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Published 07/06/2016
Beefeater-costumed doormen welcome you into the regal lobby of this 1928 landmark property, fresh off a $30-million face-lift, while guest quarters are fitted with typical technological amenities yet evoke the era with regal headboards atop beds draped in blue, white, red, and gray. The renovation was just what this place needed, injecting it with new life and energy, and the cumulative effect is of an Italian castle restored to her former glory, with a lobby decked out with chandeliers, Italian marble, velvet furnishings, and a centerpiece bar hugged by silver stools and a pair of Renaissance-inspired murals. Something that hasn't changed is the first-rate location and rich history. Harry Denton's Starlight Room, on the hotel's top floor, is a tribute to faded 1920s glory and is one of the city's best-known skyline bars. Scala's Bistro serves better-than-average food in its somewhat noisy bi-level dining room.
450 Powell St., San Francisco, California, 94102, United States
415-392–7755; 800-795–7129
Website: www.sirfrancisdrake.com
Hotel Details:
Published 07/06/2016

subset: commoncrawl


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© Copyright 2017 The girl in the red scarf. All rights reserved.
Status: Finished
Genre: Fantasy
A sad poem from within. I like the manner in which you expressed your feelings but do not lose hope. When the dark clouds moved away, you will see the blue sky.
Very nice poem, quite complex but flows well.
Please read my latest poem, The Pivot if you have time,...cheers!!
thank you very much.
i needed an appreciation for my first poem on this site
oh ma gurl...
straight from your heart....
remember..no matter what happens..things will never end in a bad manner..
though u r bearing so much of pain and stuff...but trust me the end we all will be happy..that is for sure...
gurl...learn it like u did.. ABCD...."LIFE IS NOT BAD AT ALL!"
whats with...."SEARCH OF FAME"???
now all u gotta do ,, really,, is just smile...
that is the only way!
trust me..
i have been through exactly the same one...more worse!
this is the only way out!
just let go....
and one more last thing...
all you do is never like" DO GOOD AND CAST IT INTO THE RIVER!"
if you are not gifted the result of your hard work immediately..
it doesnt mean you'll never be getting it!
just wait my dear...
wwell ma comment is pretty big one...not ma' fault....your poem is just like that so true....so much heartfelt....
lots of blessings hunie....
this is a lovely poem straight from the heart, keep up the good work :D
I like this poem. It is deep and sad, moving and profound.
The feelings of the soul written by the heart.
Poem / Fantasy
Poem / Other
Poem / Other
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Spayed female, 3 years old, Terrier Mix, 40 pounds
Annie was dropped off at a local shelter with her 6 puppies when they were only a month old. The little family had been abandoned in a backyard when the property owner was put in jail, and neighbors had been trying to keep them fed. Unfortunately, the owner never returned, and Annie and pups found themselves at the shelter.
Annie was heartworm positive, but went through fast-kill treatment on 11/16/16. She will be spending this month on cage rest. She is a young, vibrant, fun little gal that enjoys playing with toys and other dogs. She does not like cats, and will chase them. We are not sure that she has ever experienced life inside of a home. Our desire is to find an adopter that understands that Annie may need a little time to adjust to life as an "inside" pet. Annie's hope is to be in her own, warm home, by Christmas! Her adoption fee has been reduced to $200, which includes a 6 month supply of heartworm pills.
Annie has been spayed, microchipped, vaccinated, and is on her monthly preventatives. She is in foster care in East Tennessee. Her adoption fee is $200 which includes all vetting and transport. Vet references, personal references, and home visits may be required prior to adoption.
If you'd like to find out more information about our adoption procedure or to apply for this dog, please visit our link: http://poochesonthemove.net/paws-of-valor/. You may also e-mail us at firstname.lastname@example.com to request an adoption application. We look forward to talking to you soon!
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Your message has been sent to Pooches & Purrs Cooperative - Hagerstown.
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Congressman Ryan Zinke's nomination for Secretary of the Interior was approved by the U.S. Senate's Energy and Natural Resources Committee by a vote of 16-6. Zinke said he was an "unapologetic admirer of Teddy Roosevelt," in his confirmation hearing. Zinke is a lifelong hunter and outdoorsman. He's got a last-minute traditional ammunition ban from the previous administration's U.S. Fish and Wildlife Service director waiting for action. On the last full day in office, Director Dan Ashe published Director's Order 219, banning all traditional ammunition on U.S. federal lands in just five years. Zinke told the committee in his hearing that far-reaching decision such as these need to be made in consultation with state and local authorities, not edicts from Washington D.C. NSSF support for Zinke was entered into the Congressional record, but now he needs the vote of the majority of the Senate. Contact your Senator today to vote yes on Zinke.
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Updated bi-monthly, this report provides a snapshot of top-selling brands of firearms, optics and features market leaders for shotgun ammunition and balls, bullets or shot. Also includes insight into hunting license purchases. NSSF Business Members also have access to historical reports.
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Mawa And Almond Pudding Hot
|100 Gram (Or 1/2 Cup Hariali Variety)
|100 Milliliter (Or 1/2 Cup)
|Grated almonds/Grated cashewnuts
|40 Gram (Or 1/2 Cup)
|Almond essence
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1. Blend the mawa, milk, whole eggs, sugar and nuts in the blender for 5 minutes. Add essence.
2. Lightly caramelize a jelly mould and pour in the mixture.
3. Seal the mould with grease proof paper or aluminium foil. Place in water bath and bake in the oven for 45 minutes.
4. Garnish with slivered almonds.
Recipe Summary
Rate It
Nutrition Rank
Nutrition Facts
Serving size: Complete recipe
Calories 1230 Calories from Fat 533
% Daily Value*
Total Fat 60 g92.1%
Saturated Fat 23 g115.2%
Trans Fat 0 g
Cholesterol 530 mg176.7%
Sodium 551 mg23%
Total Carbohydrates 127 g42.5%
Dietary Fiber 4 g16%
Sugars 120.7 g
Protein 50 g100.2%
Vitamin A 30.1% Vitamin C 14.3%
Calcium 107.9% Iron 13%
*Based on a 2000 Calorie diet


