text:
Conflict of Interest:A. Blumenfeld: Research grants from Allergan, Inc., GlaxoSmithKline, Medtronic, Inc., and Pfizer, Inc., and consultancy with Allergan, Inc., GlaxoSmithKline, Medtronic, Inc., Merck, Ortho-McNeill, Pfizer, Inc.; S.D. Silberstein: Research grants from Advanced NeuroModulation Systems, AGA, Allergan, Inc., Boston Scientific, Coherex, Endo, GlaxoSmithKline, Lilly, MAP, Medtronic, Inc., Merck, NuPathe, and Valeant, and consultancy with Allergan, Inc., AGA, Capnia, Coherex, Endo, GlaxoSmithKline, MAP, Medtronic, Inc., Merck, NuPathe, and Valeant; D.W. Dodick: Honoraria for consulting with Allergan, Inc., Addex, Alexza, Coherex, Eli Lilly, Endo, GlaxoSmithKline, H. Lundbeck A/S, Kowa, MAP, Medtronic, Merck, Minster, Neuralieve, Neuraxon, Novartis, NuPathe, Pfizer, Inc., and research grants (to institution) on behalf of investigator from ANS, Medtronic, Inc., and St. Jude; S.K. Aurora: Research grants from Alexza, Allergan, Inc., AstraZeneca, GlaxoSmithKline, Merck, and Winston, and honoraria for consulting with Allergan, Inc., Astra Zeneca, GlaxoSmithKline, Merck, Ortho-McNeil, NMT, Pfizer, Inc., and Valeant; C.C. Turkel: Employee and shareholder of Allergan, Inc.; W.J. Binder: Consultant and shareholder of Allergan, Inc.
Method of Injection of OnabotulinumtoxinA for Chronic Migraine: A Safe, Well-Tolerated, and Effective Treatment Paradigm Based on the PREEMPT Clinical Program
Version of Record online: 4 OCT 2010
DOI: 10.1111/j.1526-4610.2010.01766.x
© 2010 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 50, Issue 9, pages 1406–1418, October 2010
Additional Information
How to Cite
Blumenfeld, A., Silberstein, S. D., Dodick, D. W., Aurora, S. K., Turkel, C. C. and Binder, W. J. (2010), Method of Injection of OnabotulinumtoxinA for Chronic Migraine: A Safe, Well-Tolerated, and Effective Treatment Paradigm Based on the PREEMPT Clinical Program. Headache: The Journal of Head and Face Pain, 50: 1406–1418. doi: 10.1111/j.1526-4610.2010.01766.x
Publication History
- Issue online: 4 OCT 2010
- Version of Record online: 4 OCT 2010
- Accepted for publication August 3, 2010.
- Abstract
- Article
- References
- Cited By
- chronic migraine;
- onabotulinumtoxinA;
- prophylaxis;
- prevention
- Top of page
- Abstract
Chronic migraine (CM) is a prevalent and disabling neurological disorder. Few prophylactic treatments for CM have been investigated. OnabotulinumtoxinA, which inhibits the release of nociceptive mediators, such as glutamate, substance P, and calcitonin gene-related peptide, has been evaluated in randomized, placebo-controlled studies for the preventive treatment of a variety of headache disorders, including CM. These studies have yielded insight into appropriate patient selection, injection sites, dosages, and technique. Initial approaches used a set of fixed sites for the pericranial injections. However, the treatment approach evolved to include other sites that corresponded to the location of pain and tenderness in the individual patient in addition to the fixed sites. The Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) injection paradigm uses both fixed and follow-the-pain sites, with additional specific follow-the-pain sites considered depending on individual symptoms. The PREEMPT paradigm for injecting onabotulinumtoxinA has been shown to be safe, well-tolerated, and effective in well-designed, controlled clinical trials and is the evidence-based approach recommended to optimize clinical outcomes for patients with CM.
chronic daily headache
chronic migraine
fixed-site, fixed-dose
Phase III REsearch Evaluating Migraine Prophylaxis Therapy
Chronic migraine (CM) is a disabling neurologic disorder that affects 1.4-2.2% of the general population.1,2 Patients with CM experience headache ≥15 days per month for ≥3 months, with headaches occurring on ≥8 days being classified as migraine headaches or headaches that respond to migraine-specific medications.3 CM is the most common type of primary chronic daily headache (CDH) seen in headache specialty centers in the USA.i,3-5
The overuse of acute headache medications can be a problem for patients with chronic headache disorders. Most CM patients who seek treatment in tertiary headache clinics overuse acute headache medications.6 An effective, safe, and well-tolerated prophylactic headache medication will improve the patient's clinical condition and should reduce acute headache medication consumption.1,7 Only 33.3% of CM patients use prophylactic headache medication.1
OnabotulinumtoxinA has been reported to relieve pain in a variety of conditions, including migraine.8-20 Efficacy results from previous trials in patients with episodic migraine (generally understood as occurring <15 days per month) have been negative.10,21-23 Results from exploratory trials in episodic migraine, chronic tension-type headache, and CDH have been mixed, but have suggested that onabotulinumtoxinA may be useful as preventive treatment for CDH, specifically patients suffering from CM.8-10,24-26 Various onabotulinumtoxinA dosages and injection paradigms have been evaluated in these studies,8-10,24-26 and the Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) injection protocol evolved from these paradigms. Pivotal results from the PREEMPT clinical program have established onabotulinumtoxinA as a safe, well-tolerated, and effective headache prophylactic treatment for CM.27-29
Although the exact mechanism of onabotulinumtoxinA in antinociception has not been fully elucidated, animal and human studies indicate that onabotulinumtoxinA inhibits the release of nociceptive mediators, such as glutamate, substance P, and calcitonin gene-related peptide, from peripheral termini of primary afferents (nociceptors).30-37 Blocking release of these neurotransmitters inhibits neurogenic inflammation; this, in turn, inhibits peripheral sensitization of nociceptive (pain-conducting) nerve fibers. As a result, peripheral pain signals to the central nervous system are reduced and, indirectly, central sensitization is blocked.30,31,36,37
The goal of this review is to provide an evidence-based clinical approach for treating CM with onabotulinumtoxinA. This review discusses patient selection, dosing, injection site selection, and injection techniques.
- Top of page
- Abstract
Localized pericranial injections of onabotulinumtoxinA were first reported to alleviate migraine symptoms in patients with episodic migraine who had received treatment for hyperfunctional facial lines in a multicenter, open-label study. The study found that 89% of patients with episodic migraine who were treated with onabotulinumtoxinA had complete or partial response of their migraine symptoms, including headache.38 Other, placebo-controlled, exploratory studies of episodic migraine patients (history of ≥3 moderate to severe migraines and ≤15 headache days per month) did not demonstrate statistically superior improvement in patients treated with onabotulinumtoxinA.21-23,25 However, these trials did help to identify a patient population potentially responsive to onabotulinumtoxinA treatment. In one study, a post-hoc subgroup analysis of patients with the highest baseline frequencies of headache days (ie, ≥12 and ≤15 per month) found that onabotulinumtoxinA-treated patients experienced a significant mean decrease from baseline in headache episodes at Day 180 (the primary time-point) compared with placebo-treated patients (P = .048).25 These results suggest that patients suffering very frequent headache attacks may be the ones most likely to benefit from prophylactic onabotulinumtoxinA treatment.
Results of 2 additional exploratory, well-designed, randomized, double-blind, placebo-controlled trials have provided further insight into which patients, dosages, and injection protocol may yield the best results from prophylactic onabotulinumtoxinA therapy.8,24 Together, these trials recruited >1000 patients with CDH (>15 headache days per month) who could have had any combination of migraine and/or episodic or chronic tension-type headache. Baseline data from these studies indicated that the majority of patients enrolled likely suffered from CM.8,24,39 Each study used a different approach (fixed-site or follow-the-pain [FTP], discussed below) and different doses of onabotulinumtoxinA (75-260 U). The primary outcome measures of these exploratory trials were not met, although improvements from baseline for the treatment groups were reported in both trials.8,24 In one trial, several secondary measures showed statistically significant benefit with onabotulinumtoxinA treatment vs placebo treatment,8 which suggested that further analysis was warranted to identify a specific subgroup of patients.39 A subgroup analysis that excluded patients taking other headache prophylactic treatments showed a statistically significant improvement in the frequency of headache-free days at 6 months, the primary end-point (10.0 days in the onabotulinumtoxinA group vs 6.7 days in the placebo group, P = .038). A significant reduction at 6 months in the mean frequency of headaches per 30 days that favored onabotulinumtoxinA treatment was also observed (−7.8 in the onabotulinumtoxinA group vs −4.5 in the placebo group; P = .032).39 This subgroup analysis was conducted also based on recommendations from migraine controlled-trial guidelines that recommend monotherapy studies because concomitant treatment may confound study results.40-42 Overall, these exploratory phase 2 studies provided guidance and shaped the study design and the injection paradigm of the phase 3 PREEMPT clinical program.
Another controlled study demonstrated the effectiveness of 100 U onabotulinumtoxinA in the treatment of patients with CM who specifically did not overuse pain medication. In this study, which used a fixed-site administration approach, patients in the onabotulinumtoxinA treatment group had a statistically significant and clinically meaningful (31.0%) decrease in migraine frequency (primary end-point) compared with the 8.9% decline for those in the placebo-treated group (P < .001).9
More recently, the PREEMPT clinical program has confirmed onabotulinumtoxinA as an effective, safe, and well-tolerated prophylactic treatment for adults with CM.27 These two phase 3, multicenter studies (PREEMPT 1 & 2), each of which had a 24-week, double-blind, parallel-group, placebo-controlled phase followed by a 32-week open-label phase, enrolled 1384 patients with CM. In these studies, all patients received a minimum intramuscular (IM) dose of 155 U of onabotulinumtoxinA administered to 31 injection sites across 7 head and neck muscles using a fixed-site, fixed-dose (FSFD) injection paradigm (each injection was 5 U in 0.1 mL). In addition, up to 40 U onabotulinumtoxinA, administered IM to 8 additional injection sites across 3 head and neck muscles, was allowed, using a FTP approach. Thus, the minimum dose was 155 U and the maximum dose was 195 U.27
Important end-points (primary and secondary) were change from 28-day baseline compared with the 28 days ending at Week 24 for frequency of headache days (primary PREEMPT 2; secondary PREEMPT 1) and headache episodes (primary PREEMPT 1; secondary PREEMPT 2). Statistically significant reductions from baseline for frequency of headache days after onabotulinumtoxinA treatment compared with placebo treatment in both PREEMPT 1 (P = .006) and PREEMPT 2 (P < .001) were observed.28,29 Statistically significant improvement from baseline after onabotulinumtoxinA compared with placebo treatment was seen for headache episodes in PREEMPT 2 (P = .003),29 but not in PREEMPT 1.28 Pooled analysis demonstrated that onabotulinumtoxinA treatment significantly reduced mean frequency of headache days (−8.4 onabotulinumtoxinA, −6.6 placebo; P < .001) and headache episodes (−5.2 onabotulinumtoxinA, −4.9 placebo; P = .009).27 Several other efficacy variables (migraine episodes, migraine days, moderate or severe headache days, cumulative hours of headache on headache days, and proportion of patients with severe disability) showed significant between-group differences favoring onabotulinumtoxinA. The PREEMPT results showed highly significant improvements in multiple headache symptom measures and demonstrated improvement in patients' functioning, vitality, psychological distress, and overall quality of life.27
A literature review of the randomized, double-blind, placebo-controlled clinical studies of onabotulinumtoxinA as headache prophylaxis treatment for CM reports adverse events (AEs) that were consistent with the known safety and tolerability profile of IM administration of onabotulinumtoxinA. The safety profile indicates that onabotulinumtoxinA is safe and well-tolerated in the CM population, with few patients discontinuing treatment due to AEs (1.4-3.8%).8,24,27-29,43 In contrast, other prophylactic headache treatments report discontinuation rates due to AEs as high as 12.7%.43 Several epidemiologic surveys indicate that preventive therapies are significantly underutilized; only a minority of patients who could benefit from preventive therapy are currently treated (6-13% in population-based surveys).7,44,45 Thus, a substantial proportion of migraine sufferers who might benefit from prevention do not receive it. A study of patient adherence to prophylactic migraine medication showed that 35% of enrolled patients were nonadherent.46 Another study revealed that approximately 75% of the study population (n = 729) had stopped or switched prophylactic treatment for migraine after 1 year.47 Given the substantial AEs and adherence issues associated with available pharmacotherapies for CM, the relatively mild AEs associated with onabotulinumtoxinA treatment may present an attractive treatment alternative.
- Top of page
- Abstract
Patient Selection.— Identifying headache disorder(s) that respond to onabotulinumtoxinA treatment has been the subject of clinical exploration for more than a decade. Initial research evaluated patients with various headache disorders, such as cervical-associated headache,48 episodic migraine,10,38 CM,8,9,24 and chronic tension-type headache.26,49 PREEMPT results support previous studies,8,24,39 which identified CM patients as the ones most likely to benefit from onabotulinumtoxinA treatment. Results from the onabotulinumtoxinA pivotal studies confirm that patients with CM, including those who were overusing acute headache medication during the 28-day baseline period, benefit from this treatment.27-29
Dose.— Between 1997 and 2000, 5 exploratory, randomized, double-blind, placebo-controlled, parallel-group design studies of episodic migraine were conducted. In these studies, each treatment arm used a FSFD IM injection paradigm with the intent of determining which muscle(s) and dose(s) were effective. Doses ranged from 6 to 75 U, and the number of injection sites ranged from 3 to 11, administered IM in up to 4 muscle groups, all in the front of the head (ie, corrugator, procerus, frontalis, and temporalis) with no posterior head or neck injections.10,21,22 Two of these studies evaluated a single treatment cycle and patients were followed for approximately 16 weeks.10,21 The other 3 studies evaluated multiple treatment cycles repeated at 120-day intervals in sequential follow-on studies.22
In 2001, 4 additional larger, exploratory, randomized, double-blind, placebo-controlled, parallel-group design studies were initiated: 2 in patients with episodic migraine and 2 in patients with CDH. All 4 studies utilized a FSFD treatment paradigm. In 2 of the studies, additional treatments were allowed in predefined head and neck muscles where patients had predominant pain. Doses evaluated in these studies ranged from 75 U in 20 injection sites across 7 specific head and neck muscles23,24 to 260 U in 58 injection sites across 7 specific head and neck muscles.8,25 In one of these phase 2 studies in CDH,24 the dose included 225 U, 150 U, and 75 U groups and provided insight with regard to the optimally safe and effective dosage per injection cycle. However, in this trial a dose–response was observed for tolerability, with the 225 U dose group having more AEs (eg, muscle weakness, neck pain) than the other 2 treatment groups. With regard to efficacy, the 2 higher dose groups were both different from the 75 U group, but there was no difference in efficacy between the 225 U and 150 U groups. Therefore, it was determined that the optimal total dose to maximize efficacy and tolerability was within the range of >150 U and <200 U. PREEMPT confirmed that 155-195 U of onabotulinumtoxinA is efficacious for treating patients with CM.27-29
