatment with this strategy. The time course of expression documented here is quite different from that seen with adenoviral vectors expressing hF.IX, where therapeutic levels are achieved almost immediately (14, 19). In the case of AAV-F.IX, the gradual rise in plasma F.IX levels over a period of weeks means that patients will need to be covered with F.IX concentrates for the period immediately surrounding the invasive intramuscular injections. The t1/2 of the exogenously administered F.IX in humans is only ≈15 hr; thus plasma F.IX levels will return to baseline before they begin to rise from expression of the transgene, facilitating analysis of results. Finally, data in the literature (12) suggest that expression from muscle tissue transduced with rAAV is persistent for long periods if cross-species boundaries are not transgressed. Thus, administration of rAAV vectors expressing hF.IX to patients with hemophilia B should be a feasible strategy for treatment of the disease.
The assistance of the Vector Core and of Ravindra Pathak in the Cell Morphology Core of the Institute for Human Gene Therapy at the University of Pennsylvania is gratefully acknowledged. This work was supported by National Institutes of Health Grants R01 HL53668 and P50 HL54500 to K.A.H.
↵§ To whom reprint requests should be addressed at: Abramson Research Center, Room 310A, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA, 19104. e-mail high{at}email.chop.edu.
Kenneth M. Brinkhous, University of North Carolina School of Medicine, Chapel Hill, NC
F.IX,
blood coagulation factor IX;
hF.IX,
human F.IX;
FITC,
fluorescein isothiocyanate;
AAV,
adeno-associated virus;
rAAV,
recombinant AAV;
CMV,
Accepted April 1, 1997.
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You are going to email the following Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus
Roland W. Herzog, J. Nathan Hagstrom, Szu-Hoo Kung, Shing Jen Tai, James M. Wilson, Krishna J. Fisher, Katherine A. High
Proceedings of the National Academy of Sciences May 1997, 94 (11) 5804-5809; DOI: 10.1073/pnas.94.11.5804

redpajama_set_name: RedPajamaCommonCrawl


text:
Truth Vigilantes and other short notes
The most clueless post of the week came from the NYT public editor Arthur Brisbane: Should the Times Be a Truth Vigilante? Brisbane was
looking for reader input on whether and when New York Times news reporters should challenge "facts" that are asserted by newsmakers they write about.
So if a "newsmaker" says the sky is green, should the Times let that stand? or explain to its readers that the sky is actually blue?
That post drew 327 comments and countless responses from bloggers and other pundits, almost unanimously (except for National Review) saying: If you have to ask that question, the Times is in worse trouble than we thought.
Brisbane wrote a follow-up claiming that we had all misunderstood the question, which prompted another avalanche of responses saying that we understood it perfectly.
Greg Sargent sums up current practice, which is to print a fact-check column once (maybe), but not reference it when a false claim gets repeated again and again. Result: "any Times customer reading [the false claims] comes away misled."
Glenn Greenwald translates newsmaker to mean "those who wield power within America's political and financial systems" and points out that critics of the newsmaking elite get a different treatment: "their statements are subjected to extreme levels of skepticism in those rare instances when they're heard at all."
Jay Rosen gives a long-term perspective:
Something happened in our press over the last 40 years … the drift of professional practice over time was to bracket or suspend sharp questions of truth and falsehood in order to avoid charges of bias, or excessive editorializing. Journalists felt better, safer, on firmer professional ground–more like pros–when they stopped short of reporting substantially untrue statements as false.
Salon's Marcus Cederstrom asks the question I've been wondering about for weeks: What if Tim Tebow were Muslim?
In all the uproar about American Marines urinating on Taliban corpses, one point hasn't gotten much attention: All the way back to George Washington, America has tried to maintain a code of honor for its troops. (We didn't always succeed, but we always tried.) Why?
Here's why: The American ideal is the citizen soldier who eventually rejoins civilized society. America's fighting men and women are not supposed to be packs of jackals that we unleash on our enemies and then forget about. They are us, and when they're done with the disagreeable job of war, we intend to welcome them home.
So when Dana Loesch says, "Come on, people, this is a war", she may think she's supporting our troops, but she isn't. By implying that barbaric behavior is normal in our military, she's undermining our soldiers' eventual re-integration into civilian life.
If this is how Loesch pictures Marines, how will she feel when an ex-Marine moves in next door or wants to marry her little sister? Or has the distance between Marines and media stars grown so great that such possibilities are unthinkable now?
While I enjoy Jon Stewart's pokes at our political system from the outside, nothing tops the way Stephen Colbert demonstrates its abusrdity from within.
When it became clear that unaccountable Super-PACs were going to dominate the 2012 election cycle, Colbert started one: Americans United for a Better Tomorrow Tomorrow. It's a stunt, but it's not just a stunt. He really raised money and put ads on TV in Iowa.
This week, Colbert demonstrated the absurdity of Super-PACs that are devoted to one candidate (but allegedly don't co-ordinate with that candidate's campaign) by transferring his Super-PAC to Jon Stewart and then announcing his own candidacy for president. Colbert and Stewart worked out their "non-cooperation" agreement on national TV.
And now, the Super-PAC has the absurd anti-Romney attack ad Mitt the Ripper on the air in South Carolina: If Romney really believes corporations are people, then he was a serial killer during his time at Bain Capital.