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Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study
DOI: 10.1186/ar2315
© Krzeski et al.; licensee BioMed Central Ltd. 2007
Received: 25 June 2007
Accepted: 24 October 2007
Published: 24 October 2007
We performed a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study of the efficacy and safety of the oral administration of PG-116800, a matrix metalloproteinase (MMP) inhibitor, in patients with mild to moderate knee osteoarthritis. The primary efficacy endpoints included the progression of joint space narrowing in the osteoarthritic knee, as measured by microfocal radiography with fluoroscopic positioning, and the reduction of symptoms (pain and stiffness) and/or the improvement of function, as measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Four hundred and one patients were randomly assigned to either placebo (n = 80) or one of fourdoses of PG-116800: 25 mg (n = 81), 50 mg (n = 80), 100 mg (n = 80), or 200 mg (n = 80) taken twice daily for 12 months. During the study, the 200-mg dose was discontinued based on an increased frequency of musculoskeletal adverse effects. After 1 year of treatment, no statistically significant difference was observed between placebo and PG-116800 with regard to mean changes in minimum joint space width of the knee or to WOMAC scores. The most frequent adverse effect was arthralgia (35%). Twenty-three percent of evaluable patients had at least a 30% decrease from baseline of at least onerange-of-motion measurement of either shoulder at a follow-up visit. The percentage of patients with reduction in range of motion was significantly greater in the twohighest dose groups relative to placebo. Thirteen percent of patients, half of whom were in the 200-mg group, reported hand adverse events (oedema, palmar fibrosis, Dupuytren contracture, or persistent tendon thickness or nodules). The threemost frequent shoulder adverse events were reversible arthralgia, stiffness, and myalgia, which mostly affected the twohighest dose groups. The unfavorable risk-benefit balance of the MMP inhibitor PG-116800 in patients with knee osteoarthritis precludes further development of the compound for this indication. This study adds to the weight of evidence suggesting that side effect profiles of MMP inhibitors in general make them unsuitable for use in osteoarthritis.
Trial Registration
ClinicalTrials.gov NCT00041756.
Osteoarthritis (OA) is a chronic, progressive disorder of the synovial joints, characterized by focal loss of cartilage and changes in subchondral and marginal bone, synovium, and periarticular structures [1]. The disorder commonly affects weight-bearing joints and results in pain and loss of function [2]. Current therapies (analgesics and nonsteroidal anti-inflammatory drugs [NSAIDs]) are mostly symptomatic and include adjuvant interventions such as weight loss and physical therapy to improve physical function. As the understanding of the pathogenesis of joint destruction in OA increases, new therapeutic approaches are targeting the tissue degradation process.
Matrix metalloproteinases (MMPs) are a group of approximately 30 proteolytic enzymes, which collectively degrade all the components of the extracellular matrix during tissue formation and remodelling [3, 4]. As degradation of the extracellular matrix is essential for growth and progression of malignant tumors, MMP inhibitors have been extensively studied as potential anticancer agents [4]. MMPs have also long been implicated in the joint destruction process that occurs in arthritis, and MMP inhibitors have been studied in the treatment of both rheumatoid arthritis and OA [5–7]. Increased levels of MMP-1 and MMP-3 have been observed in the cartilage and synovium of patients with OA and have been correlated with the severity of the condition [8]. Animal models have shown that MMPs were good therapeutic targets [9]. Despite promising preclinical data [10–13], however, development of MMP inhibitors in arthritis seldom continued into humans, hampered by safety issues or an unfavorable efficacy profile in other indications [14]. To our knowledge, no controlled long-term studies with MMP inhibitors in OA have been performed to date.
In long-term trials in oncology, the use of MMP inhibitors has been associated with musculoskeletal toxicity, which was the primary reason for program termination for some compounds of this class [15, 16]. Signs and symptoms described in the literature generally consisted of musculoskeletal pain and inflammation, usually originating in the upper shoulder girdle or hands, and also arthralgia, myalgia, joint stiffness, limb pain, Dupuytren contracture, and/or peripheral pain and oedema [4, 17–23]. In published studies, musculoskeletal symptoms tended to occur after 2 to 3 months of treatment, to be dose-dependent, and to be generally reversible within 1 to 3 weeks of treatment discontinuation [4, 17–19, 23].
PG-116800 is a member of the hydroxyproline-based hydroxamic acid class of MMP inhibitors which has been shown to inhibit the joint damage caused by iodoacetate injection into rat knees, an experimental model for OA [24]. PG-116800 has high affinity for MMP-2, -3, -8, -9, -13, and -14, the therapeutic targets, while having substantially lower affinity for MMP-1 and -7, both of which were thought to be implicated in the pathogenesis of musculoskeletal toxicity [25].
This randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study was conducted to evaluate the relative efficacy of PG-116800 versus placebo in slowing the progression of joint space narrowing in knee OA (structural objective) and in reducing symptoms and/or improving function (symptomatic objective) over the course of 12 months and to assess the safety of its administration. The minimum joint space width (JSW) in the medial compartment of the tibiofemoral joint was measured from microfocal knee radiographs obtained by fluoroscopic positioning. Microfocal radiography was chosen for this study since investigators had shown that quantitative evaluation of measurements obtained from macroradiographs detected JSW changes within a shorter time frame than was possible using standard radiography [26, 27]. Here, we report one of the largest studies of MMP inhibitors and describe the adverse musculoskeletal effects of the drug.
Materials and methods
Design and patients
Men and postmenopausal and/or hysterectomized women, 40 to 80 years of age, with primary OA of the knee according to the American College of Rheumatology criteria [28] were eligible to participate in the study. For the purpose of the radiographic assessment, patients had to have at least one knee that could be designated a 'signal knee' on microfocal x-ray, as defined by at least oneosteophyte in either the medial or the lateral compartment of the tibiofemoral joint (tibial spine osteophytes could be included), a JSW in the medial tibiofemoral compartment greater than or equal to 2 mm and less than 4.5 mm in the semiflexed view, and a medial compartment JSW that was narrower than the lateral compartment JSW for the same knee. Exclusion criteria included secondary OA, nonosteoarthritic causes of knee pain, significant medical or psychiatric conditions, chronic shoulder disease, severe obesity, previous intra-articular injection of either knee or of any other joint with steroids, previous intra-articular injection of the signal knee with hyaluronic acid, diagnostic arthroscopy, use of systemic steroids or knee injury within 3 months of study entry, history of surgery or surgical arthroscopy of the signal knee, and recent therapy with a drug of the tetracycline class, with calcitonin, systemic fluoride, bisphosphonate, glucosamine, digoxin, warfarin, inhibitors, or inducers of cytochrome P450 3A4, 1,25 (OH)2 D3 or with more than 400 IU/day of vitamin D2 or D3.
The study was conducted in 16 centers in the UK and 8 centers in Hungary between July 2002 and February 2004 in compliance with International Conference on Harmonization guidelines, the US Code of Federal Regulations, European Community guidelines, and the Declaration of Helsinki. Each study site's ethics committee approved the protocol, and all patients provided written informed consent. An Independent Data Monitoring Committee (IDMC) monitored unblinded data for safety.
Treatments administered
Eligible patients were randomly assigned to receive orally twice daily for 1 year onecapsule containing either placebo or one of fourdoses of PG-116800 (25, 50, 100, or 200 mg). The PG-116800 capsules were supplied by Procter & Gamble Pharmaceuticals (Mason, OH, USA) as white opaque gelatin shells containing PG-530742 (the dihydrated sodium salt PG-116800), lactose monohydrate (National Formulary, NF), and magnesium stearate NF. Placebo capsules were identical in composition and appearance to the capsules containing active drug but did not contain drug substance. During the in-life portion of the study (November 2003), the IDMC recommended discontinuing the 200-mg dose based on an increased frequency of musculoskeletal adverse effects.
Outcome and safety assessments
The progression of joint space narrowing in the osteoarthritic knee (structural primary endpoint) was evaluated by measuring the 1-year change from baseline in minimum JSW in the medial compartment of the tibiofemoral joint of the signal knee, using microfocal knee radiographs obtained in the semiflexed position. To ensure proper alignment of the tibial plateau and centering of the tibial spines relative to the femoral notch, fluoroscopic positioning was performed before the radiograph was acquired. Study radiographers in twocenters (one in Hungary and one in the UK) performing microfocal x-ray underwent specific training and testing before participating in the study. The reduction of symptoms and/or improvement of function of the knee (symptomatic primary endpoint) was measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) total score (version3.1) at 1 year [29]. Secondary endpoints included the consumption of analgesics and NSAIDs as pain medication for OA and the Patient Global Assessment ('Considering all the ways your OA affects you, how have you been in the last 48 hours?').
Tolerability and safety were evaluated at each visit through interviews by the site personnel. All treatment-emergent adverse events were recorded, and their severity (mild, moderate, or severe) and relationship to the study drug (doubtful, possible, or probable) were graded by the investigator. Clinical laboratory tests, electrocardiograms, and chest radiographs were performed regularly.
