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#1 Ranked Children's Hospital by U.S. News & World Report
MyPatients provides referring primary care providers with secure access to their patients' information.
Boston Children's has launched the world's 1st program dedicated to offering hand transplants to children who qualify.
Innovation insider is a semi-monthly e-newsletter analyzes innovations at Boston Children's, other academic medical centers and from industry.
Read the latest blog by a Boston Children's doctor, clinician or staff member.
There are many ways you can help children and their families get the care they need.
Learn more about our ranking as the top pediatric hospital here.
The Department of Psychiatry at Boston Children's Hospital is a global leader in addressing the mental, emotional and biological aspects of brain disorders. Our commitment to evidence-based medicine—treatment regimens that have been proven effective through scientific research—and our belief that every child should be treated as an individual, not solely a recipient of treatment, make a lasting difference for patients and families in our care.
For more than 35 years, Boston Children's Neuropsychology Program has worked with children and families affected by brain and central nervous system disorders, injuries and diseases. Our clinicians have a wealth of expertise applying their understanding of brain-behavior relationships and development to help children and adolescents think, function and learn.
Boston Children's Hospital is home to one of the world's most accomplished pediatric psychiatry programs. Our Neuropsychology Program helps patients cope with problems of learning, memory, organization and emotional control resulting from brain injuries or neurological disorders.
If your child is living with brain or central nervous system damage or dysfunction, our expert clinicians can help evaluate her symptoms, connect you with other specialists throughout the hospital and work with you—and your child—to devise an effective treatment plan that takes all of your family's needs into consideration.
Boston Children's Neuropsychology Program team will work to assess your child's:
In addition, we will help you and your family:
By partnering with your family as key members of our treatment team, we can make a comprehensive assessment of your child's individual situation and provide critical tools to help your child lead a happy and fulfilling home, school and social life.
In the Neuropsychology Program at Boston Children's, clinical assessment is approached from a neurodevelopmental systems perspective which addresses:
Our assessment strategy emphasizes the close relationship among:
We believe in treating the "whole child," by addressing not only the cognitive symptoms of your child's illness, but also the emotional, educational and social needs of your entire family.
We are grateful to have been ranked #1 on U.S. News & World Report's list of the best children's hospitals in the nation for the third year in a row, an honor we could not have achieved without the patients and families who inspire us to do our very best for them. Thanks to you, Boston Children's is a place where we can write the greatest children's stories ever told."


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Star Tribune names CRMC a Top Workplace for the second year in a row
Cuyuna Regional Medical Center (CRMC) has been named a Top Workplace based on an employee-based survey project from the Star Tribune for the second year in a row. Top Workplaces recognizes the most progressive companies in Minnesota based on national standards of employee opinions about company leadership, communication, career opportunities, workplace environment, managerial skills, pay and benefits. The analysis included responses from over 64,300 employees of Minnesota public, private and nonprofit organizations.
The results of the Star Tribune Top Workplaces are based on survey information collected by WorkplaceDynamics, an independent company specializing in employee engagement and retention.
CRMC employs more than 900 physicians, nurses, health care professionals and support staff. "We are tremendously pleased to receive this honor for the second year in a row and are humbled by the feedback we received from our staff," said John Solheim, CEO of CRMC. "CRMC is an outstanding place and it is all because of the people who come here every day to care for our patients with the most dedicated, compassionate level of care."Star Tribune Publisher Michael J. Klingensmith said, "The companies in the Star Tribune Top Workplaces deserve high praise for creating the very best work environments in the state of Minnesota. My congratulations to each of these exceptional companies."
To qualify for the Star Tribune Top Workplaces, a company must have more than 50 employees in Minnesota. Nearly 1,900 companies were invited to participate. Results were calculated purely on the basis of employee responses. The full Star Tribune report can also be found at StarTribune.com/topworkplaces2012.