It was amazing to watch how quickly and effectively the Republican establishment moved to shut down criticism of Romney's "vulture capitalism". TPM's 100-seconds series captured it:
The point here seems to be that capitalism transcends good and evil. To make any moral comment on Romney's business practices is beyond the pale, and puts you on the road to Soviet Communism. Such a nihilistic argument is pretty weird for a party that claims to be the natural home of American Christians.
Dahlia Lithwick: "If a Republican successor of Obama gets to replace both Kennedy and Ginsburg, it's fair to predict that the Roberts Court may include five or even six of the most conservative jurists since the FDR era." We wouldn't just see a loss of abortion rights, but "a jurisprudence that skews pro-business, pro-life, anti-environment, and toward entangling the church with the state."
If you haven't checked out Vi Hart's YouTube channel, you're missing the Internet's best example of charming geekiness.
It's always important on MLK Day, to remember just how radical King was. He didn't promote a vague be-nice message, but took outside-the-current-mainstream stands on major issues.
By weeklysift, on January 16, 2012 at 11:50 am, under Short Notes. Tags: 2012 election, media, Republicans, war. 1 Comment
« Inventing the Narrative
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By Profit and Property, or People? « The Weekly Sift on January 16, 2012 at 12:32 pm
[…] Truth Vigilantes and other short notes. The Times gets an earful from its readers. Defending corpse desecration doesn't support our troops. What if Tebow were Muslim? Colbert's Super-PAC demonstrates the absurdity of our campaign-finance system. The Republican establishment shuts down criticism of Romney. The charming geekiness of Vi Hart. And more. […]


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Application Procedure for NLNG Prize for Science – 2019 [The Prize is $100,000]
Filed in Scholarships	| By NGSchoolz Staff | Last Modified: 4 months ago
How To Apply for 2019 Nigeria Liquefied Natural Gas, NLNG Prize for Science is here: The Nigeria Prize for Science 2019 application process has started. Interested applicants should read through the 2019 Science prize details below. The winner/s would receive an award of one hundred thousand US dollars ($100, 000.00).
Nigeria Liquefied Natural Gas (NLNG) Limited invites entries for The Nigeria Prize for Science, in line with its vision of helping to build a better Nigeria. This annual prize for Science is endowed by Nigeria LNG Limited (NLNG) to recognise outstanding scientific achievements by Nigerians and non-Nigerians alike for advancing scientific solutions to prescribed problems afflicting Nigeria, as captured by the theme of the year. The winner(s) would receive an award of one hundred thousand US dollars ($100, 000.00).
The Nigeria Prize for Science Theme.
The theme for the 2019 competition is: Climate Change: Erosion, Drought and Desertification.
Entries are therefore invited from researchers for works that contribute to dealing with issues arising from Climate Change especially Erosion, Drought and Desertification-especially from the Nigerian perspective.
The Nigeria Prize for Science Eligibility.
The award is open to all Nigerians and non-Nigerians involved in the application of science to proffer a novel solution to remediate the impact of Climate Change especially Erosion, Drought and Desertification. These works can be cumulative in nature covering all of these of areas or specific to any of the topics listed.
The work should be of outstanding merit and should have advanced the frontiers of knowledge and/or provide an innovative solution in the area of Climate Change.
The submission for consideration must be original and must indicate the specific area of merit; and all submissions must relate to that particular area.
The submission for award must not be under consideration for any other award.
All material in support of the entry must be submitted within the time stipulated.
Entries, including the supporting documents, must be submitted in six (6) copies, for hard copies.
The Nigeria Prize for Science Panel of Judges & Advisory Board.
A Panel of Judges shall be appointed for The Nigeria Prize for Science by the Advisory Board.
The appointment of judges shall, as far as possible, reflect and represent a multi-disciplinary approach relevant to the theme. Persons appointed as judges are those who have wide experience, peer recognition, good public image and command respect nationally and internationally.
The decision of the process shall be final.
Professor Alfred A. Susu, FAS, NNOM – Chairman
Professor Barth Nnaji, FAS, CON, NNOM – Member
Dr. (Mrs) Nike Akande, CON – Member
Professor Michael Adikwu, FAS – Member
The Nigeria Prize for Science Submission Procedure.
Applicants must complete and submit their entries online accompanied by an application form obtainable online from the NLNG website.
Hard copy submissions are also acceptable but must be accompanied by the printed copy of the completed application form.
As the intention is to recognise the most relevant and effective solution to specific Nigerian problems, works of collaboration by two or more persons are also welcome.
Only one entry per contestant(s) is permitted per competition year.
No entry previously submitted for this competition may be considered at a later date.
Entries not submitted by the stated deadline and according to stated conditions shall not be considered.
Members of the Advisory Board or Panel of Judges or their relatives are not allowed to enter their works for the Science Prize during their year of service as well as the following year.
NLNG staff or their family members are ineligible to enter for the prize.
The prize will be awarded for no other reason than excellence
How To Enter The Nigeria Prize for Science.
Entries shall be sent to:
The Nigeria Prize for Literature
External Relations Division
Nigeria LNG Limited
Intels Aba Road Estate
Km 16 Port Harcourt-Aba Expressway
RM.B 5660, Port Harcourt
Rivers State, Nigeria.
nigeriaprizeforscience@nlng.com
4th Floor, Heron House
10 Dean Farrar Street
London, SW1H 0DX.
All entries must be received by May 03, 2019. Late entries will not be entertained.