The occurrence of musculoskeletal effects was carefully monitored because of musculoskeletal toxicity reported with other MMP inhibitors in oncology trials [17]. Based on a literature review, a working definition of the MMP inhibitor-associated musculoskeletal syndrome (MSS) was developed and included painless loss of range of motion (ROM) in large joints (particularly in the shoulders), joint stiffness and joint swelling, soft tissue pain, and fibrosis of palmar tendons (Dupuytren contracture). To assess potential musculoskeletal toxicity, each follow-up visit included serial measurements of shoulder ROM (anterior flexion, abduction, internal rotation, and external rotation) at the site by an appropriately trained person using a goniometer; examination of palmar tendons for evidence of palmar tendon fibrosis, tendinitis, fasciitis, or inflammation; and elicitation of MSS symptoms through questioning. A diagnosis of MSS was considered likely if a patient (a) developed palmar fibrosis, (b) lost at least 30% of any shoulder ROM, as measured by goniometer, or (c) presented with musculoskeletal signs or symptoms the investigator considered to be significant and consistent with those previously reported in the literature. No specific blood biomarker of MMP inhibitor-related musculoskeletal toxicity was identified and collected. Patients with signs and symptoms consistent with MSS could undergo ultrasound of the hands and shoulders at the investigators' discretion and the sponsor's recommendation. The IDMC reviewed unblinded study data quarterly to enable the early discontinuation of doses that appeared to be associated with any unacceptable adverse events, with particular attention to any evidence of MSS.
Sample size determination
The study was designed to detect a 50% reduction in JSW change at 1 year with 80% power, using one-sided comparisons, each made at an α value of 0.10 (not adjusted). The sample size of 75 patients per group (for a total of 375 enrolled) assumed a yearly loss in JSW of 0.2 mm, with a standard deviation of 0.25 mm. Treatment groups were sized to accommodate a 20% dropout rate. In addition, without regard for multiple outcomes, the study had 80% power to detect a 17% effect of treatment versus placebo with respect to pain modification, as measured by the pain subscale of the WOMAC index (assuming one-sided comparisons, each made at an α value of 0.10, a placebo mean of 160 mm, and a standard deviation of 70 mm).
Randomization method
Patients were randomly assigned to fivetreatment groups using an Interactive Voice Response System (IVRS). Randomization of patients was balanced according to their current use of estrogens or selective estrogen-receptor modulators (SERMs) in which twostrata were formed. An adaptative randomization technique [30] was employed to better achieve treatment balance within each site, each estrogen/SERM stratum, and across the entire study. The pooled study center was treated as a stratification factor for all applicable efficacy endpoint analyses. The treatment codes were controlled by the clinical supplies department of Procter & Gamble Pharmaceuticals.
This was a double-blind study with limited access to the randomization code. Study drug was dispensed according to the instructions provided via the IVRS. The treatment each patient received was not disclosed to study personnel, participants, contractors (except for clinical supplies distributor and IVRS contractors), or the sponsor (except for select clinical supplies, pharmacovigilance, bioanalytical, and pharmacokinetics personnel).
Statistical analysis
An intent-to-treat (ITT) analysis was conducted on all patients who were randomly assigned and took at least one dose of study drug. Any missing data for these patients were not imputed in the primary analyses. Thus, the efficacy analyses were based on the ITT patients with observed data at the time point under consideration. Paired t tests were used to test change from baseline values.
The 1-year change from baseline in minimum JSW in the medial compartment of the tibiofemoral joint of the signal knee was determined from the 12-month radiograph back to baseline. The significance of the 1-year change from baseline in minimum JSW and WOMAC total score was estimated using an analysis of variance. Minimum JSW change estimates were adjusted for baseline JSW, pooled center, and baseline use of estrogen or SERM drug replacement therapy as covariates. WOMAC change estimates were adjusted for baseline total scores, pooled center, and baseline use of estrogen or SERM drug replacement therapy as covariates. Each dose group was compared with the placebo control group. Each of these comparisons was made using a one-sided test with an α value of 0.10. Secondary endpoints were analyzed in a similar fashion.
Safety analyses included the ITT population. ROM measurements were analyzed and adjusted for pooled study centers as covariates. Comparisons between treatment groups were made to placebo for each visit. Additionally, the proportion of patients with detectable decreases in ROM was summarized. The proportion of patients with palmar tendon fibrosis, palmar tendon tendonitis, or palmar tendon fasciitis was summarized. Adverse events were tabulated and summarized according to the Medical Dictionary for Regulatory Activities (MedDRA). Percentages of patients reporting a decrease in shoulder ROM were compared to placebo by means of the Fisher exact test. Changes in joint symptom severity were tabulated and summarized, and percentages of patients reporting an increase in joint symptoms were compared to placebo by means of the Cochran-Mantel-Haenszel test after adjusting for pooled centers. P values for safety analyses were provided as flags for further investigation and were not adjusted for multiple testing.
Patient accountability
25 mg
50 mg
100 mg
200 mg
n (%)
n (%)
n (%)
n (%)
Patients randomly assigned
Patients who took at least onedose of study drug
Patients in per-protocol populationa
Patients completing 12 months of dosing
69 (90%)
65 (81%)
66 (84%)
64 (80%)
19 (24%)
283 (72%)
Patients who withdrew
8 (10%)
15 (19%)
13 (16%)
16 (20%)
60 (76%)
112 (28%)
Reason for withdrawal
Adverse event
4 (5%)
10 (13%)
6 (8%)
11 (14%)
34 (43%)
65 (16%)
Protocol violation
1 (1%)
1 (1%)
2 (3%)
2 (3%)
1 (1%)
7 (2%)
Voluntary withdrawal
3 (4%)
3 (4%)
4 (5%)
2 (3%)
3 (4%)
15 (4%)
Lost to follow-up
0 (0%)
1 (1%)
0 (0%)
1 (1%)
0 (0%)
2 (<1%)
Unable to meet protocol criteria
0 (0%)
0 (0%)
1 (1%)
0 (0%)
1 (1%)
2 (<1%)
IDMC recommendation
0 (0%)
0 (0%)
0 (0%)
0 (0%)
21 (27%)
21 (5%)
Demographic and baseline characteristics (intent-to-treat population)
25 mg
50 mg
100 mg
200 mg
(n = 77)
(n = 80)
(n = 79)
(n = 80)
(n = 79)
Age in years, mean (standard error of the mean)
62.0 (0.92)
62.4 (0.86)
62.6 (0.92)
62.9 (0.95)
63.1 (0.80)
Males, number (percentage)
23 (30%)
20 (25%)
18 (23%)
23 (29%)
30 (38%)
Females, number (percentage)
54 (70%)
60 (75%)
61 (77%)
57 (71%)
49 (62%)
Estrogen/SERM use among females, number (percentage)
5 (9%)
9 (15%)
6 (10%)
5 (9%)
4 (8%)
49 (91%)
51 (85%)
55 (90%)
52 (91%)
45 (92%)
Efficacy results
One-year change from baseline in joint space width of the signal knee (intent-to-treat population)
Treatment group
Joint space width at baseline
Joint space width at month 12
One-year change from baseline
Mean 1-year percentage change from baseline
P valueb (90% CI)
Mean (SEM)
Mean (SEM)
Least square mean (SEM)
3.386 (0.085)
3.252 (0.096)
-0.136c (0.063)
25 mg
3.350 (0.094)
3.307 (0.105)
-0.044 (0.062)
0.127 (-0.012, ∞)
50 mg
3.346 (0.094)
3.123 (0.113)
-0.226c (0.065)
0.869 (-0.193, ∞)
100 mg
3.413 (0.094)
3.218 (0.129)
-0.200c (0.065)
0.789 (-0.166, ∞)
200 mg
3.466 (0.108)
3.278 (0.138)
-0.192c (0.072)
0.740 (-0.166, ∞)
One-year change from baseline in total WOMAC scores (intent-to-treat population)
Treatment group
WOMAC total score at baseline
WOMAC total score at month 12
One-year change from baseline
P valueb (90% CI)
Mean (SEM)
Mean (SEM)
Least square mean (SEM)
41.8 (2.16)
32.9 (2.78)
-9.1c (2.81)
25 mg
42.6 (2.90)
35.9 (3.21)
-6.7c (2.78)
0.746 (-∞, 7.0)
50 mg
49.1 (2.46)
37.1 (3.20)
-10.0c (2.88)
0.403 (-∞, 3.7)
100 mg
50.9 (2.66)
42.4 (3.10)
-5.8c (2.92)
0.823 (-∞, 8.0)
200 mg
47.2 (3.70)
36.5 (4.54)
-9.3c (3.96)
0.483 (-∞, 5.6)
25 mg versus placebo
50 mg versus placebo
100 mg versus placebo
200 mg versus placebo
Safety results
Summary of adverse events (intent-to-treat population)
25 mg
50 mg
100 mg
200 mg
(n = 77)
(n = 80)
(n = 79)
(n = 80)
(n = 79)
Patients with adverse events, number (percentage)
52 (68%)
51 (64%)
51 (65%)
62 (78%)
62 (78%)
Patients who withdrew, number (percentage)
8 (10%)
15 (19%)
13 (16%)
16 (20%)
60a (76%)
Patients with serious adverse events, number (percentage)
8 (10%)
7 (9%)
12 (15%)
10 (13%)
17 (22%)
Patients who died, number (percentage)
0 (0%)
0 (0%)
0 (0%)
1 (1%)
1 (1%)
Changes from baseline in shoulder range of motion (intent-to-treat population)
25 mg
50 mg
100 mg
200 mg
Patients with ≥30% decrease from baseline in ≥1 ROM measurement at any postbaseline visit for either shoulder, number (percentage)
12/77 (16%)
11/79 (14%)
18/78 (23%)
24/79 (30%)
25/78 (32%)
P valuea
Patients with ≥30% decrease from baseline in the same ROM measurement at 2 or more consecutive postbaseline visits for either shoulder, number (percentage)
4/74 (5%)
5/78 (6%)
8/74 (11%)
12/77 (16%)
11/73 (15%)
P valuea
Patients with ≥30% decrease from baseline in 2 or more ROM measurements at the same postbaseline visit for either shoulder, number (percentage)
2/77 (3%)
2/79 (3%)
5/78 (6%)
13/79 (16%)
12/78 (15%)
P valuea
Patients with hand adverse events (intent-to-treat population)
25 mg
50 mg
100 mg
200 mg
Patients with hand adverse events, number (percentage)
5/77 (6%)
8/80 (10%)
9/79 (11%)
7/80 (9%)
23/79 (29%)
Patients with particular hand findings (hand oedema overlapped with other findings), number
Hand oedema
Palmar fibrosis
Dupuytren contracture
Tendon thickness/nodules
Symptomatic patients, number
The threemost frequent shoulder adverse events were arthralgia, stiffness, and myalgia. The first cases of shoulder arthralgia, which affected either shoulder with similar frequency, appeared after 1 month of dosing. Over the course of the whole study, 13%, 16%, 13%, 21%, and 25% of patients, respectively, in the placebo, 25-mg, 50-mg, 100-mg, and 200-mg dose groups reported shoulder arthralgia. Shoulder stiffness, which was usually isolated but sometimes accompanied by stiffness in other joints, was reported starting at month6. Over the course of the study, 1%, 4%, 6%, 9%, and 6% of patients, respectively, in the placebo, 25-mg, 50-mg, 100-mg, and 200-mg groups reported shoulder stiffness. Shoulder myalgia generally affected the deltoid muscle and was reported in 1%, 1%, 4%, 3%, and 6% of patients, respectively, in the placebo, 25-mg, 50-mg, 100-mg, and 200-mg groups over the course of the study. The threemost frequently reported shoulder adverse events could represent different reporting of a similar symptomatology. An analysis combining the threemost frequent shoulder adverse events showed a dose-related response starting after 3 months of dosing, continuing through months6 and 9, and disappearing at month 12 (data not shown).