Injection Sites and Techniques.— Dilution volume used for each 100 U vial of onabotulinumtoxinA varied across the early studies, which could have also contributed to varied findings across these studies, and this is another important factor to consider for this injectable treatment. Early exploratory studies diluted each vial with 1.33-10 mL, which resulted in onabotulinumtoxinA concentrations that ranged from 7.5 U/0.1 mL to 0.1 U/0.1 mL.10,21,22 The occurrence of eyelid ptosis, which may be influenced by the dose and dilution administered to the frontal muscles (corrugator, procerus, and frontalis muscles), was seen in up to 17.5% patients10 injected with a total maximum dose of 57 U (75 U group) (dilution 1.33 mL/vial) to these muscles. In another study, despite a maximum dose of only 19 U in these muscles (25 U total dose group), ptosis was reported at a rate of 14.3% when using a dilution of 4 mL/vial.21 In the double-blind, placebo-controlled phase of the pivotal phase 3 PREEMPT trials, ptosis was reported at low rates (3.6% of onabotulinumtoxinA-treated and 0.3% of placebo-treated patients)27 with a total dose of 35 U to the frontalis, corrugator, and procerus muscles. In PREEMPT, each 100 U vial of onabotulinumtoxinA was diluted with 2 mL preservative-free normal saline, resulting in a concentration of 5 U/0.1 mL.
To ensure the stability of the protein, the package insert for onabotulinumtoxinA (BOTOX®) recommends reconstitution with preservative-free normal saline (0.9% Sodium Chloride, USP).50 Once a 100 U vial of onabotulinumtoxinA has been reconstituted, it must be injected or immediately stored in a refrigerator at 2-8°C in the original vial (not in a syringe) and used within 24 hours50 or as indicated in the local package insert.
In the development of a treatment paradigm for onabotulinumtoxinA injections, perhaps the greatest evolution has been in the selection of sites for the injections. As mentioned above, 2 approaches have been widely used: fixed-site/fixed-dose and follow-the-pain. It was previously believed that the type of approach depended on the type of headache, but whether one approach should be preferred over the other has not previously been firmly established. Early headache studies generally used a fixed-site approach, identifying sites in the forehead and glabellar region while generally avoiding the occipital and neck regions.10,51 The fixed-site approach distributes onabotulinumtoxinA to muscles that align with the peripheral nerve distribution of the cervical and trigeminal sensory system, which is believed to be the target-end organ for onabotulinumtoxinA in treating CM. These sites remain unchanged regardless of where the patient's pain is located. The PREEMPT injection paradigm, which uses a combination of fixed and FTP injection sites, provides optimal distribution of onabotulinumtoxinA based on individual patient symptoms.8,24
The muscle groups chosen in PREEMPT were based on in-depth analysis of the interaction effects of muscle group dose on efficacy variables in patients who were not using prophylactic headache medication during baseline, and in-depth analyses of the safety and tolerability of the dose and dosage paradigm used in the 2 Allergan-sponsored phase 2 studies of patients with CDH.8,24 The findings from these analyses, which are discussed further below, serve as the foundation for the choice of muscles, dose, and dilution used in the PREEMPT studies.
Frontalis, Corrugator, and Procerus (Frontal/Glabellar Region).— In the phase 2 trials,8,24 patients reported that the frontal/glabellar region was the most frequent location where their head pain started and ended. In the first trial, doses for the frontal/glabellar region were not specified; only a total dose was specified for the overall region, which was administered across the frontalis, corrugator, and procerus muscles. In the second trial, the frontalis and corrugator muscles of the forehead were injected, but not the procerus muscle. Overall, the first trial had better signals for efficacy than the second trial. Thus, to ensure the best chance for efficacy as well as ensure consistency and standardization of treatment, the PREEMPT paradigm used the muscles that were injected in the first trial: the frontalis, corrugator, and procerus.
The AE rate of eyelid ptosis was 7.5% in the onabotulinumtoxinA-treated group in the first trial,8 and 4.8% and 6.6% in the 150 U and 225 U dose groups, respectively, in the second trial.24 To reduce the potential for focal AEs such as eyelid ptosis, a slightly lower total dose (35 U) than the average dose administered to the frontal muscles in the second trial (40 U) was chosen for evaluation in the phase 3 PREEMPT studies. Furthermore, in the PREEMPT trials the exact number of injections and location for injection to these muscles was specified in the protocol and injection training to ensure optimal tolerability and to specifically reduce the eyelid ptosis AE rates observed in the phase 2 trials. Indeed, the PREEMPT injection method in these muscles appears to have achieved these goals, because the PREEMPT clinical program had statistically significant separation from placebo across multiple headache symptom measures, with an overall eyelid ptosis rate of 3.6% for onabotulinumtoxinA-treated patients in the double-blind, placebo-controlled phase of the pooled phase 3 trials.
Temporalis.— In the phase 2 trials,8,24 patients reported that the temporalis area was the second most frequent location where their head pain started and ended. The FSFD for this muscle in the phase 3 trials was determined based on the fact that the mean dose administered to the temporalis muscle in the first trial was ∼40 U (∼20 U per side) and the maximum dose was 50 U. There were no emerging tolerability issues from injecting this muscle at these doses in the phase 2 trials. Because this muscle was a very common location of predominant pain for many patients in the phase 2 trials, it was decided that for the PREEMPT paradigm the total dose of 40 U (20 U per side) would be required as a minimum dose, and an allowance for an additional 10 U to this muscle area could be given using the FTP regimen.
Cervical Paraspinal Muscle Group (Neck Muscles).— In the phase 2 trials,8,24 patients indicated that their headache pain frequently started and/or stopped in the back of the head (either in the occipitalis and/or the neck). The splenius capitis and semispinalis muscles were the neck muscles injected in both phase 2 trials. The protocols allowed investigators some discretion as to specific injection location in these muscles, and many of the investigators administered the treatment to the mid-neck region and often injected these muscles using longer needles to ensure that they reached the semispinalis muscle. In the second trial, which was a dose-ranging, FSFD regimen trial, patients in the middle- and high-dose groups showed a relatively high incidence of neck pain (∼25%). In some instances, neck muscle weakness resulted in patients needing temporary soft collars to support their head. In this trial, patients in the middle- and high-dose groups received 20 U and 30 U, respectively, to each side of the splenius capitis and semispinalis neck muscles, for total doses of 40 U and 60 U, respectively, across these 2 muscle groups. The incidence of neck pain (13.3%) in patients treated in first trial (which had variable neck dose that could range from 20 to 40 U total across the semispinalis and splenius capitis muscles) was not as high; these patients received average doses of ∼18 U in each muscle group for a total mean dose in the mid-neck region of ∼36 U.
Upon review of the tolerability data, the PREEMPT injection paradigm for the neck was revised. Injections were to be given to the upper neck (cervical paraspinal muscles) at the base of the skull, rather than to the mid-neck region. The FTP injection regimen was not allowed in the neck region, and injections were to be more superficial rather than deep into the neck muscles. Hence, the injection needle length and gauge were standardized to 0.5 inch and 30 gauge, respectively, which is shorter and a smaller bevel than what had been allowed in the second phase 2 trial (that trial had allowed use of up to 1.5 inch and/or larger 27-gauge needle). Furthermore, it was decided to reduce the total dose injected into the neck region. The overall dose was reduced to a FSFD of 20 U for this muscle group (10 U to each side of the head). It was anticipated that this dose would be sufficient from an efficacy perspective and that the lower neck dose would result in less neck pain and neck rigidity, and also decrease the risk of excessive neck muscle weakness, which would improve the overall tolerability profile while maintaining efficacy. The overall AE rates in the pooled analysis of the double-blind, placebo-controlled phase of the PREEMPT studies was less than what was observed in the phase 2 studies, with neck pain occurring in 8.7% of the onabotulinumtoxinA-treated patients vs 2.7% of the placebo-treated patients.27 There was only 1 patient in PREEMPT who required a soft collar due to excessive weakness, compared with 10 patients in the phase 2 studies, confirming that a reduction in the dose and needle length was appropriate.
Occipitalis.— In the phase 2 trials,8,24 patients reported that occipitalis was the third most frequent location where their head pain started and ended. The phase 2 data were also evaluated to ascertain the frequency of FTP paradigm actually used by clinicians in the first trial, because variation in the dosage was allowed for all muscle groups in that protocol except for the occipitalis. The mean and median doses for each muscle group showed that the dosages for the temporalis and trapezius muscles were the muscle groups with the most variation across patients, which indicated FTP was most frequently used for these muscle groups. Most patients have predominant pain on one side of the head, or in the back of the head, or in the shoulders that may warrant additional treatment to those areas. Because a decision had been made to reduce the overall dose administered to the neck and to not allow FTP regimen in the neck muscles (as described above), there was concern that there would be insufficient "back of the head" dose to ensure efficacy, especially since so many patients complain of pain in that area. Thus, the minimum dose administered to the occipitalis was increased from the phase 2 dose, and, to reduce risk of neck weakness, the sites for injection into the occipitalis were located primarily above the occipital ridge, which would also reduce the risk of neck weakness. Furthermore, if patients had a complaint of predominant pain in the back of the head, additional FTP dosing would be allowed in this muscle.
Trapezius.— In the phase 2 trials,8,24 approximately 20-30% of patients reported that their headache pain started and/or ended in the trapezius muscles. In the second trial, the total doses administered to the trapezius muscles were 20 U, 40 U, and 60 U in the 75 U, 150 U, and 225 U dose groups, respectively. The incidence of arm (shoulder) pain, which was felt to be related to injections into the trapezius muscle due to the close location and the thinness of the muscle at the proximal location near the shoulder muscle, was higher for the 2 higher dose groups: 8.2% in the 225 U group and 8.9% in the 150 U group compared with 6.3% in the 75 U group. In the first trial, the mean dose administered to the trapezius was ∼48 U and the incidence of arm (shoulder) pain was 5.8%, which is lower than that observed in the second trial. The incidence of arm (shoulder) pain in the patients who received the maximum 60 U dose was not felt to be a general safety concern, but at the same time there was a desire to minimize patient discomfort while ensuring optimum efficacy from this treatment. Thus, the dosage regimen for the trapezius muscle in the PREEMPT clinical program was standardized to a minimum dose of 30 U (15 U on each side), with the option for additional FTP treatment to a maximum dose of 50 U (up to 20 U additional administered as 5 U per injection site divided across 1 or both sides) if clinically needed. This standardization was appropriate, as demonstrated by the reduction in the incidence of arm (shoulder) pain for onabotulinumtoxinA-treated patients (2.9%) in the double-blind phase of PREEMPT.
Masseter Muscle.— The masseter muscle, which was an optional muscle that could have been injected in the first phase 2 trial,8 was not included as a muscle to be injected in PREEMPT. The masseter muscle was injected in only 24% (84/355) of patients in that trial, and clinical data analyses suggested that patients who received masseter injections did not benefit from onabotulinumtoxinA treatment to the same extent as those who did not receive masseter injections. It was unclear from this finding whether patients who were manifesting pain in the masseter region represent a subgroup of chronic migraineurs and/or whether comorbid chronic pain conditions of temporomandibular disorder or chronic pain in or around the temporomandibular joint were potentially confounding the results. Although there was no indication of specific AEs resulting from masseter injection, neither was there evidence that including the masseter muscle enhanced the efficacy; hence, it was not included as a target muscle group for injection in the phase 3 PREEMPT trials.
- Top of page
- Abstract
Based on exploratory phase 2 CM studies detailed above,8,24 the PREEMPT clinical program evaluated a standardized treatment paradigm.27-29 Using this standardized paradigm, a minimum dose of 155 U of onabotulinumtoxinA was administered as 31 FSFD injections across 7 specific head/neck muscles (Table). Up to 40 U of additional onabotulinumtoxinA could have been administered at the physician's discretion using a FTP strategy into the temporalis, occipitalis, and/or trapezius muscles, with a maximum dose of 195 U administered to 39 sites (Table). When deciding on dose and location of additional onabotulinumtoxinA, physicians took into consideration the location of the patient's predominant pain and the severity of palpable muscle tenderness.
|Head/Neck Area
|Recommended Dose:
|Total dosage (number of sites†)
|20 units (in 4 sites)
|10 units (in 2 sites)
|5 units (in 1 site)
|30 units (in 6 sites), rebreak up to 40 units in 8 sites
|40 units (in 8 sites), rebreak up to 50 units in 10 sites
|30 units (in 6 sites), rebreak up to 50 units in 10 sites
|Cervical paraspinal muscle group‡
|20 units (in 4 sites)
|Total dose range
|155 units to 195 units
The PREEMPT injection paradigm involved a minimum of 31 injections to 7 specific head and neck muscle areas. Patients were placed supine for injections into the corrugator, procerus, frontalis, and temporalis, and these muscles were injected first, in that order. Patients were sitting for injections into the occipitalis, cervical paraspinal, and trapezius muscles. The physician palpated each muscle (bilaterally, if appropriate) prior to injection to verify muscle delineation, and determined whether there was any muscle tenderness and areas of pain that required additional treatment. The PREEMPT injection paradigm dose for CM was 155-195 U administered IM using a sterile 30-gauge, 0.5-inch needle as 0.1 mL (5 U) injections per each site. A 1-inch needle was allowed in the neck region for patients with thick neck muscles. The treatment paradigm recommended wearing gloves while the treatment was administered. Prior to injection, the skin was cleansed according to standard practice for IM injections (eg, with alcohol). The needle was inserted into the muscle with the bevel up, at approximately a 45-degree angle. Once the needle was inserted into the muscle, the hub of the needle was held with one hand to ensure that the needle did not torque in the skin. The plunger was pulled back slightly with the other hand to ensure no blood return, and the plunger was then pushed to administer 0.1 mL (5 U) to each designated injection site. If bleeding or bruising occurred, gentle pressure was applied. Injections were not given intravenously.