FCT Scholarship Application Forms for 2016/17 Award Session [How To Apply]
NLNG Scholarship Award For Nigerian Students
Centre for the Right to Health (CRH) Student Nurse Essay Competition 2018
Apply for NNPC/Chevron JV National University Scholarship 2018/2019
Apply For Total Postgraduate Scholarship – 2017/18
Apply For Justina Ejelonu Memorial Scholarship for Nurses
Tags: NLNG, NLNG Prize for Science
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Even if you are halfway around the world you still gotta eat, right? Some even go as far as to say they travel just to eat different things! So get exploring to see the best of cuisines, the strangest food items, incredible beverages, F&B anecdotes- basically, the world is your banquet!
Why is Japanese Cuisine Healthy?


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Drug & Alcohol Rehab in Washington
There's help for people recovering from addiction in the state of Washington. You can find treatment and take your first steps on the path toward recovery today.
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News In Washington
Current Drug Trends
Washington's Meth Crisis Enters a Deadly New Phase
Initiatives, Awareness & Support
Why Drinking and Driving Is Such a Big Problem in Washington
Laws, Regulations & Insurance
How Marijuana Laws Have Affected Washington
Common Drug Addictions Treated in Washington
More people in Washington sought treatment for heroin addiction than any other drug in 2015. Alcohol in combination with another drug was the second-most-common addiction treated that year, followed by marijuana.
The total number of heroin treatment admissions has grown during each of the past three years, accounting for almost a quarter of all treatment admissions in 2015. The number of amphetamine admissions increased each year from 2013 to 2015.
Treatment Admissions by Substance (2015)
22.9% 7,982
Alcohol & another drug
9.9% 3,453
1.6% 566
0.3% 91
Why Choose Rehab in Washington?
Washington is home to a vast number of drug rehabilitation facilities, mental health organizations and support groups. You can find help for addiction in the Evergreen State. From Vancouver to Bellingham, support systems are in place to aid in your recovery.
How Do Washington Facilities Rank?
Total Number 10th (510)
Treats co-occurring disorders 15th (163)
Provides residential detox 13th (21)
Provides outpatient detox T-22nd (21)
Provides residential treatment 17th (63)
Provides outpatient treatment 8th (395)
Accepts private insurance 5th (403)
Accepts Medicare 23rd (89)
Accepts Medicaid 8th (261)
Accepts payments on a sliding scale 8th (274)
No charge for clients who cannot pay 10th (195)
Drug Abuse Trends in Washington
Similar to national trends, the state of Washington has experienced a sharp increase in opioid-related criminal activity, drug overdoses and addiction treatment admissions. Alcohol and marijuana are among the most popular substances of abuse, followed by opioids and amphetamines.
After remaining near or below the national average from 2009 to 2012, the percent of individuals who abused an illicit drug in Washington climbed above the national average. Washington's heavy alcohol consumption is slightly higher than the national average.
Past-Year Illicit Drug Abuse or Dependence Among Washington Adults
Heroin and Opioid Use Increase
Opioid abuse and addiction increased drastically in Washington during the last decade. From 2002 to 2013, crime lab evidence that tested positive for an opioid increased 85 percent. The number of treatment admissions for opioid addiction increased 197 percent, and the number of deaths involving opioids increased by 31 percent. In total, there were 6,668 opioid-related deaths from 2002 to 2013.
Learn more about substance abuse trends in Washington.
Similar to national trends, the abuse of prescription painkillers spiked between 2008 and 2010, but heroin abuse continued to increase through 2013, the more recent year that data is available.
Rate of Washington Opioid Increase
Treatment Admissions
Crime Lab Cases
Rate of Deaths
Rate of Treatment Admissions:
Rate of Crime Lab Cases:
Rate of Deaths:
Washington Youth Survey
Overall, alcohol abuse among high school seniors in Washington has steadily decreased since 2004. The number of seniors who reported drinking alcohol in the month prior to the state's youth survey decreased from 43 percent in 2004 to 33 percent in 2014. The percentage of students who reported ever drinking alcohol or binge drinking has also declined during the last decade.
Marijuana use among high school seniors increased from 19 percent in 2004 to 27 percent in 2014. The percentage of teens who smoked cigarettes or used prescription painkillers declined during the decade.
About one-third of Washington high school seniors admitted to drinking alcohol in the past 30 days in 2014
Almost one-fifth of high school seniors admitting to binge drinking in 2014.
A total of 27 percent of high school seniors said they consumed marijuana in the past 30 days in 2014.
About 13 percent of high school seniors reported smoking cigarettes in the past 30 days in 2014.
Prescription Painkillers
A total of nine percent of high school seniors said they abused a prescription drug in the past 30 days in 2014.
Top Cities to Rehab in Washington
Government Prevention and Treatment Efforts
In Washington, the Department of Social and Health Services oversees behavioral health programs, funding and prevention initiatives. The department provides some type of care to 2.7 million of the state's 7 million residents each month. One of its strategic goals is to be a national leader in mental health services including treatment, recovery and prevention services.
The Division of Behavioral Health and Recovery was created in 2009 to oversee services for all mental health disorders. The division of the Department of Social and Health Services provides funding, training and technical expertise for local health care providers and treatment facilities.
Behavioral Health Advisory Council
The Washington State Behavioral Health Advisory Council brings citizens, providers, private and public parties and government officials together. The council advises the Division of Behavioral Health and Recovery on activities including operations, funding, planning and evaluation of initiatives.
The DBHR supports long-term, community-based prevention programs through its Community Prevention and Wellness Initiative. The division partners with local governments and school districts to provide funding and expertise for programs in the state's 39 counties and nine educational districts.