For almost 50 years CRMC has provided healthcare services to the Cuyuna and Brainerd Lakes region of Minnesota. The campus is home to primary care and specialty physicians with expertise in family medicine, internal medicine, general surgery, orthopaedics, obstetrics/gynecology, anesthesiology and emergency medicine. CRMC partners with specialists in the fields of cardiology, oncology, ophthalmology, sleep medicine and urology, and the medical facility also includes one of Minnesota's top institutes for minimally invasive surgery. Renowned medical expertise combined with on-site radiology, laboratory, pharmacy, and rehabilitation services make Cuyuna Regional Medical Center a comprehensive rural healthcare provider.

subset: commoncrawl


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[quote user="BlueSanta"][quote user="nycsportzfan"]I never did my weekly mock after the JET WIN Here we go! Picking 23rd is what i got us
1 Devon Still DT Penn St- Dudes a beast with a non stop motor and great size With Canty getting older and Austin being outta football for 2yrs by the time next season rolls around i think its a good idea taking Still here for his Upside and for the fact we need one more reliable big upside DT for the rotation going forward Still has 17TFL and 4 and a Half Sacks so far
2 Travis Lewis LB Oklahoma- I love Lewis! I think hes gonna be a huge steal if he goes this late in the 2nd round Hes a ALL AROUND LB who makes plays against the run and in the pass game I see a pro bowl in his future
3 Julian miller DE W Virginia- Another player i love! Julian reminds me of a young Justin Tuck for his size and Versatility as he lines up inside at DT for the WV club as well JPP and Julian would be a fearsome DUO at End going forward Julian has 11 TFL and 6sacks to go along with 2 FF so far this yr
4 William Vlachos C Alabama- A nasty mauling C whos been blocking for 2 rugged smash mouth runners in his time at Bama(ingram and richardson) and we could use a upgrade at C and possible long term answer
5 Tashaun Gipson CB Wyoming- A nice Depth CB who really helps in Run support and has solid size/speed combonation
6 Bobby Rainey RB W Kentucky- This kid flat out was W Kent's offense and a bruising workhorse ! A nice kid to take a chance on in RD 6 At worst could be a nice change of pace back and at best u strike lighting in a bottle again(bradshaw being other)
7 Evan Rodriguez TE Temple- Good hands and Solid size Blocked for a great RB DUO at temple while also being one of there bigger threats through the Air albeit they don't air it out at temple Evan has a chance
Heh I love Still, but he seems to me to be gone before we pick? He would be a perfect fit for us because I dont know if anyone gets more up-the-middle push than he does. I would feel bad for poor QBs who had to step up into the pocket because of Tuck, JPP, Osi only to find Still in your face. The big difference between the now Giants and the 2007 Giants is we dont have that Fred Robbins pocket crumbler. Still will blow up any pocket.
I know we have talked about Lewis. I would love him here. Giants like versatility in LBs. OKlahoma demands the same from its LBs. He is a good player.
All the other picks are good, though I am not in love with some of them as you are. But I wouldnt mind em either. I still think we need to take the TE position more seriously than a 7th rounder. At the very least, we need depth.
[/quote] I don't know if STILL will be there when we pick? He could be or then again he could be gone I remember we all thought Dan Williams was gonna be gone alot earlier then he went and i think he went pick 23 if i am not mistaken? I think its a toss up right now as to if he still there where i got us pickcing which is pick 23
I thought Linval was gonna get more push then he has and thats one of the reasons he was one of my fave prospects when he came out and why i wanted him so badly! Your totally correct as what were missing from our 2007 club Linval and Still would be a beastly duo! Especially if it becomes a Trio and Austin plays well!
Im not nessecarily in love with all the picks at the end of the mock its just the way this paticular one worked out We got plenty of positons that are in need of Depth or legit talent but only so many picks U gotta try and fill a few and find a couple diamonds in the ruff later on


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Good signs for Ford. Regularly exceeding real world EPA after people learn how to drive the CMax is the next obstacle needed to overcome in order for the CMax to earn street cred similar to Toyota. The CMax and Ford have a LONG way to go if they want to surpass total Prius sales.