Other symptoms included neck pain (3%, 4%, 4%, 6%, and 10% of patients, respectively, in the placebo, 25-mg, 50-mg, 100-mg, and 200-mg groups), which could be due to referred pain originating in the shoulder, and shoulder periarthritis (1%, 3%, 1%, 4%, and 6% of patients, respectively, in the placebo, 25-mg, 50-mg, 100-mg, and 200-mg groups). Shoulder ultrasounds were performed at the investigator's discretion in some symptomatic patients. Of 13 symptomatic patients in whom rotator cuff rupture (partial or complete tear) was found on shoulder ultrasound during the study, 3 patients each were in the placebo, 50-mg, 100-mg, and 200-mg groups and 1 patient was in the 25-mg group. Few patients (7%) had a combination of shoulder and hand symptoms that appeared independent of each other.
Follow-up data after PG-116800 withdrawal in patients with clinically significant shoulder findings and hand adverse events
Level of recovery
Number of patients
Mean time (days)
Median time (days)
Minimum time (days)
Maximum time (days)
Additional 3 patients recovered while still on drug
Additional 3 patients recovered while still on drug
Unchanged vs. baseline
Unchanged vs. baseline
Additional 1 patient recovered while still on drug
Unchanged vs. baseline
This proof-of-concept and dose-ranging study failed to demonstrate efficacy of PG-116800, an MMP inhibitor, in modifying the course of knee OA in patients with mild to moderate disease during a 12-month treatment period, as determined by microfocal x-ray assessment of JSW and analysis of WOMAC total scores, despite promising results of nonclinical studies [9, 10, 12].
The study confirmed that microfocal radiography is a sensitive tool in detecting a decrease in JSW in osteoarthritic patients over the course of a 12-month period. The progression of OA as evidenced by a decreasing JSW coexisted with symptomatic improvement from baseline in all treatment groups, including placebo. Significant symptomatic placebo response has been observed in OA studies of both intra-articular and oral medications and was noted in other recent studies [31–34]. This study seems to confirm that patients are likely to improve symptomatically and that the placebo effect persists for at least 12 months. Progression of JSW narrowing accompanied by symptomatic improvement over the course of a 1-year time period calls for further research in surrogate markers of OA activity and progression.
Although the majority of the cases described in the literature have been associated with the use of marimastat in patients with cancer, musculoskeletal toxicity has been reported in association with most, if not all, other MMP inhibitors. Musculoskeletal effects have been observed in preclinical studies with other MMP inhibitors [35]. In preclinical studies conducted with PG-116800, swelling was observed around the joints of both rats and dogs during chronic toxicology studies (3 and 6 months in rats and 12 months in dogs;, Procter & Gamble Pharmaceuticals, unpublished data). In apparent relation to the swelling, rats and dogs had accumulation of collagen associated with the joint structures. In dogs, after 12 months of study, proliferation of periosteal fibrous tissue and resorption of bone were observed in the joint. The effects appeared to be reversible when observed at the end of a 3-month recovery period.
Because the potential musculoskeletal toxicity of MMP inhibitors was recognized before the study start, safety measures included shoulder ROM assessment and monitoring with an IDMC. Although a detailed hand examination was part of the baseline physical examination, investigators were sensitized to hand findings after cases of asymptomatic nodules were observed. IDMC-driven withdrawal of patients in the 200-mg dose group could result in cases of musculoskeletal toxicity being over-reported at withdrawal in this group following the unblinding. The hand findings had a striking clinical resemblance to those of early development of Dupuytren contracture.
One of the major challenges in identifying patients with drug-related musculoskeletal toxicity in the study population was the need to differentiate from the symptoms and signs of OA itself. Although upper girdle involvement in OA is less frequent than involvement of hips and knees, it is not uncommon for the two to coexist in the same patient. Additionally, in published series, up to 50% of asymptomatic patients more than 60 years of age had partial or full rotator cuff tears in shoulder imaging studies [36]. Since shoulder ultrasound was not part of the screening process in this study but was used for further workup in some patients reporting shoulder symptoms, the finding of a rotator cuff tear was not helpful in differentiating drug toxicity from age-related tissue degeneration.
The occurrence of the most frequently reported shoulder adverse events (arthralgia, myalgia, and joint stiffness) followed a time- and dose-response pattern. This pattern disappeared after 12 months. Early termination of the study by patients in the highest dose group as per the IDMC recommendation after most of the patients had been dosed for 6 months offers a plausible explanation together with early withdrawals of symptomatic patients.
A number of theories to explain the occurrence of the musculoskeletal effects observed with MMP inhibitors have been offered, but none of them has definitive proof to support it. Inhibition of sheddase activity attributed to hydroxamate-based MMP inhibitors might be responsible for musculoskeletal symptoms [4]. Sheddase activity converts membrane-bound cytokines and receptors to inactive forms. Therefore, inhibiting this conversion could result in inflammation. In support of this theory, patients treated with BMS-275291 (which has reduced activity against sheddases) initially did not experience MSS [4]. This finding was verified after longer treatment duration when similar adverse events were reported. Another theory was that musculoskeletal toxicity might be caused by MMP-1 inhibition [4]. In an attempt to minimize these effects, Bayer Corp. (West Haven, CT, USA) and Agouron Pharmaceuticals Inc. (La Jolla, CA, USA) developed tanomastat and prinomastat, which strongly inhibit MMP-2 and -9 and weakly inhibit MMP-1, -7, and -11. However, prinomastat continued to exhibit musculoskeletal toxicity, whereas tanomastat was abandoned for lack of efficacy in oncology indications [4, 37].
The study did not demonstrate efficacy of PG-116800, an MMP inhibitor, in the treatment of patients with knee OA. It indicated that musculoskeletal side effects compromise the safety of long-term (greater than 3 months) systemic administration of the compound. Shoulders were affected clinically, with a decrease in ROM and an increase in pain largely reversible upon drug discontinuation. A dose- and time-related focal accumulation of tissue consistent with palmar tendon fibrosis was observed after 2 to 3 months of treatment. These musculoskeletal side effects were similar to those reported for other MMP inhibitors. This is likely to reflect a class effect, as these adverse effects are now reported for most of the MMP inhibitors, and this further suggests that these agents are unlikely to be of practical clinical use for the treatment of OA.
= Independent Data Monitoring Committee
= intent-to-treat
= Interactive Voice Response System
= joint space width
- MedDRA:
= Medical Dictionary for Regulatory Activities
= matrix metalloproteinase
= musculoskeletal syndrome
= National Formulary
= nonsteroidal anti-inflammatory drug
= osteoarthritis
= range of motion
= selective estrogen-receptor modulator
= Western Ontario and McMaster Universities osteoarthritis index.
The authors thank Alain Moufarege for his contribution to the design and execution of the study, Carol Tonkin and Karen Maunder for their contributions to the setting up of microfocal radiography units and radiographic assessments, Wajanat Jan for performing ultrasound examinations and assisting in the interpretation of findings, and Pal N Kaposi for his contributions to the setting up of microfocal radiography units and radiographic assessments and for performing ultrasound examinations and assisting in the interpretation of findings. This study was funded by Procter & Gamble Pharmaceuticals. Isabelle Darnis-Wilhelm prepared the manuscript and provided editorial assistance on behalf of Procter & Gamble Pharmaceuticals.
Investigators involved in the study were as follows: Hungary: Geza Bálint, Budapest; Katalin Bors, Gizella telep; Dezso Dávid, Petöfi; Gyula Poór, Budapest; Laszlo Hodinka, Budapest; Ferenc Szanyó, Györ; Miklos Szendröi, Budapest; Laszlo Tamási, Miskolc; UK: David Doyle, London; Ken Evans, Tonbridge; Ian Farmer, Ashford; Jean Fraser, Awpley Bridge; Peter Harvey, Addlestone; Neil Jackson, East Crowley; Ronald Jubb, Birmingham; Richard Keen, Stanmore; Phil Marazzi, East Horsley; Mansur Salman, Edgbaston; James Scrivens, Stratford-upon-Avon; Tim Spector, London; HelenYates, Tunbridge Wells.
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- Pocock SJ, Simon R: Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975, 31: 103-115. 10.2307/2529712.View ArticlePubMedGoogle Scholar
- Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO, Weisman MH, Jackson CG, et al: Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006, 354: 795-808. 10.1056/NEJMoa052771.View ArticlePubMedGoogle Scholar
- Ernst E: Glucosamine and chondroitin sulfate for knee osteoarthritis. N Engl J Med. 2006, 354: 2184-2185. 10.1056/NEJMc060829.View ArticlePubMedGoogle Scholar
- Altman RD, Moskowitz R: Intraarticular sodium hyaluronate (Hyalgan) in the treatment of patients with osteoarthritis of the knee: a randomized clinical trial. Hyalgan Study Group. J Rheumatol. 1998, 25: 2203-2212.PubMedGoogle Scholar
- Lehmann R, Brzosko M, Kopsa P, Nischik R, Kresisse A, Thurston H, Litschig S, Sloan VS: Efficacy and tolerability of lumiracoxib 100 mg once daily in knee osteoarthritis: a 13-week, randomized, double-blind study vs. placebo and celecoxib. Curr Med Res Opin. 2005, 21: 517-526. 10.1185/030079905X38196.View ArticlePubMedGoogle Scholar
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Groovy Sock by Violet Green
Welcome! You are browsing as a guestWould you like to see projects made from this pattern and much more? join Ravelry now What am I missing?
Groovy Sock
This pattern is available for £2.99 GBP
buy it now or visit pattern website
buy it now or visit pattern website
For more information, see: http://www.sockyarn.co.uk/shop/groovy-sock-knitting-...