Corrugator and Procerus.— Injections started in the glabellar region, which consists of the corrugator and procerus muscles. These muscles are shallow, so the needle was kept superficial to avoid hitting the periosteum. A total of 2 FSFD injections were given to the corrugator muscle, one on each side of the forehead. According to the paradigm, the injection site is located approximately 1.5 cm (1 finger's breadth) above the medial superior edge of the orbital ridge (bony landmark). The thumb was placed under the corrugator muscle and the injection was done with the needle angled up and away from the eye (toward the forehead), to prevent ptosis of the eyelid (Fig. 1A). Ptosis occurs when toxin diffuses into the medial portion of the upper eyelid where the levator palpebrae superioris muscle is located.52
According to the paradigm, the procerus muscle has 1 FSFD injection site, in the midline of the forehead approximately 1.5 cm above the medial superior aspect of the orbital ridge (bony landmark) of each eye. This injection site is midway between the 2 corrugator injections (Fig. 1B), as if there is a single horizontal line connecting all 3 of these injections.
Frontalis.— Each physician then injected the frontalis muscle, which is shallow, so the needle was kept superficial to avoid hitting the periosteum. Each injection diffuses over an area about 2 cm in diameter once the needle pierces the skin (Fig. 1C), thus the needle did not need to be directed upward for these injections. According to this paradigm, there are a total of 4 FSFD frontalis injections (2 on the left side and 2 on the right). For medial injection sites, a visual line was drawn up from the medial edge of the eyebrow about 1.5 cm (1 finger's breadth) from the corrugator injection site. The lateral injection sites are parallel and approximately 1.5 cm lateral of the medial injections sites.
Temporalis.— The temporal area received a total of 8 FSFD injections, 4 to each side. Up to 2 additional injections using the optional FTP paradigm were allowed. Prior to any injection, the muscles on both sides of the head were palpated for tenderness or pain. Each physician started with the 4 fixed-site injections on the left side of the head as indicated in Figure 1D. The patient was instructed to clench his or her teeth to assist in the location of the anterior aspect of the temporalis muscle, which was palpated. The first injection was made just behind this point (approximately 2 fingers' breadth) behind the hairline. The second injection was made approximately 0.5 cm superior and 1.5 cm posterior to the first injection in the medial aspect of the muscle. The third injection site was found parallel and approximately 1.5 cm posterior to the second injection. The fourth fixed-site injection was 1.5 cm below and perpendicular to the second injection, into the medial aspect of the muscle (Fig. 1D). If a decision was made to inject additional onabotulinumtoxinA into the temporalis muscle, it was injected in this side before the right side of the head (Fig. 2D). The PREEMPT injection paradigm recommends that an additional injection site be used rather than increasing the volume for any given prior injection site.
Occipitalis.— Prior to injecting the occipital area, both the left and right sides were palpated to identify the areas of tenderness and/or pain. The external occipital protuberance was palpated to locate the occipitalis injection sites, which are superior to the supranuchal ridge on either side of this protuberance (Fig. 1E). Three injections were administered to the right and left occipitalis muscles, for a total of 6 FSFD injections (Fig. 1E). The first injection was given just above the occipital protuberance along the supranuchal ridge and approximately 1 cm left/right (depending on the side) of the external occipital protuberance. The second injection was given approximately 1 cm to the left/right and approximately 1 cm above the first injection. The third injection was given 1 cm medial and 1 cm above the first injection site. According to the FTP optional dosing paradigm, an additional 2 injections could have been distributed between the right and left occipitalis muscles (1 injection on each side or 2 injections on 1 side) in the areas identified as having maximal tenderness (Fig. 2E).
Cervical Paraspinal Muscle Group.— Beginning on the left side, the cervical paraspinal muscle group injection sites were located by palpating the cervical spine (Fig. 1F). It was important not to go too deep into the cervical paraspinal and trapezius muscles with the injections, and the hub of the 0.5-inch needle served as a relatively accurate "depth" guide. The first injection was administered lateral to the midline, approximately 3-5 cm inferior to the occipital protuberance. A second injection was administered on the same side, 1 cm lateral and superior to the first injection (diagonally toward the ear from the first injection). This procedure was repeated symmetrically on the contralateral side, for a total of 4 FSFD injections.
Trapezius.— Lastly, the superior portions of the trapezius muscles were palpated to identify areas of tenderness and/or pain. Beginning on the left side, the muscle was visually divided into 3 sections (Fig. 1G). The first injection was administered in the lateral aspect of the muscle. The physician then moved medially, to the mid-portion of the trapezius, and administered the second injection. The third injection was administered medially and superiorly within the third section of the muscle. This procedure was repeated symmetrically on the contralateral side for a total of 6 FSFD injections. According to the FTP optional dosing paradigm, an additional 4 injections could have been distributed between the right and left trapezius muscles in the areas identified as having maximal tenderness (Fig. 2G). Physicians exercised caution when deciding to inject additional units of onabotulinumtoxinA into the trapezius muscles, and avoided the infero-medial portions of the trapezius muscle (Fig. 2G; see arrow) to limit the possibility of neck weakness.
Patients were observed for 10-15 minutes following treatment. Patients were advised not to rub or massage the affected areas for 24 hours, and told that any bumps that appeared on the forehead should disappear within approximately 2 hours. Patients were advised that they may need, and should use, their acute medications for breakthrough headaches. Retreatment occurred at 12-week intervals. In the interim, patients were encouraged to maintain a headache diary.
- Top of page
- Abstract
OnabotulinumtoxinA has been found to be effective, safe, and well-tolerated for the prophylaxis of headache in adults with CM at doses ranging from 155 to 195 U administered IM across 7 head and neck muscles every 12 weeks for up to 5 treatment cycles.27-29 Discontinuation rates due to AEs were low, and most AEs reported were transient, mild to moderate in severity, and localized to the sites of injection. This tolerability profile may make onabotulinumtoxinA more appealing than systemic agents for long-term treatment as headache prophylaxis in adults with CM.
Previous studies evaluating onabotulinumtoxinA for a range of primary headache disorders employed a variety of dose ranges and injection site approaches; PREEMPT built upon those trials and established an effective injection paradigm that confirmed the efficacy, safety, and tolerability of onabotulinumtoxinA for the prophylactic treatment of headaches in adults with CM. The PREEMPT injection paradigm targets a broad distribution of V1 and C2 dermatomes and is the optimal injection strategy of onabotulinumtoxinA for patients with CM. Because onabotulinumtoxinA may be part of a comprehensive treatment program, it is recommended that injections of onabotulinumtoxinA for the prophylactic treatment of CM be utilized only by those healthcare providers who have experience in the comprehensive management of this complex patient population as well as experience in the use of onabotulinumtoxinA.
- Top of page
- Abstract
Dosing and treatment paradigm are specific to the formulation of onabotulinumtoxinA manufactured by Allergan, Inc. (Irvine, CA, USA), which, as noted on US Food and Drug Administration labeling, is not interchangeable with other preparations of botulinum toxin products. As of August 31, 2010, onabotulinumtoxinA has received regulatory approval for the treatment of chronic migraine in the United Kingdom and Estonia.
Acknowledgments: The authors would like to thank Allergan, Inc., for funding IntraMed Educational Group, New York, NY, to provide editorial support in the preparation and styling of this manuscript.
- Top of page
- Abstract
- 1Chronic migraine in the population: Burden, diagnosis, and satisfaction with treatment. Neurology. 2008;71:559-566., , , .
- 2Global prevalence of chronic migraine: A systematic review. Cephalalgia. 2010;30:599-609., , , et al.
- 3New appendix criteria open for a broader concept of chronic migraine. Cephalalgia. 2006;26:742-746., , , et al.
- 4Chronic daily headache. Curr Opin Neurol. 2000;13:277-283., .
- 5
- 6Transformed migraine and medication overuse in a tertiary headache centre – clinical characteristics and treatment outcomes. Cephalalgia. 2004;24:483-490., , , , .
- 7Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343-349., , , , , .
- 8Botulinum toxin type A (BOTOX®) for the prophylactic treatment of chronic daily headache: A randomized, double-blind, placebo-controlled trial. Headache. 2005;45:293-307., , , , , .
- 9Botulinum toxin type A in the treatment of chronic migraine without medication overuse. Headache. 2008;48:201-209., , , .
- 10Botulinum toxin type A as a migraine preventive treatment. For the BOTOX® Migraine Clinical Research Group. Headache. 2000;40:445-450., , , .
- 11Clinical comparisons of botulinum neurotoxin formulations. Neurologist. 2008;14:289-298..
- 12Safety and efficacy of botulinum toxin type A following long-term use. Eur J Neurol. 2006;13(Suppl 4):35-40., , , , .
- 13Botulinum neurotoxins in the treatment of refractory pain. Nat Clin Pract Neurol. 2008;4:676-685..
- 14Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Mov Disord. 1987;2:237-254., , , et al.
- 15Management of spasticity associated pain with botulinum toxin A. J Pain Symptom Manage. 2000;20:44-49., , , et al.
- 16Prophylactic treatment of chronic tension-type headache using botulinum toxin type A. Eur J Neurol. 1999;6(Suppl 4):S99-S102., , , , , .
- 17Botulinum toxin: New treatment for temporomandibular disorders. Br J Oral Maxillofac Surg. 2000;38:466-471., , .
- 18Botulinum toxin in the treatment of myofascial pain syndrome. Pain. 1994;59:65-69., , .
- 19Botulinum toxin A and chronic low back pain: A randomized, double-blind study. Neurology. 2001;56:1290-1293., , , .
- 20Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008;64:274-283., , , .
- 21A double-blind, randomized, placebo-controlled comparison of botulinum toxin type a injection sites and doses in the prevention of episodic migraine. Pain Med. 2007;8:478-485., , , , .
- 22A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis. J Pain. 2006;7:688-696., , , , .
- 23A multicentre, double-blind, randomized, placebo-controlled, parallel group study of multiple treatments of botulinum toxin type A (BoNTA) for the prophylaxis of episodic migraine headaches. Cephalalgia. 2007;27:492-503., , , , , .
- 24Botulinum toxin type A for the prophylactic treatment of chronic daily headache: A randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2005;80:1126-1137., , , , , .
- 25Botulinum toxin type A prophylactic treatment of episodic migraine: A randomized, double-blind, placebo-controlled exploratory study. Headache. 2007;47:486-499., , , , .
- 26Botulinum toxin type A in the prophylactic treatment of chronic tension-type headache: A multicentre, double-blind, randomized, placebo-controlled, parallel-group study. Cephalalgia. 2006;26:790-800., , , et al.
- 27OnabotulinumtoxinA for treatment of chronic migraine: Pooled results from the double-blind, randomized placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50:921-936., , , et al.
- 28OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30:793-803., , , et al.
- 29OnabotulinumtoxinA for threatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30:804-814., , , et al.
- 30Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005;26:785-793..
- 31Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache. 2003;43(Suppl 1):S9-S15..
- 32Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107:125-133., , , .
- 33Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: Implications for migraine therapy. Headache. 2004;44:35-42., , .
- 34Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: Involvement of two distinct mechanisms. Biochem Pharmacol. 2000;59:1403-1406., , , .
- 35Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon. 2000;38:245-258., , .
- 36The effects of botulinum toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization. Pain. 2006;122:315-325., , , .
- 37Subcutaneous botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin. Pain. 2009;141:60-69., , , , .
- 38Botulinum toxin type A (BOTOX) for treatment of migraine headaches: An open-label study. Otolaryngol Head Neck Surg. 2000;123:669-676., , , , .
- 39Botulinum toxin type a for the prophylaxis of chronic daily headache: Subgroup analysis of patients not receiving other prophylactic medications: A randomized double-blind, placebo-controlled study. Headache. 2005;45:315-324., , , , , .
- 40Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia. 2008;28:484-495., , , et al.
- 41Committee for Medicinal Products for Human Use. Guideline on clinical investigation of medicinal products for the treatment of migraine. http://www.emea.europa.eu/pdfs/human/ewp/078801enfin.pdf. Accessed June 7, 2010.
- 42International Headache Society Committee on Clinical Trials in Migraine. Guidelines for controlled trials of drugs in migraine. First edition. Cephalalgia. 1991;11:1-12.
- 43The prophylactic treatment of chronic daily headache. Headache. 2006;46:1552-1564..
- 44
- 45FRAMIG 2000: Medical and therapeutic management of migraine in France. Cephalalgia. 2005;25:267-279., , , .
- 46Influence of disease features on adherence to prophylactic migraine medication. Acta Neurol Scand. 2008;118:367-372., , .
- 47Migraine prophylactic medication usage patterns in The Netherlands. Cephalalgia. 2003;23:293-301., , , , .
- 48Treatment of chronic cervical-associated headache with botulinum toxin A: A pilot study. Headache. 2000;40:231-236., .
- 49Treatment of chronic tension-type headache with botulinum toxin A: A randomized, double-blind, placebo-controlled multicenter study. Pain. 2004;109:110-114., .
- 50BOTOX® (Botulinum Toxin Type A) Full Prescribing Information. Irvine, CA: Allergan, Inc.; 2006.
- 51Procedures for administering botulinum toxin type A for migraine and tension-type headache. Headache. 2003;43:884-891., , , .
- 52GaAs laser treatment of bilateral eyelid ptosis due to complication of botulinum toxin type A injection. Photomed Laser Surg. 2008;26:507-509..
*Some data presented here on dosage per muscle, muscle groups, and rates for specific AEs were not detailed in these primary publications.
- i
Historically, three terms have commonly been used interchangeably to describe patients with very frequent headaches that occur on most days of the month. These terms are chronic daily headache, transformed migraine, and chronic migraine. In June 2006, the Headache Classification Committee (ICHD) of the International Headache Society published revised criteria for diagnosing CM (ICHD-2R) and confirmed their position that chronic migraine was the preferred terminology among the three.3