Eh. Not a fan of this thing. I need to drive one to be sure, though.
looks better, preforms better, not really a surprise XD
--------------------I'm working on a scifi-adventure webcomic!
I've driven numerous hybrids over the years through work and friends.The Toyotas (every generation of Prius) were all terrible. Floaty suspension that rivaled the boat like Buicks my grandpa drove when I was a kid, cheap feeling interiors and oddness ("key", gear shift, gauge placement) seemingly for the sake of oddness. I didn't like any.The Hondas (Civic hybrid and the Insight we own) maybe don't get quite as good of mileage (though our Insight has averaged 46 mpg over 46k miles) and the interiors are far from luxurious but they feel like actual cars. I dare say that, while slow, our Insight is actually rather fun to drive.The Fords (Fusion and Escape)I liked. The Fusion in particular. I drove one pretty extensively for work for about two years. I liked everything about it except the sound the directional light made. That's high praise considering I have never been a Ford guy. They are very efficient (I averaged low to mid 40s in the Fusion with mostly highway driving), comfortable, quiet and feel like an actual car. The hybrid Fusion drove exceptionally well - way better than the 4 cylinder Fusion that I had as a rental car once.I REALLY like the C-Max. It destroys the Prius V in every way. It's really efficient, relatively quick, fun to drive according to reviews, spacious, has nice features/options and is priced well.I "built" one on Ford's website today and I could get one with everything I want for just over $25k, assuming dealers aren't gouging at this point. That's a base model with a couple small options like splash guards. I really like the moonroof but don't think I would tack on over $1200 for it. It's not the sexiest car, in fact is rather homely, but that's part of the appeal. It has a very European look to me that fits well with the One Ford idea.
This has winner written all over it. It's priced well, it's efficient, and it's practical. Plus, it's supposed to feel like a normal car. When I had my Prius rental, it was almost as if Toyota was intentionally trying to make the car drive as poorly as possible. If Ford can convince Prius drivers to take one of these for a spin, they'll get a lot of conquest sales.
------------------------------You can have an opinion, just be prepared to be relentlessly mocked for it.Warning: This post may cause cancer in the state of California.
Not a surprise that the better vehicle actually sells better for once. Very impressive sales for the first full month.
_______________________________Have you driven a Coyote... lately? The beer can that tows your Chevy or Fiat/Chrysler.
Way more attractive than the Prius V
Cars I've Owned:1990 Geo Storm 2+2 (Previous)2005 Dodge Neon SXT (Previous)1995 K1500 Z71 (Previous)2012 VW Golf 2.5l (Previous)2004 Land Rover Discovery (Current)2005 Land Rover LR3 HSE (Current)
"oddness ("key", gear shift, gauge placement)"for someone with long legs the Prius Gen2 would probably break knee caps in accidents :|
--------------------I'm working on a scifi-adventure webcomic!


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|Publication number
|Publication type
|Application number
|Publication date
|Nov 14, 1989
|Filing date
|Sep 24, 1987
|Priority date
|Sep 24, 1987
|Fee status
|Publication number
|John L. Haslam, Gerald S. Rork
|Original Assignee
|Merck & Co., Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (12), Non-Patent Citations (2), Referenced by (24), Classifications (11), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
Diltiazem hydrochloride is a calcium ion influx inhibitor which is commercially utilized in the treatment of angina pectoris due to coronary artery spasm and chronic stable angina.
Controlled delivery devices for therapeutically active agents are well known in the art. Generally, these devices may be characterized as either diffusion controlled delivery systems or osmotic dispensing devices. U.S. Pat. No. 3,538,214 discloses a diffusion controlled device in which a tablet core containing an active ingredient is surrounded by a water insoluble coating which contains film modifying agent soluble in the external fluids in the gastrointestinal tract. An example of an osmotic device is described in U.S. Pat. Nos. 3,845,770 and 3,916,899 which is a core composition of an active agent and an osmotically effective solute which is enclosed by an insoluble semipermeable wall having a release means. Numerous modifications to these types of delivery devices have been described in the art in an effort to improve their release characteristics.