SBIRT Primary Care Integration Project
The Screening, Brief Intervention, and Referral to Treatment (SBIRT) Primary Care Integration project trains primary health care providers to identify patients who abuse drugs and help prevent or treat addiction. The program serves four counties in Washington and about 96,000 citizens.
Mental Health Promotion Project
The Mental Health Promotion Project provides federal funding to nationally recognized tribes for mental health projects. The goal of the project is to reduce barriers to mental health by reducing discrimination and promoting equal access to education, employment, housing and health services.
College Coalition for Substance Abuse Prevention
The College Coalition for Substance Abuse Prevention comprises state representatives, business partners and mental health professionals from several colleges and universities in Washington. The organization supports professional development and technical assistance for drug abuse prevention efforts throughout the state.
Peer Support Program
Washington's Peer Support Program, managed by the Office of Consumer Partnerships, certifies individuals in recovery, so they can provide certified peer support for other individuals receiving mental health services. The counselors use their personal experiences to help others in recovery.
Student Assistance Prevention-Intervention Services Program
The Office of the Superintendent of Public Instruction runs the Student Assistance Prevention-Intervention Services Program. The program provides tobacco, alcohol and other drug abuse prevention and intervention services in public schools. Services include screening, counseling, case management and referral programs.
Washington Healthy Youth Coalition
The Washington Healthy Youth Coalition works to decrease underage drinking and marijuana use in communities throughout the state. The coalition maintains and promotes an educational website for parents, implements statewide education campaigns and awards grants to community groups.
Spring Youth Forum
Sponsored by the Department of Social and Health Services and the Department of Health, the Spring Youth Forum recognizes youth prevention groups and provides a networking opportunity for youth from across the state. Youth can attend training workshops and share success stories at the forum.
Washington State Tobacco Quitline
The state of Washington supports the Tobacco Quitline which connects individuals suffering from tobacco addiction with a "quit coach" who can answer questions, provide educational materials and develop a quit plan. Residents also have free access to the SmartQuit app, an evidence-based smoking cessation program.
Northwest High Intensity Drug Trafficking Area
Several counties in Washington are part of the U.S. Drug Enforcement Administration's Northwest High Intensity Drug Trafficking Area. Federal, state and local law enforcement agencies work together to decrease drug trafficking and other drug-related crimes in the state.
The state of Washington began allowing licensed retailers to sale marijuana to residents and out-of-state visitors ages 21 and older in July, 2014. Residents may also grow marijuana and use it recreationally in their home.
Individuals cannot consume marijuana in retail stores, and they can't consume a marijuana product in view of the general public. Marijuana can't be taken out of the state, and driving under the influence of marijuana remains illegal in Washington. Businesses — such as hotels, motels and inns — have the authority to ban marijuana consumption on their premises.
Addiction treatment centers throughout Washington can help individuals suffering from marijuana addiction. Various nonprofit and community-based organizations throughout the state continue to advocate against marijuana consumption, especially among youth.
Statewide Community Resources
Several community-based or nonprofit organizations in Washington strive to prevent drug abuse and help individuals suffering from drug addiction.
University of Washington Alcohol and Drug Abuse Institute
The University of Washington's Alcohol and Drug Abuse Institute conducts research and develops reports on drug abuse trends in the state. The institute's Center for Opioid Safety Education provides opioid-related educational information and technical assistance to prevention and intervention organizations in the state.
Washington Association for Substance Abuse & Violence Prevention
The Washington Association for Substance Abuse & Violence Prevention comprises advocates for drug abuse prevention from across the state. The organization advocates for prevention efforts, supports existing efforts, encourages sustainable programs, inspires collaboration and attempts to sway public policy.
Washington State Prevention Summit
The Washington State Prevention Summit is an annual event that brings members of the drug prevention community together to evaluate previous efforts, discuss new strategies and to collaborate. Parents, teachers, law enforcement, treatment providers, policymakers and a variety of other individuals attend the summit.
National Organization on Fetal Alcohol Syndrome Washington Affiliate
The National Organization on Fetal Alcohol Syndrome affiliate in Washington is a nonprofit that builds partnerships with community coalitions, helps coordinate public outreach campaigns and develops media campaigns. The organization helps unify families, community members and health professionals to raise awareness about the dangers of drinking alcohol while pregnant.
Youth 'N Action
Youth 'N Action empowers young adults ages 14 – 24 to advocate for overall health and wellness in Washington. The organization helps youth build leadership skills and provide support for their peers. Youth 'N Action also advocates for policy changes to prevent youth from consuming drugs and alcohol.
Previously called the Washington Coalition to Reduce Underage Drinking, the Washington Youth Coalition comprises 27 government agencies and organizations in Washington. The organization's mission is to reduce underage alcohol and marijuana use in the state by supporting related policies and implementing statewide media campaigns.
Take Back Your Meds
Take Back Your Meds consists of 270 health organizations, government agencies and community groups that support medicine take-back programs. The organization's goal is to decrease the availability of addictive drugs on the street by developing a statewide drug take-back program funded by pharmaceutical companies.
Find a Support Group in Your Area
There are thousands of support group meetings throughout Washington.