text:
Item details
Qty Available
Only one in stock, order soon
Country/Region Of Manufacture
United States
This item has been added to your cart
Sheet Music I Don't Care What You Use To Be Dixie Hamilton 1924 Dubin McHugh added to cart. Only one available in stock
View Cart
or continue shopping.
View Cart
or continue shopping.
Please wait while we finish adding this item to your cart.
Added to your wish list!
- Sheet Music I Don't Care What You Use To Be Dixie Hamilton 1924 Dubin McHugh
- 1 in stock
- Ships within 2 days. Estimated delivery: Wednesday, June 1st
- Add to cart
Do you have any questions for the seller?
More about this item
Listing details
Seller policies
Shipping discount
Shipping weights of all items added together for savings.
Posted for sale
More than a week ago
Item number

subset: commoncrawl


text:
CPL money stolen in Trinidad
PORT-OF-SPAIN, Trinidad, CMC-Close to TT200,000 dollars from ticket sales of upcoming matches in the Caribbean Premier League (CPL) have been stolen, Police in Trinidad and Tobago have said.
The money, for three CPL matches scheduled for this week starting Thursday, was stolen from the ticketing office of the Queen's Park Oval in Port-Of-Spain, between Saturday evening and Sunday morning, investigating officers have reported.
The Police also confirmed that an official report was made by Queen's Park's ticketing co-coordinator Karen Bynoe.
Media reports here quote investigating officers as saying Bynoe placed the money in an envelope and secured it in a drawer at around 5 p.m. on Saturday, but could it could not be found when she went in search of it on Sunday.
An envelope with a number of cheques also in the drawer was untouched, said police.
Police believe the robbery was an inside job since the door to the general office was not tampered with, but the one leading to the office where the money was kept was broken into.
A number of people have been questioned, but no arrest has been made.
"CPL can confirm that there is an investigation currently underway regarding an issue with tickets," said CPLT20 media officer for Trinidad and Tobago, Abigail Edwards.
"However, it cannot comment further until such a time as the relevant authorities have completed their enquiries."