The use of pore formers in substantially water impermeable polymers, such as polyvinyl chloride, is disclosed in J. Pharm. Sci. 72, 772-775 and U.S. Pat. No. 4,244,941. The devices release the core contents by simple diffusion through the pores in the coating.
U.S. Pat. No. 3,957,523 discloses a device which has pH sensitive pore formers in the wall.
U.S. Pat. No. 4,256,108; 4,160,452; 4,200,098 and 4,285,987 disclose devices with pore formers in only one of at least two wall layers. These devices contain a drilled hole for the release of the core contents.
Co-pending U.S. Pat. applications Attorney Docket Number IX112IB and IX112IC disclose systems which comprise an inner core compartment of osmotically active composition surrounded by an enclosing controlled porosity wall material that is substantially permeable to both solute and external fluid. These systems are osmotic dispensing devices for a broad range of therapeutically active agents. However, the delivery of a highly soluble agent from these devices at a constant rate is difficult to achieve.
U.S. Pat. No. 4,326,525 addresses the problem of delivering an active agent from an osmotic device by incorporating into the core a buffer which enters into a proton-transfer or neutralization reaction with the agent thereby producing an aqueous soluble agent salt within the device.
This invention concerns an osmotically activated system for dispensing diltiazem L-malate, as the pharmacologically active agent, to biological receptor sites over a prolonged period of time. The system comprises an inner core compartment of osmotically active composition surrounded by an enclosing wall material. The core comprises diltiazem L-malate and sodium bitartrate, which exhibit unique solubility characteristics in an external fluid, and an osmotic pressure gradient across the wall against the external fluid. The wall constitutes a layer of controlled porosity that is substantially permeable to both the external fluid and the aqueous solution of the core composition. Diltiazem L-malate and sodium bitartrate are released from the system in a nearly pH independent manner by external fluid imbibition through the wall into the inner core compartment at a rate controlled by the wall composition and dimensions, producing a solution containing core composition that is released through the wall at a controlled rate in response to fluid volume flux, dV/dt, resulting from the osmotic pressure gradient, and diffusive flux, (dM/dt)D, driven by the chemical potential gradient of the core composition across the wall. The total rate of release, (dM/dt)T, is given by Equation 1 where C is the concentration ##EQU1## of the active agent in the dissolved core composition and remains constant when excess solid core mass is present. In the present invention the volume flux contribution, (dV/dt)C, to the total rate is expected to be greater than the diffusive contribution, (dM/dt)D, and forms the basis for the osmotic pump action of the device.
The present invention include osmotic systems that are readily manufactureable to deliver a pre-determined dose of agent at a programmed rate from compositions of matter in the varied geometries and sizes of tablets, and such related dosage forms as familiar to those skilled in the art for oral, buccal, vaginal, rectal, nasal, ocular, parenteral and related routes of administration. The invention also provides osmotic systems that deliver agent on an equivalent mass per unit surface area basis.
FIG. 1 is an embodiment of the osmotic pump.
FIG. 2 is the release profile (statistical average of several pumps) of the pumps produced in Example 1.
FIG. 3 is the release profile (statistical average of several pumps) of the pumps produced in Example 2.
FIGS. 4A through 4D are the release profiles (statistical average of several pumps) of the pumps produced in Example 3 formulations 3A through 3D, respectively.
The instant invention is directed to an osmotic pump, for the controlled release of diltiazem L-malate to an environment of use, said pump comprising:
(A) a core which comprises a therapeutically effective amount of diltiazem L-malate and an effective buffering amount of sodium bitartrate surrounded by
(B) a rate controlling water insoluble wall, having a fluid permeability of 6.96×10-18 to 6.96×10-14 cm3 sec/g and a reflection coefficient of less than 0.5, prepared from:
(i) a polymer permeable to water but impermeable to solute and
(ii) 0.1 to 60% by weight, based on the total weight of (i) and (ii), of at least one pH insensitive pore forming additive dispersed throughout said wall.