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We aim to promote all alumni to stay in touch with one another through our activities. The EUCRAF alumni now consist of many successful individuals who have continued their regulatory affairs professional career in the pharma industry, while some have pursued professional careers in academic institutions and governmental organizations. Here you'll find some of EUCRAF past students' testimonials.
We plan to develop activities for our alumni to keep them connected and involved with EUCRAF. All alumni are welcome to contribute and cooperate on the activities, especially the workshop and conferences. As most of our alums are active on LinkedIn, please take a moment to join EUCRAF LinkedIn Group as well as to follow EUCRAF Company Page and EUCRAF Twitter account.
All EUCRAF alumni are entitled to get special conditions and discounts for the EUCRAF Annual Meeting, Coaching Events and Workshops
Should you have any queries or if you require further information on EUCRAF Alumni, please get in touch with Gabriele Dallmann.
Your EUCRAF team.


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NBA ASG Has Best Viewership Since '13 NASCAR Going Big On Social Media For Daytona Atlanta United Signs RSN Deal With Fox Sports ESPN Tops ComScores In Unusually Slow Month Sportsnet Has Its First 360 VR Game Telecast Social Studies: WNBA Dream's Dan Goldberger NBC Criticized For Airing Avalanche-Sabres Media Notes ESPN's "GameDay" Reaches Milestone Dan Dakich, Tom Izzo Downplay Spat
Upcoming Conferences and Events
Apr 19-20
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SBD/December 14, 2012/Media
Discovery Enters Into Negotiating Window To Buy 20% Stake In Eurosport
Published December 14, 2012
ENHANCES DISCOVERY'S STRATEGY: Zaslav said with the acquisition of Eurosport, Discovery will be the "largest programmer in Europe and we'll be the largest pay-TV global programmer outside the U.S." Zaslav: "It really enhances our overall strategy of taking our great content … and taking it around the world. This helps to supercharge that international story and reinforces the fact that as a global company, we're much stronger and geographically, we're much more stable and positioned for growth." He notes Eurosport is the "leader in sports all across Europe," and there is "no platform that even comes close." Zaslav: "In fact, there is no platform that's really multi-country. So Eurosport is a great brand in 59 countries but more importantly, they're in the sports business without paying a lot of money for sports. … The attraction for us is we're in all 59 of those countries with between six and eight channels of our own. In most of those markets, we're the No. 1 channel for men, and we have a top channel for women. When you put that together with Eurosport, we think that we have some more value to bring to advertisers and distributors" ("Squawk on the Street," CNBC, 12/14).