text:
|This thread has been locked, it will not receive new replies.
Locked on 11/03/2010 7:39:40 PM PDT by Religion Moderator, reason:
Duplicate: http://www.freerepublic.com/focus/f-news/2620857/posts
Skip to comments.Speaker Nancy Pelosi Says She Has 'No Regrets'
Posted on 11/03/2010 5:39:05 PM PDT by Fred
House Speaker Nancy Pelosi said today she has "no regrets" one day after a Republican landslide stripped her of the power that defined her historic tenure as the first female speaker of the House.
The California Democrat, who won a new two-year term in Tuesday's election, said she has yet to consider what she will do now.
"I'll have a conversation with my caucus, I'll have a conversation with my family, and pray over it, and decide how to go forward," she said in an exclusive ABC News interview with "World News" anchor Diane Sawyer. "But today isn't that day."
(Excerpt) Read more at abcnews.go.com ...
Of course not, she's still a lunatic.
Look, whatever Nancy says, just think the opposite, because everything she is saying is a total lie.
of course she has no regrets.
0bamacare IS LAW.
CZARS are IN PLACE.
till those+ are un-done...she's/they've won!
of course she has no regrets.
0bamacare IS LAW.
CZARS are IN PLACE.
till those+ are un-done...she's/they've won!
Rush predicted this back in 2007. I remember because I was living in NH at the time and the democrats just won the house and there was a lot of talk by the dems about how much they wanted to do to... I mean "for us".. and they seemed hell bent on jamming it through in spite of the feelings of the electorate.
Amen. 100% correct. Also applies to the Silver Tonued Sociopath, Obama.
Amen. 100% correct. Also applies to the Silver Tongued Sociopath, Obama.
With 20 dem senate seats up for grabs in 12, lets hope so. Keep talking dems, let it all hang out, let us have it, emulate Grayson....LOL!
She's either a liar or an honest sociopath.
Neither do we, *unt.
Keep looking over your shoulders "biach".
Someone like me would love to give you a swift kick from time to time (just to remember us by).
Of course we all know about condemned criminals making similar statements right before the switch is flipped.
I'd like to see her ugly face when they take away her airplane keys.
Interesting that she actually entertained the possibility of rolling back parts of the healthcare bill. Said that there are certain parts that both side may want to change and how they'd debate piece by piece. Writing's on the wall.
Brian Sussman (conservative Bay Area talk show host) has been saying for weeks/months now that she'll end up running for, and becoming, mayor of San Francisco.
Sounds like as a good a theory as any.
I love that they don't get what happened.
We can do it again in two years.
Pelosi has no regrets.
Me neither.
Neither does OJ.
At the close of business on Jan. 4, 2007, Pelosis first day as speaker, the national debt was $8,670,596,242,973.04 (8.67 trillion), according to the Bureau of the Public Debt, a division of the U.S. Treasury Department. At the close of business on Oct. 22, it stood at $13,667,983,325,978.31 (13.67 trillion), an increase of 4,997,387,083,005.27 (or approximately $5 trillion).
Pelosi, the 60th speaker of the U.S. House of Representatives, has added more to the national debt than the first 57 House speakers combined.
The $4.997-trillion increase in the national debt since she took the gavel is more debt than the federal government amassed from the speakership of Rep. Frederick Muhlenberg\ of Pennsylvania, who became the first speaker of the House on April 1, 1789, to the start of the speakership of Rep. Newt Gingrich of Georgia, the 58th speaker, who took up the gavel on Jan. 4, 1995.
thanks for reminding me! Murderer OJ sleeps in jail now every nicght, likely for the rest of his life.
I actually knew him in Buffalo- and knew a bit about the behind the scenes stuff. The wife drove him insane- but he killed her then destroyed other people defending himself.
Interesting! What did OJ's wife do to drive him crazy?
Is she *Still* absolutely certain that the Democrats are going to retain control of Congress? If not where is her explanation of what happened and how she was mislead?
That's the best picture of Nan I've seen in a long time. lol
Of course she doesn't have any regrets. Neither did Hitler.
Note to Pelosi: Pray all you want. You're going to burn for what you did to this country, you gutless, crazy POS.
"Every week we don't pass a Stimulus package, 500 million Americans lose their jobs.' ~ Nancy Pelosi.
The gavel of the speaker of the House is in the hands of special interests, and now it will be in the hands of Americas children. ~ Nancy Pelosi, on the prospect of Democrats winning back Congress.
....regrets...she's had a few...but then again....the paper won't mention...
I despise that woman even more than I do Obama.
She did all the damage she intended to do. Mission accomplished.
Yes, to whom does she pray? Joseph Stalin?
"Id like to see her ugly face when they take away her airplane keys"
I'd pay good money to see that!
Here's a link to some pictures of a few of Nancy's constituents, celebrating her victory...
Is she going to bring her grandchildren to DC to watch her get kicked out of her Speakership?
Nancy I can't wait to see you have to fly commercial again!
I dunno man, It's starting to feel kinda like beating up a retarded kid in a wheelchair. At some point I think we are gonna have to ask God to forgive us.
I have some suggestions as to "what she should do": Hit her self in the head with her enormous gavel one last time, Stop tasking obscene amounts of botox daily, Save her family further embarrassment by disappearing, Become a maid for mooch-elle nobama, Apologize to America by resigning immediately and the going to the slums of Mumbai and taking care of the indigent, Have a task for the rest of her life of kissing every citizens' ass. I can only dream about this corrosive fool.
I would believe that she would run for mayor. Gavin Newsom was elected Lieutenant Governor of California, so he's leaving office as mayor soon. Don't know if S.F. will have a special election to replace him or what will happen. I think the next regularly scheduled mayoral election is Nov. 2011 in S.F. for local elections there.
Nancy could well win an election in S.F. because she will be right at home with her liberal base.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.


text:
Inner-Strength Builds Confidence
Just like everyone else in America, I come from a dysfunctional family.
I graduated from high-school at 16, got accepted and attended college and majored in Early Childhood Education only to have my own education become a casualty of my parent's divorce. I'll spare you the sordid details except for the ones that are necessary for this article.
At the ripe old age of 17, I found myself homeless and uneducated, unable to get a job, moving from relative to relative. It seems that one does not qualify for financial aid when one is a minor child of a prominent physician. It also seems that if one sits out of school for more than two terms, one is no longer considered a college student and therefore is not entitled to tuition. Hooray for the state of Illinois.
My mother had no job, no money and three younger children to feed. Luckily she had packed her deep freeze with produce and a half a cow the summer before or they would have starved. I would have merely become another burden for her to bear…
Read more: http://living4bliss.wordpress.com/2012/04/04/inner-strength-builds-confidence/
Via living4bliss.wordpress.com
Tags: Early childhood education, Education, FAFSA, High school, Illinois, Student, Student financial aid in the United States, United States0


text:
First video of Reef/Fish tank
Started Oct 28, 2012 | Discussions thread
Shop cameras & lenses ▾
Larry251 • Contributing Member • Posts: 629
Re: First video of Reef/Fish tank
I like it! Seems like a great start. What software did you use for editing?
It's a little disheartening. I think you got your 5N around the same time as I got mine and you seem to have done SO much more with it. I just haven't had the time Oh well, I'll get there
Larry251's gear list:Larry251's gear list
Sony Alpha NEX-6 Sony a6000 Sony E 55-210mm F4.5-6.3 OSS Sony E 10-18mm F4 OSS Sony E 16-50mm F3.5-5.6 PZ OSS +2 more
Reply Reply with quote Complain
|Post ( )
|Posted by
|Oct 28, 2012
|Oct 28, 2012
Keyboard shortcuts:
FForum PPrevious NNext WNext unread UUpvote SSubscribe RReply QQuote BBookmark MMy threads
Color scheme? Blue / Yellow


text:
Thanks for your answer. More info. My car has about 65,000 miles on it. It has a short ram air intake, new. I have already fouled 3 sets of spark plugs, so I know that there is a lot of fuel getting to the cylinders. I unplugged the injectors and the car started. When the fuel was burned off, I plugged the injectors back in. The car spins over easily but still will not start. Any thoughts now.
by golfman in Burlington, NC on February 02, 2009


text:
- KenyaFoodFunding via Yehu Microfinance Trust
AishaKenyaFoodFunding via Yehu Microfinance Trust
MwanamkasiKenyaFoodFunding via Yehu Microfinance Trust
Update on EshaEsha is asking for a loan because she believes that through it, she will improve her food stall business.
The previous loan enabled her to save money in her business. She is requesting a loan of 30,000 KES to purchase food ingredients like onions, tomatoes and rice for her business.
She feels that she was able to make a good investment with her previous loan which, to date, has allowed her to maintain her level of profits to help her family cover their personal expenses
Previous Loan DetailsEsha, who is 34 years old, is a widowed mother who takes care of four children. Thanks to her efforts and hard work, she has been able to take them to school. For the past two years, Esha has been running a food stall that is home-based. She sells a variety of African dishes. In the past f... More from Esha's previous loan »
Additional Information
About Yehu Microfinance TrustThis loan is administered by Yehu Microfinance Trust, which was founded in 1998 as a project of CHOICE Humanitarian Kenya. In July 2007, Yehu became a separate entity from CHOICE and was registered as a trust. Since then, Yehu has expanded to cover over half of Kenya's 13 coastal districts.
Concurrent and Successive Loans
Our Field Partners often work with borrowers over a series of loans as the borrowers build credit, take out bigger loans, and expand their businesses. In order to make it easier for our Field Partners to post loans for borrowers who have been listed on Kiva before, we allow them to post successive and concurrent loans for their Kiva borrowers. This means that our Field Partners are able to post a borrower's second, third, etc., loan on Kiva without having to re-enter all of the borrower's information.
This borrower has been listed on Kiva before, so you'll see an updated loan description, as well as excerpts of the original descriptions from earlier loans. Most borrowers take out loans consecutively, meaning that they receive a second loan after having repaid the first. However, sometimes our Field Partners give out concurrent loans, allowing borrowers to take out one primary loan and a secondary "add-on" loan along with it. These "add-on" loans are typically smaller than the borrower's primary loan and serve a different purpose. Because Field Partners can now post loans as successive and concurrent loans, you will be able to track borrower progress over time and see the various ways a borrower is working with our Field Partners through funds from Kiva's lenders.
Loan tags help lenders find loans that match certain areas of interest. You can add up to 5 tags for this loan.
About Kenya
408View loans »
Success!! The loan was 100% repaid
- Repayment Term
- 14 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Sep 20, 2013
- Listed
- Oct 7, 2013
- Currency Exchange Loss:
- Possible
- Ended:
- Oct 17, 2014
Photo from previous loan
Kiva allows our Field Partners to re-use the same photo for individual borrowers that have been posted on Kiva's website once before in a 24 month period, and we allow them to re-use group photos for up to 24 months, provided that 80% of the current group's membership is represented.
Taking, collecting, and uploading photos of borrowers is one of the most challenging elements of using Kiva for our Field Partners. In order to make Kiva easier for Field Partners to use, we have allowed them to post successive and concurrent loans without taking a new photo of the borrower if the criteria above are met.