The osmotically active core composition mass (3) of FIG. 1, is typically in the form of a solid conventional tablet. The core is completely encased by the controlled porosity wall (2). The core is comprised of a mixture of diltiazem L-malate and sodium bitartrate, as well as other inert pharmaceutically acceptable carriers, which are not osmotically effective agents (4, 5, etc.) combined to give the desired manufacturing and ultimate agent(s) delivery characteristics.
The preferred specifications for the core are summarized below and include:
______________________________________1. Core Loading 0.05 nanograms to 5 grams (size) or more (includes dosage forms for humans and animals)2. Osmotic about 10-22 atmospheres pressure are developed from the developed mixture of diltiazem by a solution L-malate and sodium of the core bitartrate; however osmotic pressures greater than zero are within guidelines3. Core solubility to get continuous, uniform release (zero-order kinetics) of 50% or greater of the initially loaded core mass, the ratio of the core mass solubility, S, to the core mass density, ρ, that is S/ρ, must be 0.5 or lower. Typically this occurs when 50% of the initially loaded core mass saturates a volume of external fluid equal to the total volume of the initial core mass.______________________________________
S/ρ ratios less than 0.5 fall within the workings of the invention and result in higher percentages of initial core mass delivered under zero-order kinetics. S/ρ can be selected to give acceptable combined characteristics of stability, release rate, and manufacturability.
In the present invention diltiazem L-malate, as the active agent, when combined with an effective buffering amount of sodium bitartrate has the desired solubility, osmotic pressure, density, stability, and manufacturability characteristics. The effective buffering amount of sodium bitartrate is an amount sufficient to: (a) provide greater than 50% of the drug release zero order and (b) hold the pH dependence of drug release to less than ±20% when the percent drug release in water is compared with drug release over the pH range of 1.2 to 7.5. About 80 percent by weight of sodium bitartrate to diltiazem L-malate has been found to be the minimum amount sufficient as an effective buffering amount.
There is no critical upper limit as to the total amount of drug plus buffer that can be incorporated into a core mass and typically will follow the core loading (size) specification 1. However, the maximum amount of diltiazem L-malate contained in the core composition should not exceed the amount which is necessary to deliver the equivalent amount of diltiazem hydrochloride recommended for approved therapeutic uses. The lower limit ratio of diltiazem L-malate and sodium bitartrate to other inert pharmaceutically acceptable carriers is dictated by the desired osmotic activity of the core composition, the desired time span of release, and the pharmacological activity of the active agent. Generally the core will contain 0.01% to 90% by weight or higher, of a mixture of diltiazem L-malate, as the active agent and sodium bitartrate with other inert pharmaceutically acceptable carriers. The solubilized constituents create a water activity gradient across the wall, (2), of FIG. 1, resulting in osmotically actuated fluid movement constituting the osmotic pump action of the invention.
The amount of diltiazem L-malate, as the active agent and sodium bitartrate alone or admixed with other inert pharmaceutically acceptable carriers present in the device is initially in excess of the amount that can be dissolved in the fluid that enters the reservoir. Under this physical state when the agent is in excess, the device will osmotically operate to give a substantially constant rate of release. The rate of agent release pattern can also be varied by having different amounts of agent in the reservoir to form solutions containing different concentrations of agent for delivery from the device. Generally, the device can house from 0.05 ng to 5 grams or more, with individual devices containing, for example, 25 ng, 1 mg, 5 mg, 250 mg, 500 mg, and the like.
As a specific embodiment of the present invention, the diltiazem L-malate in the core is between 30 and 500 mg and as another specific embodiment of the present invention, the sodium bitartrate in the core is between 30 and 500 mg.
The resulting device will have a water permeability driven by a saturated solution of diltiazem L-malate, as the active agent and sodium bitartrate at the temperature of use, of 0.01 ml per cm2 of surface area per day to 10 ml per cm2 of surface area per hour.