Select an Area to See Meetings and Times
ADAI. (2014). Healthy Youth Survey Fact Sheet. Retrieved from http://adai.uw.edu/wastate/HYS/2014%20Washington%20State.pdf
CCSAP. (2016). About. Retrieved from http://ccsap.wsu.edu/about/
CCSAP. (2016). Mission. Retrieved from http://ccsap.wsu.edu/mission/
Center for Opioid Safety Education. (2016, January) Home. Retrieved from http://stopoverdose.org/cose/index.htm
NOFAS Washington State. (2008). Mission/Vision. Retrieved from http://www.nofaswa.org/mission/
Office of National Drug Control Policy. (n.d.). Northwest HIDTA. Retrieved from https://www.ncjrs.gov/ondcppubs/publications/enforce/hidta2001/nw-fs.html
Spring Youth Forum. (n.d.). Home. Retrieved from http://springyouthforum.org/
State of Washington Office of Superintendent of Public Instruction. (n.d.). Prevention/Intervention. Retrieved from http://www.k12.wa.us/PreventionIntervention/
Substance Abuse and Mental Health Services Administration. (2013). National Survey of Substance Abuse Treatment Services (N-SSATS): 2013. Retrieved from http://wwwdasis.samhsa.gov/dasis2/nssats/2013_N-SSATS_National_Survey_of_Substance_Abuse_Treatment_Services.pdf
Substance Abuse and Mental Health Services Administration. (2015). Behavioral Health Barometer Washington, 2014. Retrieved from http://www.samhsa.gov/data/sites/default/files/State_BHBarometers_2014_2/BHBarometer-WA.pdf
Substance Abuse and Mental Health Services Administration. (n.d.). Substance Abuse Treatment Admissions by Primary Substance of Abuse, According to Sex, Age Group, Race, and Ethnicity. Retrieved from http://wwwdasis.samhsa.gov/webt/quicklink/WA14.htm
Take Back Your Meds. (n.d.). About Us. Retrieved from http://www.takebackyourmeds.org/about/about-the-coalition
University of Washington School of Medicine. (n.d.). Youth'N Action. Retrieved from http://depts.washington.edu/pbhjp/Youth_N_Action/index.php
University of Washington. (2013, July). Overview of ADAI. Retrieved from http://adai.uw.edu/aboutadai.htm
University of Washington. (2015, April). Opioid Trends Across Washington State. Retrieved from http://adai.uw.edu/pubs/infobriefs/ADAI-IB-2015-01.pdf
WASAVP. (n.d.). Who is WASAVP. Retrieved from http://wasavp.org/who-is-wasavp/
Washington Healthy Youth Coalition. (n.d.). About Us. Retrieved from http://www.starttalkingnow.org/about-us
Washington State Department of Health. (2014, March 4). Drug Abuse and Overdose. Retrieved from http://www.doh.wa.gov/Portals/1/Documents/5500/RPF-Drg2014.pdf
Washington State Department of Health. (n.d.). SmartQuit App. Retrieved from http://www.doh.wa.gov/YouandYourFamily/Tobacco/SmartQuit
Washington State Department of Health. (n.d.). Tobacco. Retrieved from http://www.doh.wa.gov/YouandYourFamily/Tobacco
Washington State Department of Social and Health Services. (n.d.). About DBHR. Retrieved from https://www.dshs.wa.gov/bha/division-behavioral-health-and-recovery/about-dbhr
Washington State Department of Social and Health Services. (n.d.). Athena Forum. Retrieved from https://www.dshs.wa.gov/node/9053
Washington State Department of Social and Health Services. (n.d.). Behavioral Health Advisory Council. Retrieved from https://www.dshs.wa.gov/bha/division-behavioral-health-and-recovery/behavioral-health-advisory-council
Washington State Department of Social and Health Services. (n.d.). DSHS Strategic Plans. Retrieved from https://www.dshs.wa.gov/strategic-planning/dshs-strategic-plans
Washington State Department of Social and Health Services. (n.d.). Substance Abuse Prevention and Mental Health Promotion. Retrieved from https://www.dshs.wa.gov/bha/division-behavioral-health-and-recovery/substance-abuse-prevention-and-mental-health-promotion
Washington State Liquor and Cannabis Board. (n.d.). FAQs on I-502. Retrieved from http://www.liq.wa.gov/mj2015/faqs_i-502
Washington State Prevention Summit. About. (n.d.). Retrieved from #
Substance Abuse and Mental Health Services Administration. (2016, March). National Survey of Substance Abuse Treatment Services (N-SSATS): 2014. Retrieved from http://wwwdasis.samhsa.gov/dasis2/nssats/2014_nssats_rpt.pdf
Substance Abuse and Mental Health Services Administration. (2016, April 4). Substance Abuse Treatment Admissions by Primary Substance of Abuse, According to Sex, Age Group, Race, and Ethnicity Year = 2015. Retrieved from http://wwwdasis.samhsa.gov/webt/quicklink/WA15.htm
Last modified: July 22, 2019. Questions? Contact [email protected]


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News Canberra confirms 22 new coronavirus cases
12:18pm, Aug 18, 2021 Updated: 1:04pm, Aug 18
Canberra confirms 22 new coronavirus cases
Canberra has confirmed an additional 22 cases of coronavirus.
Georgie Moore
12:18pm, Aug 18
Canberra has confirmed 22 new COVID-19 cases, taking its outbreak to 67 as the virus continues its spread across ACT schools.
All of Wednesday's infections are linked to existing cases. Only four of the ACT's total cases remain a mystery.
More than 8400 tests were conducted on Tuesday and 12,500 people are in quarantine.