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Lap up the Dog's Brew
From Moondoggies to premiere beer destination
Chad Deal 5 p.m., Feb. 22
Learn the art of animal tracking, discover and identify tracks, scat, and evidence of critters and their lifestyles. MTRP tracking guide leads you on two-hour dirt-time adventure. Wear long pants. Meet in front of Visitor Center.
One Father Junípero Serra Trail, San Carlos, 92119
Get directions
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Orange and Lemon Snow Aspic
|Unflavored gelatin
|1 Tablespoon (1 envelope)
|1⁄2 Cup (8 tbs)
|1⁄8 Teaspoon
|Orange juice
|1 1⁄2 Cup (24 tbs)
|Lemon juice
|1⁄4 Cup (4 tbs)
|Egg whites
|2 , unbeaten
|1 , rind grated
|1 , rind grated
1) In a small saucepan, add in gelatine, salt and sugar. Pour in 1/2 cup of orange juice.
2) Cook the mixture over a low flame while stirring constantly, till the gelatine has dissolved completely.
3) Take the pan off the flame. Add in the rest of the orange juice and lemon juice. Chill the mixture till it resembles the consistency of an unbeaten egg white.
4) Next, add in the unbeaten egg whites, grated lemon and orange rinds into the chilled gelatine mixture.
5) Beat the mixture using an electric beater to work up a nice foam.
6) Transfer the mixture into individual small moulds or a glass dessert dish. Chill till the aspic becomes firm.
7) For garnish, add thawed berries over the dessert or pour custard sauce on top.
Recipe Summary
Rate It
Nutrition Rank
Nutrition Facts
Serving size
Calories 122 Calories from Fat 2
% Daily Value*
Total Fat 0.23 g0.35%
Saturated Fat 0.03 g0.14%
Trans Fat 0 g
Cholesterol 0 mg
Sodium 62.3 mg2.6%
Total Carbohydrates 28 g9.4%
Dietary Fiber 1.3 g5%
Sugars 24.6 g
Protein 4 g7.9%
Vitamin A 3.8% Vitamin C 91.7%
Calcium 2.7% Iron 1.4%
*Based on a 2000 Calorie diet