The controlled porosity wall of the present invention is substantially permeable to both solute and external fluid. The wall is composed of materials that maintain their physical and chemical integrity during the controlled dispensing of agent in mixture with materials that can be leached into the external fluid. The wall has programmable fluid transmission rate which provide for controlled release of agent which is nearly free from environmental influences including pH and degree of external fluid agitation.
The wall may be composed of either insoluble, non-erodible materials mixed with leachable additives, or bioerodible materials containing leachable additives. Bioerodible materials would be selected to bioerode after a predetermined period with bioerosion occurring subsequent to the period of agent release.
The phrase "permeable to water but impermeable to solutes" means the water permeates through the polymer preferably to solute, under a pressure differential.
Referring to FIG. 1, the osmotic pump device (1) is typically in the form of a single coated tablet or shaped for rectal or vaginal applications.
The water insoluble, permeable wall (2) of controlled porosity may be applied to osmotically active core composition masses (3) by spray coating procedures. The wall is comprised of (a) polymeric material that is insoluble in the fluids of the environment of intended use (usually water); (b) other added excipients that will dissolve in the environmental fluids and leach out of the wall. The leached wall is a sponge-like structure composed of numerous open and closed cells that form a discontinuous interwoven network of void spaces when viewed with a scanning electron microscope. This controlled porosity wall serves as both the water entry and core composition solution exit sites. The wall is permeable to both water and solutes, and as constituted in the environment of use has a small solute reflection coefficient, σ, and displays poor semipermeable characteristics when placed in a standard osmosis cell.
The specifications for the wall are summarized below and include:
______________________________________1. Fluid Permeability 6.96 × 10-18 to 6.96 × of the wall 10-14 cm3 sec/g (equivalent to 10-5 to 10-1 cm3 mil/cm2 hr atm)2. Reflection Microporous coats to Coefficient have a reflection coefficient, σ, defined as:hydrostatic pressure difference ##STR1##hydrostatic volume flux where σ is less than 1, usually 0 to______________________________________0.8.
A specific embodiment of the present invention are those osmotic pumps wherein the reflection coefficient of the wall is less than 0.5. Exemplifying this embodiment are those osmotic pumps wherein the reflection coefficient of the wall is less than 0.1.
Additional, preferred specifications for the wall include:
______________________________________1. Plasticizer and 0 to 50, preferably 0.001 Flux Regulating to 50, parts per 100 parts Additives wall material2. Surfactant 0 to 40, preferably .001 Additives to 40, parts per 100 parts wall material3. Wall l to 1,000, preferably 20 Thickness to 500, microns typically although thinner and thicker fall within the invention4. Microporous 5% to 95% pores between Nature 10 angstroms and 100 microns diameter5. Pore forming 0.1 to 60%, preferably 0.1 Additives to 50%, by weight, based on the total weight of pore forming additive and polymer, pH insensitive pore forming additive, preferably: (a) 0.1 to 50%, preferably 0.1 to 40%, by weight solid additive (b) 0.1 to 40% by weight liquid additive But no more than 60% total pore formers.______________________________________
The water insoluble wall of the instant invention must not be covered on its inner or outer surface by a layer of material that is impermeable to dissolved solutes within the core during the period of pumping operation.