New cases have been identified across schools including Harrison School, St Thomas Aquinas Primary School and the University of Canberra Senior Secondary College Lake Ginninderra.
Meanwhile, 15 cases are linked to Lyneham High School. Infections have also been recorded at other campuses including the Gold Creek School.
Health Minister Rachel Stephen-Smith noted an increase in the number of young people wanting to get the AstraZeneca vaccine.
Pharmacies dolled out about 700 AstraZeneca jabs on Tuesday.
More than 30,000 AstraZeneca jabs had been spread across more than 80 GPs.
The federal government is giving ACT pharmacies and GPs an additional 10,300 doses this week.
ACT Chief Minister Andrew Barr says it's not the time to ease restrictions, particularly given Sydney's 633 new locally acquired cases and three additional deaths.
Among Canberra's outbreak is the 14-year-old daughter of Labor frontbencher Katy Gallagher.
Related: COVID chair's daughter contracts virus
The chair of the parliamentary committee looking at Australia's COVID-19 response feels angry the country has let its young people down.
"I look at Evie lying in her bed trying to fight this virus and I just can't stop the feeling that we've let her down," Senator Gallagher said.
"My son's in the next room and I'm desperately hoping he's not going to catch it."
ACT Coronavirus
COVID-positive sex worker sparks alarm in Victoria


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The Andrea Shea King Show
Politics Conservative Politics Obama Elizabeth Letchworth Congress Hillary Clinton Constitution Trump Donald Trump Obamacare Andrea Shea King News Blogtalkradiocom
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The Andrea Shea King Show « »
Lots to talk about tonight -- Franken is out, according to inside sources. Bannon kicked Mitt Romney's behind big time last night, and we've got an update from George Webb about Strokin' and his Main Squeeze.
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What will it take to defeat Donald Trump in November? In season 2 of The Wilderness, Jon Favreau looks for the path to victory in 2020 by talking to voters, strategists, organizers, and candidates in the battleground states that will decide the election.
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Congressional Dish is a twice-monthly podcast that aims to draw attention to where the American people truly have power: Congress. From the perspective of a fed up taxpayer with no allegiance to any political party, Jennifer Briney will fill you in on the must-know information about what our representatives do AFTER the elections and how their actions can and will affect our day to day lives. Hosted by @JenBriney. Links to information sources available at www.congressionaldish.com
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Home/Lifestyle/Mad House Premieres today
Mad House Premieres today
Akrobeto
A movie aimed at enlightening the public on the causes of mental illness to demystify the stigma around it, premieres at the National Theatre today.
"Mad House" is a movie by Ola Michael and Frank Garbin.
Speaking to The Spectator, director of the movie, Ola Michael, said the setting was at the Accra Psychiatric Hospital with the movie highlighting how people knowingly or unknowingly acquired mental health related illnesses and ended up at the hospital.
It also throws light on the issues at some mental health facilities which cause patients to go back to the street.
Ola Michael revealed that the movie was a total comedy with mental health education to help bring some of their issues to the front, burner.
According to him, the movie featured the likes of Ekow Smith, Big Akwes, Akroboto, Kofi Adjorlolo, Yaw Dabo, Jessica Williams, Jagga Pee, Bismark De Joke, Lawyer Nti, and General Ntatia among many others.
Talking about the challenges, he said it was all fun with both patients and health workers when shooting, however, he indicated that securing the permission to use the hospital was a difficult task.
Commenting on the current state of the movie industry, he said, it was gradually picking up, with many people showing interest in watching movies at the cinema, coupled with calls from Ghanaians in the Diaspora for local movies.
Ola Michael said, after this, there would be other premieres at the Watch and Dine Cinema in Kumasi and the Centre for National culture at Koforidua on June 22 and 23, respectively.
He added that there were movies like XXX, Captain Mahama, among others which would be released later in the year.
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"The persecution of Jews in occupied Poland meant that we could see horror emerging gradually in many ways. In 1939, they were forced to wear Jewish stars, and people were herded and shut up into ghettos. Then, in the years '41 and '42 there was plenty of public evidence of pure sadism. With people behaving like pigs, I felt the Jews were being destroyed. I had to help them. There was no choice."
You can visit the site on your own (highly recommended because you can go at your own pace, see what you want to see and have a much more meaningful experience) if you arrive before the guided tours start. Another option is to visit the Auschwitz II-Birkenau site first and then return after the guided tours finish to the first camp to avoid having to use the tour. The Auschwitz II-Birkenau site is open for visitors without the guide during the opening hours of the Memorial.
Schindler never developed any ideologically motivated resistance against the Nazi regime. However, his growing revulsion and horror at the senseless brutality of the Nazi persecution of the helpless Jewish population wrought a curious transformation in the unprincipled opportunist. Gradually, the egoistic goal of lining his pockets with money took second place to the all-consuming desire of rescuing as many of his Jews as he could from the clutches of the Nazi executioners. In the long run, in his efforts to bring his Jewish workers safely through the war, he was not only prepared to squander all his money but also to put his own life on line.