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With Instructables you can share what you make with the world, and tap into an ever-growing community of creative experts.
I love soldering with a torch. It's useful for all kinds of applications, and it's a great way to join metal that's too big for a soldering iron, ...
Tools: -Butane torch -Cigarette Lighter -Pliers -Wire Cutters -"Third Hand" Tool -Safety Glasses Consumables: -Copper Wire -Lead-Free solder -Butane
Fill the torch First, you need to fill the butane torch. Turn the torch upside down, take the bottle of butane, and line the end up with the ...
Light the Torch Turn the torch switch on, turn the gas up (if you're using a variable torch), and light the torch with the lighter. The thicker the ...
You've got a solder joint! Good job. Once you've got all your wire soldered together, and you know that you don't have anything else to add, you can ...
Clockwork Piston (Steampunk)by Ali Ali Oxen Free
How to Steampunk Decorate an Electrical Wall Plateby GeorgianBay Scott
Copper Steampunk Watchamacallitby Moose Art Design
Join 2 million + to receive instant DIY inspiration in your inbox.
© 2016 Autodesk, Inc.


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Report: Jets Have 'Some Interest' In Jay CutlerThe Bears are reportedly shopping Cutler and willing to take a seventh-round draft pick for him. However, his contract might preclude teams from making an offer.
Darrelle Revis Court Hearing Delayed Until March 15, Reports SayRevis is facing two counts of aggravated assault, along with charges of robbery, conspiracy to commit aggravated assault and terroristic threats, a misdemeanor.
Report: Jets Make Contract Offer To CB K'Waun WilliamsThe Jets are reportedly among four teams that have offered a contract to free agent cornerback K'Waun Williams.
Report: Revis' Lawyers Say Voice Heard On Aftermath Video Is Not Jets StarHours after a video surfaced on TMZ.com on Sunday showing the aftermath of the alleged altercation between Jets star cornerback Darrelle Revis and two men on the streets of Pittsburgh, the player's attorneys went on the offensive.
Keidel: It's Just Hard To Believe Revis Is Wrapped Up In This MessIf Joe Namath reveled in bombast, Darrelle Revis reveled in nobility and humility, which is why his recent arrest makes no sense.
Darrelle Revis Turns Himself In To Police In PittsburghThe Jets star is charged with two counts of aggravated assault, along with charges of robbery, conspiracy to commit aggravated assault and terroristic threats, a misdemeanor. aggravated assault and terroristic threats, a misdemeanor, after the incident Sunday.
Charges Filed Against Darrelle Revis After Pittsburgh Altercation; Lawyer Says Jets Star Was The VictimJets cornerback Darrelle Revis was charged with multiple criminal counts late Thursday, following an early-morning altercation this past weekend.
Jets Release Left Tackle Clady After Just 1 SeasonThe veteran offensive lineman was due $10 million next season, making his return to New York under that contract unlikely.
Report: Jets Unlikely To Pursue QB Jay CutlerThe Jets' new quarterbacks coach has strong ties to Jay Cutler, but don't expect Gang Green to pursue the Bears signal-caller.
Palladino: Jets' Best Choice For QB, Garoppolo, Will Never Get HereRegardless if the Jets use their No. 6 pick in the draft on a quarterback, they will still need to find a veteran somewhere to bridge the developmental gap.
Jets Take A Risk, Claim Twice-Suspended Pennel Off WaiversThe New York Jets have claimed defensive lineman Mike Pennel, who was suspended twice last season, off waivers from the Green Bay Packers.
Keidel: It Will Be Two Entirely Different Offseasons For Jets, GiantsConsidering both our NFL clubs reside in the same state, city, and building, you could not find two more different demeanors than you glean from the New York Jets and New York Giants.


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- description
DetailsImproving the look of dark circles under the eyes is one of the most demanded beauty secrets. With skin that's delicate, you need a gentle product that's shaded perfectly to correct the blue tones that so many women complain about. With a soft yellow shade, this under-eye brightener counteracts blue and leaves a brightened surface. This gel-like formula is virtually invisible to the naked eye, yet creates the illusion of flawless skin. It's lightweight, oil-free, and hydrating.
- how to use
How to use
Take a small amount of product on your ring finger, pat your fingers together, and apply underneath your eyes and in the inner and outer corners.
Instead of rubbing, which can be too harsh, gently pat the product into your skin.
- view ingredients
Ingredients: Water (Aqua), Dimethicone, Octyldodecyl Neopentanoate, Glycerin, PEG/PPG-18/18 Dimethicone, Butylene Glycol, Alcohol Denat, Aluminum Hydroxide, Stearic ACId, Glyceryl Polyacrylate, Acrylates Copolymer, Sodium Chloride, Caprylyl Glycol, Dextrin Palmitate, Palmitic Acid, Methyl Diisopropyl Propionamide, Ethyl Methane Carboxamide, Hydrolyzed Corn Starch, Disteardimonium Hectorite, Magnesium Ascorbyl Phosphate, Glycosphingolipids, Hordeum Vulgare Extract, Sea Salt, Nylon-12, Xanthan Gum, Lecithin, Sodium Hyaluronate, Triethoxycaprylylsilane, Methicone, Hexylene Glycol, Disodium EDTA, Phenoxyethanol. May Contain: Mica (CI 77019), Titanium Dioxide (CI 77891), Iron Oxides (CI 77491, CI 77492, CI 77499), Ultramarines (CI 77007), Chromium Oxide Greens (CI 77288), Chromium Hydroxide Greens (CI 77289). Made in USA.
- Reviews
Write Your Own Review


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While most people know that Italy is shaped like a boot, few realize that Sicily is shaped like an island. Explore the world with this Groupon.
Choose Between Two Options
- $20 for $40 worth of Italian cuisine
- $45 for $90 worth of Italian cuisine for parties of four or more
- Click to see the full menu
Before plying his trade in Christiano's kitchen, owner and chef Chris Chirum worked as a chef for three decades, and his expertise shows in the menu's bounty of simple yet elegant meals. Several steps above workaday plates of pasta and meatballs, the dishes at Christiano's exude a handmade, pastoral aesthetic, with plates decorated with locally caught, whole-baked fish, racks of lamb in rosemary sauce, and four-cheese tortellini dumplings simmering in garlic butter sauce. A live pianist occasionally serenades diners as they feast on flaky Emerald Coast grouper or tomato-basil-topped linguine, making nights only slightly less sophisticated than an emperor penguin in a top hat.
Customer Reviews
4942 US Hwy 98 W
Santa Rosa Beach, FL 32459
+18502672185Get Directions


text: AJ's on the Green may be outside of your area. Please enter your delivery address to check availability Do you need any... Napkins & Utensils Continue to Checkout AJ's on the Green Back to Menu Your order refresh AJ's on the Green Your Shopping Cart is empty edit Delivery Address Please enter delivery address edit Delivery Time N/A* Add someone to this order AJ's Classic Club Sandwich Daily's thick center-cut applewood smoked bacon, smoked turkey, tomato, and avocado on toasted bread. Served with bistro fries. Prepared On White Or Wheat Bread?Select one of the choices Prepare On White Bread Prepare On Wheat Bread x $13.95 Special Instructions: Label Item For: or Cancel


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In large bucket, combine salt, sugar, cider, orange juice, stock and peppercorns. Add turkey and then enough of the water so that the turkey is just covered - by about ¼ inch. Brine turkey in bucket, in refrigerator, overnight (18 to 24 hours).
When ready to roast, remove turkey, rinse well and pat dry. Season outside and inside of the turkey to taste with seasonings of your choice. Roast at 325 or 350 degrees, basing the roasting time on the size of the turkey.
Read and share your thoughts on this story.