Any polymer film by itself permeable to water but impermeable to solutes as previously defined may be used. However, the film may be covered initially by a rapidly dissolving coat used for aesthetic purposes or containing a second drug substance. Examples include cellulose acetate having a degree of substitution, D.S., meaning the average number of hydroxyl groups on the anhydroglucose unit of the polymer replaced by a substituting group, up to 1 and acetyl content up to 21%; cellulose diacetate having a D.S. of 1 to 2 and an acetyl content of 21 to 35%; cellulose triacetate having a D.S. of 2 to 3 and an acetyl content of 35 and 44.8%; cellulose propionate having an acetyl content of 1.5 to 7% and a propionyl content of 2.5 to 3% and an average combined propionyl content of 39.2 to 45% and a hydroxyl content of 2.8 to 5.4% cellulose acetate butyrate having a D.S. of 1.8, an acetyl content of 13 to 15%, and a butyryl content of 34 to 39%; cellulose acetate having an acetyl content of 2 to 99.5%, a butyryl content of 17 to 53%, and a hydroxyl content of 0.5 to 4.7%; cellulose triaceylates having a D.S. of 2.9 to 3 such as cellulose trivalerate, cellulose trilaurate, cellulose tripalmitate, cellulose trisuccinate, cellulose triheptylate, cellulose tricaprylate, cellulose trioctanoate, and cellulose tripropionate; cellulose diesters having a lower degree of substitution and prepared by the hydrolysis of the corresponding triester to yield cellulose diacylates having a D.S. of 2.2 to 2.6 such as cellulose dicaprylate and cellulose dipentanate; and esters prepared from acyl anhydrides or acyl acids in an esterification reaction to yield esters containing different acyl groups attached to the same cellulose polymer such as cellulose acetate valerate, cellulose acetate succinate, cellulose propionate succinate, cellulose acetate octanoate, cellulose valerate palmitate, cellulose acetate palmitate and cellulose acetate heptanoate.
Additional polymers that can be used for the purpose of the invention include cellulose acetate acetoacetate, cellulose acetate chloroacetate, cellulose acetate furoate, dimethoxyethyl cellulose acetate, cellulose acetate carboxymethoxypropionate, cellulose acetate benzoate, cellulose butyrate naphthylate, cellulose acetate benzoate, methylcellulose acetate methylcyanoethyl cellulose, cellulose acetate methoxyacetate, cellulose acetate ethoxyacetate, cellulose acetate dimethylsulfamate, ethylcellulose, ethylcellulose dimethylsulfamate, cellulose acetate p-toluene sulfonate, cellulose acetate methylsulfonate, cellulose acetate dipropylsulfamate, cellulose acetate butylsulfonate, cellulose acetate laurate, cellulose stearate, cellulose acetate methylcarbamate, agar acetate, amylose triacetate beta glucan acetate, beta glucan triacetate, acetaldehyde dimethyl acetate, cellulose acetate ethyl carbamate, cellulose acetate phthalate, cellulose acetate dimethyl aminoacetate, cellulose acetate ethyl carbonate, poly (vinyl methyl) ether copolymers, cellulose acetate with acetylated hydroxyethyl cellulose hydroxylated ethylenevinylacetate, poly (ortho ester)s, polyacetals, semipermeable polyglycolic or polylactic acid and derivatives thereof, selectively permeable associated polyelectrolytes, polymers of acrylic and methacrylic acid and esters thereof. film forming materials with a water sorption of one to fifty percent by weight at ambient temperatures with a presently preferred water sorption of less than thirty percent, acylated polysaccharides, acylated starches, aromatic nitrogen containing polymeric materials that exhibit permeability to aqueous fluids, membranes made from polymeric epoxides, copolymers of alkylene oxides and alkyl glycidyl ethers, polyurethanes, and the like. Admixtures of various polymers may also be used.
The polymers described are known to the art or they can be prepared according to the procedures in Encyclopedia of Polymer Science and Technology, Vol. 3, pages 325 to 354, and 459 to 549, published by Interscience Publishers, Inc., New York, in Handbook of Common Polymers by Scott, J. R. and Roff, W. J., 1971, published by CRC Press, Cleveland, Ohio; and in U.S. Pat. Nos. 3,133,132; 3,173,876; 3,276,586; 3,541,055; 3,541,006; and 3,546,142.