Shortly after the outbreak of war in September 1939, thirty-one-year-old Schindler showed up in occupied Krakow. The ancient city, home to some 60,000 Jews and seat of the German occupation administration, the Generalgouvernement, proved highly attractive to German entrepreneurs, hoping to capitalize on the misfortunes of the subjugated country and make a fortune. Naturally cunning and none too scrupulous, Schindler appeared at first to thrive in these surroundings. In October 1939, he took over a run-down enamelware factory that had previously belonged to a Jew. He cleverly maneuvered his steps- acting upon the shrewd commercial advice of a Polish-Jewish accountant, Isaak Stern - and began to build himself a fortune. The small concern in Zablocie outside Krakow, which started producing kitchenware for the German army, began to grow by leaps and bounds. After only three months it already had a task-force of some 250 Polish workers, among them seven Jews. By the end of 1942, it had expanded into a mammoth enamel and ammunitions production plant, occupying some 45,000 square meters and employing almost 800 men and women. Of these, 370 were Jews from the Krakow ghetto, which the Germans had established after they entered the city.
Schindler's ties with the Abwehr and his connections in the Wehrmacht and its Armaments Inspectorate enabled him to obtain contracts to produce enamel cookware for the military.[31] These connections also later helped him protect his Jewish workers from deportation and death.[32] As time went on, Schindler had to give Nazi officials ever larger bribes and gifts of luxury items obtainable only on the black market to keep his workers safe.[33] Bankier, a key black market connection, obtained goods for bribes as well as extra materials for use in the factory.[34] Schindler himself enjoyed a lavish lifestyle and pursued extramarital relationships with his secretary, Viktoria Klonowska, and Eva Kisch Scheuer, a merchant specialising in enamelware from DEF.[35] Emilie Schindler visited for a few months in 1940 and moved to Kraków to live with Oskar in 1941.[36][37]
The concept of blitzkrieg was formed by Prussian military tactics of the early 19th century, which recognized that victory could come only through forceful and swift action because of Prussia's relatively limited economic resources. It had its origins with the Schwerpunktprinzip ("concentration principle") proposed by Carl von Clausewitz in his seminal work On War (1832). Having studied generals who predated Napoleon, Clausewitz found that commanders of various armies had dispersed their forces without focused reasoning, which resulted in those forces' being used inefficiently. So as to eliminate that wasteful use of manpower, he advocated for a concentration of force against an enemy. All employment of force should have an effective concentration in a single moment, with a single action, Clausewitz argued. Clausewitz called that concentration the Schwerpunkt ("centre of gravity") where it was most dense, identifying it as the effective target for attack.
During this period, all the war's major combatants developed mechanized force theories. Theories of the Western Allies differed substantially from the Reichswehr's. British, French, and American doctrines broadly favored a more set-piece battle, less combined arms focus, and less focus on concentration. Early Reichswehr periodicals contained many translated works, though they were often not adopted. Technical advances in foreign countries were, however, observed and used in-part by the Weapons Office. Foreign doctrines are widely considered to have had little serious influence.
The first gas chamber at Birkenau was in what prisoners called the "little red house" (known as bunker 1 by the SS), a brick cottage that had been converted into a gassing facility. The windows were bricked up and its four rooms converted into two insulated rooms, the doors of which said "Zur Desinfektion" ("to disinfection"). It was operational by March 1942. A second brick cottage, the "little white house" or bunker 2, was converted and operational by June 1942.[45] When Himmler visited the camp on 17 and 18 July 1942, he was given a demonstration of a selection of Dutch Jews, a mass killing in a gas chamber in bunker 2, and a tour of the building site of the new IG Farben plant being constructed at the nearby town of Monowitz.[46]
The mass killings of Jews in the occupied Soviet territories were assigned to four SS formations called Einsatzgruppen ("task groups"), which were under Heydrich's overall command. Similar formations had been used to a limited extent in Poland in 1939, but the ones operating in the Soviet territories were much larger.[242] The Einsatzgruppen's commanders were ordinary citizens: the great majority were professionals and most were intellectuals.[243] By the winter of 1941–1942, the four Einsatzgruppen and their helpers had killed almost 500,000 people.[244] The largest massacre of Jews by the mobile killing squads in the Soviet Union was at a ravine called Babi Yar outside Kiev,[245] where 33,771 Jews were killed in a single operation on 29–30 September 1941.[246][n] A mixture of SS and Security Police, assisted by Ukrainian police, carried out the killings.[248] Although they did not actively participate in the killings, men of the German 6th Army helped round up the Jews of Kiev and transport them to be shot.[249] By the end of the war, around two million are thought to have been victims of the Einsatzgruppen and their helpers in the local population and the German Army. Of those, about 1.3 million were Jews and up to a quarter of a million Roma.[250]
Transportation between camps was often carried out in freight cars with prisoners packed tightly. Long delays would take place; prisoners might be confined in the cars on sidings for days.[190] In mid-1942 work camps began requiring newly arrived prisoners to be placed in quarantine for four weeks.[191] Prisoners wore colored triangles on their uniforms, the color of the triangle denoting the reason for their incarceration. Red signified a political prisoner, Jehovah's Witnesses had purple triangles, "asocials" and criminals wore black and green. Badges were pink for gay men and yellow for Jews.[192] Jews had a second yellow triangle worn with their original triangle, the two forming a six-pointed star.[193][194] In Auschwitz, prisoners were tattooed with an identification number on arrival.[195]
In the 1930s, Hitler had ordered rearmament programs that cannot be considered limited. In November 1937 Hitler had indicated that most of the armament projects would be completed by 1943–45.[129] The rearmament of the Kriegsmarine was to have been completed in 1949 and the Luftwaffe rearmament program was to have matured in 1942, with a force capable of strategic bombing with heavy bombers. The construction and training of motorised forces and a full mobilisation of the rail networks would not begin until 1943 and 1944 respectively.[130] Hitler needed to avoid war until these projects were complete but his misjudgements in 1939 forced Germany into war before rearmament was complete.[131]
As of right now though, it's uncertain whether Fiennes will ever get the chance to reprise his role. The only movies exploring the Wizarding World currently are the Fantastic Beasts films, which take place in 1927. Voldemort was born in 1926, so even if there would be a substantial time jump, Fiennes might be too old to play Voldemort. But at least we know that he is dedicated to the character, and that if Voldemort ever did come back, fans could count on him to jump right back into the role.