text:
Jews for Jesus Israel Director Dan Sered | Next Steps After Barry Barnett Release
Unfortunately, Barry has been issued an expulsion order from the office of the Ministry of the Interior. We will be fighting this order through the courts in Israel. More to follow on this in the weeks ahead.


text:
A lot of people are afraid of heights. Not me, I'm afraid of widths.
-Steven Wright
Read more at http://www.brainyquote.com/quotes/authors/s/steven_wright.html#vyUOz6BGb3EYCGGS.99 - Steven Wright
Bernina 830LE - Brother Dreamweaver VQ3000 - Bernina B530 - Janome 6600P - Pfaff 1209 - Babylock Evolution - Janome 644 - Babylock Sashiko2 - Babylock BLCS-2
------Stash: 202.625 yds. @ 04.17.16
------"Play the cards you are dealt, but choose who is sitting at the table"..AARP magazine
SEE MY ETSY SHOP HERE: http://www.etsy.com/shop/AuntMaymesAttic
My blog: http://auntmaymesattic.wordpress.com/
------"Improvise, adapt and overcome." - Clint Eastwood/Heartbreak Ridge
"Isn�t it a shame in today�s world you can�t tell the truth. If you tell the truth you�re abrasive. If you lie you�re charming." - Bob Huggins/College Basketball Coach
------it doesn't matter what type of sewing you do. you are sewing, and sewing is good.
------Impossible you say? Nothing is impossible when you work for the circus!
Let's make Better Mistakes Tomorrow
------Erin "Debbie" Wilson
A variety of machines I love for different reasons but a real sucker for beautiful Bernina Tula Pink 350
------Babylock Ellisimo Gold
Babylock Enlighten
Kenmore 1914
Kenmore 1814
* Advertising and soliciting is strictly prohibited on PatternReview.com. If you find a post which is not in agreement with our Terms and Conditions, please click on the Report Post button to report it.
Class Details
by: AmberSage
Pattern Details
by: popo
Online Classes
Sewing Machines
Sign Up
Shop Now
Merchant Gallery
Conditions of Use | Posting Guidelines | Privacy Policy | Shipping Rates | Returns & Refunds | Contact Us | About | New To PR | Advertising
Copyright © 2016 PatternReview.com® , OSATech, Inc. All rights reserved.


text:
Manufacturing Area
Category: Candles
1.led candle 2.Materil: paraffin wax 3.Color: Multi-colored 4.Shape:pillar/ flower/free shape 5.For home party/bar decorKeyword : LED electric candles | flameless led candle | led wax candle | Real Wax LED candle
Category: Metal candle holders
Metal led candle Lantern: 1. size:metal lantern size:18cm*18cm*54cm,plastic led candle size:D7.5cm*H11.5cm 2. color:black or can be customized 3. material:metal+plastic/wax led candle 4. finish: pow ...Keyword : Metal LED Candle Lantern | Battery Operated LED Candle Lantern | Flameless LED Candle Lantern | LED Candle Lantern | Home Decoration LED Candle Lantern
Moving Flame Wick Flameless led candle with timer: flameless, moving wick, timer, battery operatedKeyword : led candle | flameless led candle | moving wick candle | led candle timer | candle
CHZ Enjoy candle's life! CHZ design and manufacture Flameless led candle with timer selling to QVC with Home Reflection Brand from 2008 which enjoys good quality reputation. CHZ candle modules are ...Keyword : flameless LED candle | multi color LED works with 2pcs C batteries | LED candle with timer | wax candle | LED candle
Category: LED Lights
‧ Input Voltage:AC100~240V . ‧ Base Type:E14/E26/E27/GU10/GU5.3/MR16. ‧Optional PC Cover:Mist / Transparent G40: ‧ Beam Angle:150°. Keyword : LED Candle Light | led candle light bulbs | led candle lights wholesale | led candle lights with timer | led candle lights with sensor
Type: led candle Material: Paraffin Wax Feature: Flameless Handmade: Yes Use: Home Decoration 4 hours timer cycle: 4hours on, 20 hours off; 8 hours cycle: 8 hours on, 16 hours off; ...Keyword : LED candles | flameless candle light | LED power
Product Description Set of 3 Remote Control Battery Operated Color Changing Flameless candles 4, 5, and 6 Inch with multi function remote. Control these candles from across the room, use the controlle ...Keyword : Remote Control Candle | Flameless Candle | Flameless Led Candle | Electronic Led Candle | Candle Gift
Battery Operated Wax led Light candle lamp (RCL-0012) led candle,led candles,Battery led candle,Wax led candle,Lamp led candle,Battery led candles,led Battery candle We specialized in candle since 198 ...Keyword : Led Candle | Led Candles | Battery Led Candle | Wax Led Candle | Lamp Led Candle
Dia3"x4",3"x6",led Wax candle with timer (Time is adjustable according to customer request before order), works with C sizes battery (battery excl.) led candles,stable and realistic looking,f ...
we are a professional candles from China, we good at led candles, this candle we have different size: Diameter: 2" hight 2", 3", 4",5" and 6" Diameter: 3" hight: 3",4",5" and 6" Diameter: 4" hight: 4" ...Keyword : led candle | flameless candle | real wax led candles | scented led candles | battery operated candle
Category: Candles,Tapers
Product name Marilyn Monroe Stick led Flameless candle for Window Decoration Model Item STZ05 Materials Paraffin wax and ABS Product size DIM3"*H4" , or customized Shell color Black, or customized L ...Keyword : Flameless Candle
Soft Flameless led candle Tealight 1.Battery:1pcs 2032 battey 2.Material:PP 3.Color:Many different colors Specification Color :red , yellow , blue , green , white and color changing light, ...Keyword : LED Candle Tealight | LED electroSoft Flameless LED Candle Tealightnic candles | Soft Flameless LED Candle Tealight | LED electronic candles | LED candles
Category: LED Home Lighting
1. Aluminum PCB ,fireproofing, stronger heat dissipation. 2. Lamp shade with acrylic material of antistatic processing. 3. Chip with high power SMD3014,more natural lighting. 4. E14 base , suitab ...Keyword : led candle bulb | 3w/5w led candle bulb | e14 3w/5w led candle bulb | white/warm white led candle bulb | led bulb
Our main products are Car led Light,and led Bulb Light Car led Light as follow: led Strip Light,led soft Light,led Side View strip ,led underbody Light,led Car illumination,led Fog Light, ...Keyword : LED Candle Light | LED Candle Bulb | Candle Light | LED Decorative Light | LED Light Bulb
Category: LED Bulbs
3W E14 led candle bulb 1.Power:3W 2.led quantity:3PCS 3.specification:E27/E14 4.luminous flux:white≥260LM ...Keyword : led candle bulb | e14 led candle bulb | 3w e14 led candle bulb | led candle light | 3w led candle light
Quick Details Light Source: led Item Type: Bulb Lights led Light Source: SMD Type: candle Lights Input Voltage(V): 85-265 Lamp Power(W): 4 Lamp Luminous Flux(lm): 340 Lamp Luminous Efficiency(lm/w): ...Keyword : led
Model: led candle light RD-4016 Size: 26*127mm (dia. *length) Power: 3W Input voltage: 85-265VAC led quantity: 3pcs 1Watte Color Temperature: 2800-3200,4000-4500,7000-7500K Brightness: 260-290lm ...Keyword : frosted led candle light | high power led candle light | indoor led light | brightness led candle lamp | E14 led candle lamp
Model: led candle light E14-4WN Size: 43*151MM (dia. *length) Power: 4W Input voltage: 85-265VAC led quantity: 4pcs 1W Color Temperature: 2800-3200,4000-4500,7000-7500K Brightness: 360-400Lm Lu ...Keyword : brightness led candle light | high power led candle light | E14 led cadle lamp | E14 led candle light | New design led candle bulb
glass candle 4w led. ra.80. 2 years warranty. 350lm.Keyword : led candle 4w | 4w led candle | led 4w bulb
Feature of led candle light 1. Long lifespan, more than 40,000 hours 2. Low electricity consumption 3. higher lumen output, lower power consumption, 4. Constant current drive power, safe and rel ...Keyword : led candle light | led candle lmap | led bulb light


text:
I have a 2006 for taurus with a transverse mounted V6. I have been getting a mettallic rattling from the area around the serpentine belt, with some fluid leaking/dripping from the area near the lower pulley. It's been whipping off the pulley system and onto the firewall, frame and the exhaust pipes, burning with a sweet smell with no smoke. I did a 'color test' but dabbing some onto a white paper towel and then 'sampling' the car's fluids but I cant tell what it is by sight or smell. (I dont wanna do a taste test!) I'm looking for some suggestions as what to do - this car has 80k miles on it, and I drive 70 miles a day round trip to go to school so I can't have too much down time on it. I'm ok working on it as long as it's not too in depth - Chilton's is my bible, but they dont have one out for this model yet. Any help is greatly appreciated!
rattling coming from engine with small leak on 2006 Ford Taurus
by Nox in Grants Pass, OR on May 09, 2010
Get Your Car Fixed at a RepairPal Certified Shop.
We certify shops based on expertise, quality work, and verified customer reviews
1 answer 1 comment
ANSWER by dandd , May 09, 2010
The sweet smell is most likely coolant. You should check for a cooling system leak, possibly from your water pump which would explain why it is being slung on to the firewall.
COMMENT by smoore5190 , February 22, 2011
I have same problem but no leaking. Could it be my AC pulley? Tested the belt tension and the AC pulley seams to be a little loose. What happens if this goes out?