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Airport transportation san Francisco
Airport shuttle service San Francisco
San Francisco Airport transportation offers pick up and drop services to your homes, offices, schools and hotels from the airport. Your office colleagues, your big family, classmates and private tour groups can avail of our San Francisco Airport Shuttle service. Airport transportation San Francisco is a reliable, comfortable, fast and inexpensive way to travel to and from the airport. Online reservation is available at any time whenever you need. For more information about airport transportation contact us.
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Call at 1-866-744-0944 today and let our reservation specialists customize a travel package to meet your needs.
San Francisco Airport Shuttle Bus aims at providing every client with the safest travel experience.
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San Jose Student 7th Grader Heads To National Spelling BeeA San Jose seventh grader is getting ready for the competition of his life, representing the Bay Area in the Scripps National Spelling Bee near Washington DC.
SJ Student Spells J-A-R-A-B-E To Win The 2016 CBS Bay Area Spelling BeeFrom second place, to winning the top spot this year. The winner of the CBS Bay Area Spelling Bee is a familiar face. Congratulations to Rutvik Gandhasri!
Gallery: 2016 CBS Bay Area Spelling Bee Contestants49 students assembled in the studios of KPIX in San Francisco on Saturday to compete in the 2016 CBS Bay Area Spelling Bee.
Spelling Bee C-h-e-e-r-s: Classmates Cheer On William Xu At Campbell Middle SchoolClassmates at Campbell Middle School cheered on William Xu before this weekend's CBS Bay Area Spelling Bee.
KPIX 5 Spelling Challenge: Wednesday EveningTest your spelling skills with Allen Martin and Elizabeth Cook as they take on William Xu from Campbell Middle School.
Monday's KPIX 5 Spelling Bee ChallengeMatch your spelling skills against KPIX 5 anchor Frank Mallicoat and local school champion Aniketh Yatam
Hours Of Study Lead To Spelling Bee BerthThe road to the 2016 CBS Bay Area Spelling Bee takes many twists and turns for the 50 youngsters who earn a spot in the field.
Spelling Bee Veterans Recall Their Competitive DaysYou couldn't blame either Anna Grimaldo or Eric Landreneau if their palms got a little sweaty as they worked as volunteers during the written round of the 2016 CBS Bay Area Spelling Bee.
Drake Clue Not Enough To Save Contestant At National Spelling BeeContestant Dev Jaiswal was asked to spell the word "bacchius," but needed it to be used in a sentence.
Two Bay Area Students End Competition At National Spelling BeeTen of the nation's most poised young spellers have made it to the finals of the 88th Scripps National Spelling Bee, but the Bay Area spellers were not among them.
Cupertino Boy Who Gained Fame On YouTube Will Represent State At National Geographic Spelling BeeAn 11-year-old Cupertino boy will be representing California in the 27th annual National Geographic Bee in Washington D.C. next week.
Video: 2015 CBS Bay Area Spelling Bee Regional Championship Broadcast (Complete)The CBS Bay Area Spelling Bee Regional Championship was held Saturday, March 21, at the KPIX studios in San Francisco. (Six videos contain the complete competition as broadcast live on KBCW-TV)


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The Hot ChickHD Closed Captioning
Tom Brady
Open iTunes to preview, buy, and download this movie.
About the Movie
The hilarious Rob Schneider has been a gigolo. He's been an animal. And now a curse will make him something he's never been before -- a woman! Jessica Spencer is the hottest, most popular girl in high school. But she gets a big dose of reality when she wakes up in the body of a 30-something-year-old lowlife male (Schneider) and quickly discovers that trading on your looks isn't so easy when you're a girl who constantly needs a shave. How in the world can Jessica convince her friends (Anna Faris, Scary Movie, Scary Movie 2; Matthew Lawrence, Mrs.. Doubtfire; Eric Christian Olsen, Not Another Teen Movie) it really is her? And how can she change herself back into a teenage girl? The Hot Chick is a wild and wacky gender-bending comedy everyone can enjoy -- no matter what sex you are.
Rotten Tomatoes Movie Reviews
- Reviews Counted: 83
- Fresh: 18
- Rotten: 65
- Average Rating: 3.8/10
Top Critics' Reviews
Rotten: A crude teen-oriented variation on a theme that the playwright Craig Lucas explored with infinitely more grace and eloquence in his Prelude to a Kiss.
Rotten: Enough to make any woman or gay man wish they could beam themselves to planet Zoltron.
Rotten: Call it tastelessness with a message -- a dubious combination, like, for sure. Still, Schneider pulls off the masquerade pretty well.
Rotten: The movie's devices are so feeble, I think it was written on a napkin in a Denny's the day before principal photography began.
Customer Reviews
Down-right hilarious.
One of my favorites. Definetly the best (if not only decent) Rob Schneider movie. Introducing Rachel McAdams. Overall an extremely funny movie.
this is the best movie in the world.
i've seen this movie over twenty times, my friends and i can literally say every line and we say them on a daily basis, in the halls at school, on the phone, in the car and just to random people. there is not one single bad thing about this movie and having it for only 10 dollars to be with me wherever i go is a dream come true. itunes is currently mans greatest invention. peace&love. carolyn
Finally, iTunes has movies. But not much yet. Any way. LOL. This movie is hilarious and I can watch it over and over again. It cracks me up every time.
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- $17.99
- Genre: Comedy
- Released: 2002
- © 2002 Touchstone Pictures, All Rights Reserved


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Ceramic & Metal Touch Lamp
Floor Lamp with Shelves
Set/14 Pan Protectors
White Storage/Craft Cart
Set/2 Double-Walled Glasses
Electric or Cordless Snow Shovel
Mini Stepper
Magic Tracks™
Gravy Boat & Warmer
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very good
Very useful tour. My travel guide, Petr, was very knowledgeable. I said 'my' because only participant was me, tour wasn't cancelled although I was the only participant :)
MUSTAFA ERAY from Denizli, Turkey
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Pick-up serviceHotel details required
In front of Czech National Bank - Guide will be holding paper with "Spectrum tours" written on it. (Open in Google Maps)
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Product ID: 70713


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text:
Chick and Bill, I've been following your
discussion with sharp interest. You see, I've been keeping an eye on
a green center/gold edged 'Piedmont Gold' sport since '92.
Is it similar to 'Satisfaction' and 'Tyler's Treasure'? Yep.
But is it identical? Beats me. And it's totally
impractical to purchase each to grow side by side for another 8-10 years
to find out. From what Bill is saying, if I name, register and
market it, I'm simply trying to pull the wool over the public's eye by
trying to convince them this is something "new"...a thought that could
easily be found offensive. (Bill, I'm not picking on you or your
thoughts, I just don't know how you can second guess the intentions behind
my actions) Are you suggesting I toss the plant onto the compost
pile? Sorry, I don't see that happening. Or are you suggesting
I name it 'Satisfaction' or 'Tyler's Treasure' without being absolutely
certain it's identical? To do that would be rather unethical and has
the potential of only adding more confusion down the road. But if so,
which would I name it? Perhaps I could name a third of them
'Satisfaction', another third 'Tyler's Treasure', and the last third
'Tyler's Satisfaction'. Naa, there would be no treasure to find
satisfaction with in that option (baaad). Instead, I think
I'll come up with my own name, register it, and yes, then maybe even
market it...and hope no one thinks I'm trying to pull a fast one.