Thirty-three years after dropping out of college, Spielberg finally received a BA in Film and Video Production from his newly minted alma mater, Cal State Long Beach, in 2002. The director re-enrolled in secret, and gained his remaining credits by writing essays and submitting projects under a pseudonym. In order to pass a film course, he submitted Schindler's List as his student project. Spielberg describes the time gap between leaving school and earning his degree as his "longest post-production schedule."
Blitzkrieg it is now synonymous with shock tactics which causes the famous German maneuver to get thrown around at any situation where speed is a defining factor. A political party won the elections after scoring low in the polls… Blitzkrieg! A company launches a new product and gains tons of customers "overnight"… Blitzkrieg! The effect of the stratagem, the paralysis resulting from this lighting attack, came to signify its method.
"I suddenly see Steinlauf, my friend aged almost fifty, with nude chest, scrub his neck and shoulders with little success (he has no soap) [He] sees me and asks me severely why I do not wash. Why should I wash? Would I be better off than I am? Would I please someone more? Would I live a day longer?…. Does Steinlauf not know that after half an hour with the coal sacks every difference between him and me will have disappeared?….
As some needed to point out, this is a fictionalized account of historical events and a genuine hero. Some historical persons were combined to make one character in the book and some time frames were condensed. Oskar Schindler was a deeply flawed man, brought to greatness by living through a time of horror in a position where he could make a small, but real difference. The condensations of those true events in this book are masterful. A great book!
In order to protect the tanks, and secure the areas penetrated by the German army, motorized infantry would accompany tanks into battle. The Germans believed the only way to defeat an enemy force was to cut it off. Cutting it off required superior mobility relative to the enemy force. The introduction of mechanical means on the battlefield provided the Germans the answer to the deadlocks common in WWI. Tanks and other armored vehicles gave the German Army the ability to force the enemy to react to their new found mobility.
Under Laks' more positive leadership, the orchestra began to increase in size again. His efforts won his musicians easier work assignments and a dispensation not to play outdoors in bad weather. By the end of 1943, there were about forty members, including many Jews, from France, Germany, Poland, the Netherlands and Greece. They included Henry Meyer, Louis Bannet, and Jacques Stroumsa.
The group raced to the English Channel, reaching the coast at Abbeville and cut off the BEF, the Belgian Army and some of the best-equipped divisions of the French Army in northern France. Armoured and motorised units under Guderian, Rommel and others, advanced far beyond the marching and horse-drawn infantry divisions and far in excess of that with which Hitler and the German high command expected or wished. When the Allies counter-attacked at Arras using the heavily armoured British Matilda I and Matilda II tanks, a brief panic was created in the German High Command. The armoured and motorised forces were halted by Hitler outside the port of Dunkirk, which was being used to evacuate the Allied forces. Hermann Göring promised that the Luftwaffe would complete the destruction of the encircled armies but aerial operations failed to prevent the evacuation of the majority of the Allied troops. In Operation Dynamo some 330,000 French and British troops escaped.[87]
Germany invaded the Soviet Union in June 1941.[236] German propaganda portrayed the war against the Soviet Union as both an ideological war between German National Socialism and Jewish Bolshevism and a racial war between the Germans and the Jewish, Romani and Slavic Untermenschen ("sub-humans").[237] Local populations in some occupied Soviet territories actively participated in the killing of Jews and others, and helped identify and round up Jews.[238] German involvement ranged from active instigation and involvement to general guidance.[239] In Lithuania, Latvia, and western Ukraine, locals were deeply involved in the murder of Jews from the beginning of the German occupation. Some of these Latvian and Lithuanian units also participated in the murder of Jews in Belarus. In the south, Ukrainians killed about 24,000 Jews and some went to Poland to serve as concentration and death-camp guards.[238] Military units from some countries allied to Germany also killed Jews. Romanian units were given orders to exterminate and wipe out Jews in areas they controlled.[240] Ustaše militia in Croatia persecuted and murdered Jews, among others.[168] Many of the killings were carried out in public, a change from previous practice.[241]
Schindler grew up in Svitavy, Moravia, and worked in several trades until he joined the Abwehr, the military intelligence service of Nazi Germany, in 1936. He joined the Nazi Party in 1939. Prior to the German occupation of Czechoslovakia in 1938, he collected information on railways and troop movements for the German government. He was arrested for espionage by the Czechoslovak government but was released under the terms of the Munich Agreement in 1938. Schindler continued to collect information for the Nazis, working in Poland in 1939 before the invasion of Poland at the start of World War II. In 1939, Schindler acquired an enamelware factory in Kraków, Poland, which employed at the factory's peak in 1944 about 1,750 workers, of whom 1,000 were Jews. His Abwehr connections helped Schindler protect his Jewish workers from deportation and death in the Nazi concentration camps. As time went on, Schindler had to give Nazi officials ever larger bribes and gifts of luxury items obtainable only on the black market to keep his workers safe.