text:
Meal Type
Featured Videos
Featured Content
Featured Brand Sites
Product By Category
Tools & Info
Cooking Tips
Healthy Living
Your Kids
food&family Magazine
Tap or click steps to mark as complete
I made this cake for a dinner I had but I used Spice cake mix instead of the yellow cake mix. It was great and I gave the recipe to quite a few of my guests.
I have actually made this receipe twice. My family enjoyed it very much. The second time I made it I used the pumpkin pie mix instead of the pure pumpkin; leaving out the sugar and spices. It had a little more of the pumpkin pie taste. Very good recipe for pumpkin lovers.


text:
Click here to email Dr. Jacobs directly.
Dr. Dan Jacobs is on the Core Faculty in William James College's School Psychology Department (MA/CAGS and PsyD programs) and also serves as an adjunct faculty member in William James College's Clinical and Leadership Psychology Departments. Dr. Jacobs is a licensed clinical psychologist with over 15 years of experience working with individuals, families, programs and systems. Dr. Jacobs is a graduate of William James College's Clinical PsyD Program and also has earned an EdM from Harvard University and an MBA from Salem State University. He has worked as an internal and external consultant to primary and secondary schools, hospitals, and residential programs regarding counseling and intervention concerns. He has also worked with organizations and agencies (e.g., Department of Children and Families, Department of Mental Health, Massachusetts State Police Department, local municipal police departments) providing training, testing and/or consultation services. Dr. Jacobs was formerly the Director of Sub Acute Services at NSMC/Salem Hospital in Salem, MA and developed and ran the Adolescent and Adult Partial Hospital Programs, which helped adolescents, transitional age youth, and adults with significant mental health and dual diagnosis concerns. He was responsible for all program planning, budget, hiring and training concerns and also served on the medical center's Medical Records and Manager Leadership teams and actively participated in internal qualitative reviews and in external JCAHO (now Joint Commission) accreditation processes of his programs.
In the past 10 years Dr. Jacobs has delivered over 150 professional Continuing Education trainings on issues of child and adolescent psychopathology, individual and family counseling, dual diagnosis, crisis management, system improvement, ethics, and behavior change. Dr. Jacobs is very interested in finding ways to improve effectiveness in all types of systems. He also has a private practice in Andover, MA at Jacobs Psychological & Consulting Services and works with children, adolescents, adults and families challenged by mental health and substance abuse concerns and also works with adults exploring professional growth and mid-career change options. Dr. Jacobs is a member of: The American Psychological Association (APA), the National Association of School Psychologists (NASP), The Massachusetts School Psychologists Association (MSPA), the Society for Police and Criminal Psychology, and Division 18 of the APA (Psychologists in Public Service).
Open Houses and Webinars
Continuing Ed Calendar of Programs
Doctoral Projects & Colloquia Schedule
Weekly News Around Campus
Academic Calendar


text:
This one really works well
Great if your not expanding the handsets
If you find ReviewGist useful let us know by liking our Facebook page below.
ReviewGist helps you find the best products to buy by making sense of online reviews.
We are currently aggregating 374,044 reviews
covering over 29,392 products. See what the press says about ReviewGist here.
Best Smartphones under Rs. 10,000
© 2007-16 ReviewGist.com. All Rights Reserved.


text:
: [Pokémon]
A Smell of Petroleum Pervades Throughout
View Single Post
February 17th, 2013 (3:19 PM).
Adin Terim
Absolutely Insane
Join Date: Oct 2012
Nature: Adamant
Posts: 61
Loot the Professor's desk, look for something to hold That Thing's pokeball shut. Check the bookcases for information on Eldritch form pokemon. You should probably go back and loot the other houses too.
sketch'd & scan'd
It's a Crazy World - A Randomized Nuzlocke
Change - A Pokemon Story
Don't take life too seriously. It's only a temporary condition.
Adin Terim
View Public Profile
Send a private message to Adin Terim
Find all posts by Adin Terim
Find threads started by Adin Terim


text:
The nation's largest gay rights magazine has ranked Spokane as the third-gayest city in the nation.
Two other Washington cities made the top five, including Seattle at No. 5 and Tacoma leading the way as the gayest city in the nation.
The news of a No. 3 ranking came as a happy surprise to Marvo Reguindin, general manager of the Inland Northwest Business Alliance, the chamber of commerce for gay businesses and those allied with them.
"I think it's great," Reguindin said. "Knowing that we're No. 3, we'll definitely be able to use that to our advantage."
The rankings, released Wednesday by The Advocate, assessed cities based on how many openly gay representatives the city has at local, state and federal levels, as well as whether gay marriage is legal in the state and how many companies on the Human Rights Campaign Foundation's Corporate Equality Index are based in the city.
The criteria also included whether the cities had good shopping, roller derby leagues, protection for people who are transgender, gay rugby teams and bisexual resource groups.
Cities also earned points for hosting concerts by the Scissor Sisters, Uh Huh Her, Girl in a Coma and the cast of Glee.
Spokane earned most of its points through being in a state that recognizes gay marriage and has seven openly gay representatives, but it picked up extra points for its hosting of the Spokane Pride Parade and the Rainbow Festival every year through Out Spokane.


text:
It has run here on the site several times now. The general conclusion each time was that the shooting was justified.
This is a discussion on James Boyd Shooting within the Carry & Defensive Scenarios forums, part of the Defensive Carry Discussions category; Anyone following the James Boyd Murder in Albuquerque? I would have posted a link but couldn't get it to take. After viewing the video, I ...
Anyone following the James Boyd Murder in Albuquerque? I would have posted a link but couldn't get it to take. After viewing the video, I call BS. It's murder by police.
It has run here on the site several times now. The general conclusion each time was that the shooting was justified.
OK, I just heard about this and watched the video. Boyd did have a knife in each hand BUT, he had actually turned away from the police as if he was going to "flee" before the first shot was fired. (Though how far are you going to go with a swat team on your six? ) I suppose that you "could " justify this because he had a weapon in his hands and was not following the police instructions. Could this have been handled differently??? I would have to say yes!! How long did they try to de escalate the situation? Mr Boyd looked confused to me in the short video. Many homeless are dealing with health and mental issues and if these guys are trained to be on the response team they should be trained to handle situations like this a little better than that! Handling situations in this manor
is what makes the public NOT trust the police.
Capital punishment for unauthorized camping.
I'm just a spoke in the wheel but not a big deal.
America...a Constitutional Republic. NOT a democracy as the liberals would have us believe.
PANTS UP DON'T LOOT!!....A Kentucky Rifle behind EVERY BLADE OF GRASS!!
You know that look women give you when they want some sugar? Me neither
I did NOT...NOT...NOT see the tape but if a guy only has knives wouldn't you be close enough that a Tazer could take him out?
If memory serves they had tried to tazer and bean bag rounds from a shotgun which didnt work. I dont really understand why a SWAT team was deployed. Also he didnt pull the knives until the dog was sent in and bit him. Up to that point he apparently had only argued with officers and in the video was packing up to leave the area.
He clearly isnt charging the officers when they fired but turning to run. There will be no charges over it if for no other a reason a dog used by police is considered the same as a human police officer so I imagine that is the excuse they will use to legally justify the shooting as the dog was in close to the victim. I sort of have a problem with a dog being on the same level as a human police officer but it is what it is.
Legally right or wrong it will be justified. I wasnt there but from what I saw in the video it could have been handled alot better than it was.
You dont have to believe a train is coming. Itll run over you anyway.
It looked awkward to me..
Would I have been in on the party there to escort him out/off the public land?
No. I would have told my chief I felt very ill, and needed to go home.
I didn't see all they saw though, but he was on public lands, not occupied by anyone.
It wasn't like he was squatting in the downtown district for cripes sake.
I would rather die with good men than hide with cowards
If you want to make God laugh, tell him your plans.
"Politics is the art of looking for trouble, finding it whether it exists or not, diagnosing it incorrectly, and applying the wrong remedy."
M&Pc .357SIG, 2340Sigpro .357SIG
Video is only 1/2 the equation in any scene. You have to also consider what Boyd was saying and when he said it. Given the audio, it becomes a totally different scene. Have you heard it?
This thread does not meet the standards for this forum section:Closed.Real or hypothetical, discussions regarding when you should or should not draw your weapon, shoot or not shoot, attack or retreat is valuable to each of us.
Fortes Fortuna Juvat
Former, USMC 0311, OIF/OEF vet
NRA Pistol/Rifle/Shotgun/Reloading Instructor, RSO, Ohio CHL Instructor


text:
Shapeways: Bring your creativity to life in 3D http://www.shapeways.com/forum/index.php Shapeways: Bring your creativity to life in 3D Calculation is off? http://www.shapeways.com/forum/index.php?t=rview&goto=13569&th=2709#msg_13569 <![CDATA[I uploaded a project I'm working on and have some questions about it. The object itself is hollow, it's a case for a device I'm working on. However I think the Shapeways system seems to think it's a solid object and the price is like $1400 for a 9"x9"x3.25" hollow object. Am I missing something here? http://www.shapeways.com/model/128033/case_take_1.html

 I was kinda expecting it to cost less as 938cm3 is a little much. Any ideas?]]> Caponata 2010-06-10T23:06:27-00:00 Re: Calculation is off? http://www.shapeways.com/forum/index.php?t=rview&goto=13580&th=2709#msg_13580 <![CDATA[Mmmm...Houston we might have a problem. Could you email your file to service@ so they can take a look at it.

 Joris
 ]]> joris 2010-06-11T04:52:54-00:00 Re: Calculation is off? http://www.shapeways.com/forum/index.php?t=rview&goto=13621&th=2709#msg_13621 <![CDATA[Email is sent, haven't heard back yet. ]]> Caponata 2010-06-11T23:21:17-00:00 Re: Calculation is off? http://www.shapeways.com/forum/index.php?t=rview&goto=13622&th=2709#msg_13622 <![CDATA[Does it have a hole in it? If not, the new uploader prices it like a solid object. Just a guess ...]]> gibell 2010-06-11T23:35:10-00:00 Re: Calculation is off? http://www.shapeways.com/forum/index.php?t=rview&goto=13623&th=2709#msg_13623 <![CDATA[It's got 4 holes in fact. I'm guessing it's pricing it like a solid. ]]> Caponata 2010-06-12T01:32:10-00:00 Re: Calculation is off? http://www.shapeways.com/forum/index.php?t=rview&goto=13768&th=2709#msg_13768 <![CDATA[That could be what it is.

 ___________________
 Watch movies online free]]> flammableeye 2010-06-17T17:59:50-00:00


text:
--- Operating System, Graphics card ---
--- Blender version with error, and version that worked ---
--- Short description of error ---
The content length header is depended upon to show status in modern downloading programs, including browsers. It's nice to distinguish between being 95% complete, or 3% complete when downloading a file.
e.g. wget ouput
--2013-01-03 15:54:40-- http://projects.blender.org/tracker/download.php/153/467/29714/23287/sun_position.zip
Resolving projects.blender.org (projects.blender.org)... 188.8.131.52
Connecting to projects.blender.org (projects.blender.org)|184.108.40.206|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: unspecified [application/x-zip-compressed]
Saving to: `sun_position.zip'
--- Steps for others to reproduce the error (preferably based on attached .blend file) ---
Download a file from projects.blender.org, e.g., http://projects.blender.org/tracker/download.php/153/467/29714/23287/sun_position.zip
wget is the best tool for this because it lets you see the headers. Otherwise Google Chrome Dev Tools' network panel will let you see response headers.
Closed, InvalidPublic
- Assigned To
- None
- Priority
- Normal
- Author
- Sebastian Marie (sebbybear)
- Subscribers
- Sergey Sharybin (sergey), Sebastian Marie (sebbybear)
- Projects
- Type
- Bug
--- Operating System, Graphics card ---
Such kind of reports better be addressed to bugtracker's tracker http://projects.blender.org/tracker/?group_id=8 not to bug tracker about bugs in blender.
I can not mode this report there, so please go ahead and resubmit it to proper project,


text:
May 24, 2016
An Alford, Florida man is being held in the Jackson County Jail in Marianna for allegedly burning down his own home.
Darrel Burgess Young is being charged with one count of arson of an occupied dwelling.
Sheriff's officials say Young had an argument with other people living in the house and the allegedly set it on fire.
The incident happened around 4 a.m. Friday morning.
Jackson County Fire and Rescue was able to put the blaze out without any injuries to themselves or the residents of the home.
Click Here to access the online Public Inspection File
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or firstname.lastname@example.com.


text:
You need to upgrade your Adobe Flash Player to watch this video.
Download it from Adobe.
Download it from Adobe.
Obedient little sister has nothing to do with her brother`s
Submitted by Anonymous 1882 days ago
Subcribe to this video owner
- I like
this video39Thank you for voting!
- I dislike
this video13Thank you for voting!
Anonymous | 982 days - 22/09/2013
Anonymous | 1447 days - 13/06/2012
my 14yr. old sister and i have been fucking for a while now.the other day she brought home her 12year old girlfriend to fuck with us and i tell you i thought i died and went to heaven.


text:
FREE workshops!
Plan your Abilities Expo experience today!
Take advantage of Free Workshops that focus on everything from tips for traveling with a disability and the benefits of standing to how you can get the best accessible vehicle.
Workshops are FREE! All attendees are welcome – you don't need to register or sign up in advance. Just arrive early to the workshop to make sure you can get a seat!
There is so much more happening at Abilities Expo! Be sure to check out the FREE Events for demonstrations of adaptive sports, dancing, assistance dogs, horse therapy – and more. Most events include time for attendees to participate!
- Certificates of participation are available for all workshops. Please see the Accessibility Help Desk following each workshop for your certificate. (Please note there are no CEU approved courses at this year's Abilities Expo).
* Please note dates and times of workshops are subject to change without notice. Abilities Expo is not responsible for the materials or opinions of the speakers.
Here's what we did in 2015. Stay tuned for more information on 2016.
Friday, July 31, 2015
11:45am – 12:45pm
Wellness for People with Disabilities
Presented by Dr. Brandi Griffin, Chiropractor, Pearland Family Chiropractic
Location: Workshop Area
Chiropractic care is rooted in the belief that the human body naturally strives to maintain the highest level of health. When obstacles get in the way the result is disease. AT this workshop you'll discover what chiropractic treatment is, how it is used, and how it can work to improve your health. The present will also discuss other alternatives to the typical medical model including preventative health care, massage and rehabilitative exercise. Attendees will leave with ideas for how they can improve their health without drugs as well as home and recreational recommendations. Learn more at www.drbrandigriffin.com.
1:00pm – 2:00pm
Bionics: Not Just for the Privileged Few Any More
Jennifer French, MBA, Executive Director, Neurotech Network
Bionics and medical technology has come a long way in the last few years and becoming more accessible too. These life changing technologies are not only for those with mobility impairments but a wide array of disabilities. Did you know the Retinal Prosthesis or Bionic Eye to restore vision for those with retinitis pigmentosa has been approved for Medicare beneficiaries? Did you know that sacral nerve stimulation for incontinence has also been approved for Medicare payment? In this session, learn about amazing technologies for a variety of disabilities all featured in the recent book, Bionic Pioneers. Also, learn how to access the technology and whether it applies to you. Go beyond the limits of standard care and embrace the technology that can change your life. Learn more at www.neurotechnetwork.org.
* Book Signing! This workshop is followed by a book signing with Jennifer French from 2:15pm to 3:15pm. Copies of Bionic Pioneers (newly published in 2014) and On My Feet Again will be available for purchase. Special show prices of $20 per book or both books for $30. All proceeds benefit the Neurotech Network.
2:30pm – 3:30pm
Medicare Improvements for Patients and Providers Act of 2008: History, Benefits, Development, Critiques
Presented by Jessica Cassidy, Staff Attorney for Health Law Program and Privacy Official, Texas Legal Services Center
Location: Workshop Area
Over 49 million older Americans and people with disabilities receive Medicare health insurance. In July 2008, the Medicare Improvements for Patients and Providers Act (MIPPA) changed existing law (see: http://www.gpo.gov/fdsys/pkg/PLAW-110publ275/pdf/PLAW-110publ275.pdf ). Those changes fund (1) the promotion of prevention and wellness benefits, (2) Part D counseling in rural areas, and (3) Medicare Part D Extra Help/Low-Income Subsidy (LIS) and Medicare Savings Programs (MSPs) application assistance. Beneficiaries in fair/poor health without supplemental insurance incur average annual out-of-pocket costs of $4,500. Since 2009, MIPPA-funding has helped tamp down those costs for society's most vulnerable members, accessing more than $2.3 billion in benefits by grantees submitting more than 860,000 applications. This workshop will cover a history of MIPPA's development, including the recent Developments through the Medicare Access and CHIP Reauthorization Act of 2015. It will review benefits available under MIPAA, discuss some success stories and best practices, and will outline additional room for improvement, should Congress be listening. Learn more at www.tlsc.org.
3:45pm – 4:45pm
Accessibility Features of Smartphones and Tablets
Presented by Ben Lippincott, Project Director, Rehabilitation Engineering Research Center for Wireless Technologies; and Kendra Cox, Compliance & Outreach Manager, Corporate Accessibility Technology Office, AT&T
Location: Workshop Area
The workshop explores the many accessibility features found on today's most current smartphones and tablets. Uncover features that are helpful for people who use hearing aids, use text and video services, have communication difficulties, have difficulty seeing, have dexterity or mobility impairments, or have attention, concentration or sensory difficulties. Caregivers and professionals will also benefit by understanding these features as they assist people with disabilities. This workshop will focus on the latest Apple (iOS8) and Android (5.0) Operating Systems, as well as previous systems. Attendees will also discover resources for services, devices and mobile applications. This workshop is part of the "Wireless Independence Now!" workshop series presented by AT&T and Wireless RERC. Learn more at www.wirelessrerc.org.
Saturday, August 1, 2015
11:45am – 12:45pm
How to Select the Right Accessible Vehicle for You
Presented by BraunAbility
Does the process of purchasing adaptive equipment for a vehicle leave you feeling challenged and frustrated? Consumers and related healthcare professionals alike are invited to join us to learn the tips to successfully navigating the purchase of vans and accessible modifications. This workshop will cover such topics as what solutions are available and where to find them, key terminology, the shopping and evaluation process, funding options and much more. Following the session attendees are invited for a hands-on van demo at BraunAbility's Booth #103. Learn more at www.nmeda.com.
1:00pm – 2:00pm
Access the World: Tips for Traveling with a Disability
Presented by Debra Kerper, Easy Access Travel
Location: Workshop Area
Would you like to travel the country or the world, but believe you cannot because of your disability? At this workshop you will learn that travel by air, sea and car is a real option for you. The presenter, a professional travel agent who has a disability and has travelled extensively, will share with you how to plan a trip, including what to expect form hotels, rental car companies, cruise lines and the airlines. Learn about the common challenges, methods for addressing them and what the law requires. Attendees will receive recommendations for disability-friendly destinations and accessible travel resources. Be sure to bring your pressing questions and a list of places you'd like to visit. Learn more at www.easyaccesstravel.com.
2:30pm – 3:30pm
Medical Marijuana: Benefits and Legalization
Felicia Carbajal and Andrew Kuebbing, Co-Founders, California Cannabis Advocates
The last decade has brought incredible progress to the science of cannabis medicine. There are now a myriad of options besides inhalation for almost any condition, including dosed liquid extracts, edible oils, medicated foodstuffs, patches, tablets, lozenges, and more! Discover what research is telling us about the positive medicinal impacts of therapeutic cannabis for people on the Autism spectrum and with other types of disabilities, including spinal cord injury (SCI), multiple sclerosis (MS) and more. With the advent of inexpensive potency testing for cannabis, you can now be confident of your dosing, as well as titrating the amounts of THC and CBD and changing your ratio (for pain vs inflammation). Also learn how to use cannabis topically with salves, balms, and creams. Learn more at www.californiacannabisadvocates.com and www.facebook.com/CACannAdvs.
3:45pm – 4:45pm
Questions and Answers with Dr. Andrew Wakefield
Location: Workshop Area
The Autism epidemic continues to increase in size with the latest estimates showing that 1 in 58 American children will develop Autism. The search for the causes and solutions is complex. Dr. Andrew Wakefield will be available to take your questions, discuss the possible environmental causes for autism and share information about real help and support available for people with Autism Spectrum Disorders and their families. Dr. Wakefield is the co-founder of the Autism Media Channel, a TV and video production company that seeks to bring awareness and hope to those interested in childhood developmental disorders.
Announcement: We regret that due to an unexpected schedule conflict Dr. Wakefield is not available to present at Abilities Expo Houston this year. Fortunately, staff from Autism is Medical will present in his place and will be able to answer questions you planned to ask Dr. Wakefield. To learn more about AIM visit www.autismismedical.com.
Sunday, August 2, 2015
Caregiver Day at Abilities Expo
The following workshops are presented by the Christopher and Dana Reeve Foundation and are geared for the loved ones who give so much.
11:45am – 12:45pm
Coaching for Caregivers: How to Reach Out Before You Burn Out
Presented by Yosaif August ACC
Location: Workshop Area
This presentation will outline the concepts around reaching in, reaching out and provide practical tools and resources for caregivers.
1:00pm – 2:00pm
Meditation and Yoga Capsules Seminar
Presented by Jay Gupta RPh, MScIM, MTM, RxYT and Terry Gupta MSW, RxYT, RMT
Location: Workshop Area
This workshop will demonstrate several key concepts around meditation and yoga that will help caregivers rejuvenate their mind and body. No special clothing or flexibility level is required for this workshop.
2:30pm – 3:45pm
Care for the Caregiver: When You Can't Stop the Waves Learn How to Sail
Location: Workshop Area
Discover several concepts that will teach caregivers self-care practices around remaining healthy and resilient themselves as they assist a loved one with their caregiving needs.