A controlled porosity wall can be generically described as having a sponge-like appearance. The pores can be continuous pores that have an opening on both faces of a microporous lamina, pores interconnected through tortuous paths of regular and irregular shapes including curved, curved-linear, randomly oriented continuous pores, hindered connected pores and other porous paths discernible by microscopic examination. Generally, microporous lamina are defined by the pore size, the number of pores, the tortuosity of the microporous path and the porosity which relates to the size and number of pores. The pore size of a microporous lamina is easily ascertained by measuring the observed pore diameter at the surface of the material under the electron microscope. Generally, materials possessing from 5% to 95% pores and having a pore size of from 10 angstroms to 100 microns can be used.
Any pH insensitive pore forming additives may be used in the instant invention. The microporous wall may be formed in situ, by a pore-former being removed by dissolving or leaching it to form the microporous wall during the operation of the system. The pores may also be formed in the wall prior to operation of the system by gas formation within curing polymer solutions which result in voids and pores in the final form of the wall. The pore-former can be a solid or a liquid. The term liquid, for this invention embraces semi-solids, and viscous fluids. The pore-formers can be inorganic or organic. The pore-formers suitable for the invention include pore-formers than can be extracted without any chemical change in the polymer. Solid additives include alkali metal salts such as sodium chloride, sodium bromide, potassium chloride, potassium sulfate, potassium phosphate, sodium benzoate, sodium acetate, sodium citrate, potassium nitrate and the like. The alkaline earth metal salts such as calcium chloride, calcium nitrate, and the like. The transition metal salts such as ferric chloride, ferrous sulfate, zinc sulfate, cupric chloride, and the like. Water may be used as the pore-former. The pore-formers include organic compounds such as saccharides. The saccharides include the sugars sucrose, glucose, fructose, mannose, galactose, aldohexose, altrose, talose, lactose, monosaccharides, disaccharides, and water soluble polysaccharides. Also, sorbitol, mannitol, organic aliphatic and aromatic oils, including diols and polyols, as exemplified by polyhydric alcohols, poly(alkylene glycols), polyglycols, alkylene glycols, poly(α,ω)alkylenediols esters or alkylene glycols poly vinylalcohol, poly vinyl pyrrolidone, and water soluble polymeric materials. Pores may also be formed in the wall by the volatilization of components in a polymer solution or by chemical reactions in a polymer solution which evolves gases prior to application or during application of the solution to the core mass resulting in the creation of polymer foams serving as the porous wall of the invention. The pore-formers are nontoxic, and on their removal channels are formed that fill with fluid. The channels become a transport path for fluid. In a preferred embodiment, the non-toxic pore-forming agents are selected from the group consisting of inorganic and organic salts, carbohydrates, polyalkylene glycols, poly(α, ω) alkylenediols, esters of alkylene glycols, and glycols, that are used in a biological environment.
The microporous materials can be made by etched nuclear tracking, by cooling a solution of flowable polymer below the freezing point with subsequent evaporation of solvent to form pores, by gas formation in a polymer solution which upon curing results in pore formation, by cold or hot stretching at low or high temperatures until pores are formed, by leaching from a polymer a soluble component by an appropriate solvent, by ion exchange reaction, and by polyelectrolyte processes. Processes for preparing microporous materials are described in Synthetic Polymer Membranes, by R. E. Kesting, Chapters 4 and 5, 1971, published by McGraw Hill, Inc.; Chemical Reviews, Ultrafiltration, Vol. 18, pages 373 to 455, 1934; Polymer Eng. and Sci., Vol. 11, No. 4, pages 284 to 288, 1971; J. Appl. Poly. Sci., Vol. 15, pages 811 to 829, 1971; and in U.S. Pat. Nos. 3,565,259; 3,615,024; 3,751,536; 3,801,692; 3,852,224; and 3,849,528.
It is generally desirable from a preparation standpoint to mix the polymer in a solvent. Exemplary solvents suitable for manufacturing the wall of the osmotic device include inert inorganic and organic solvents that do not adversely harm the core, wall, and the materials forming the final wall. The solvents broadly include members selected from the group consisting of aqueous solvents, alcohols, ketones, esters, ethers, aliphatic hydrocarbons, halogenated solvents, cycloaliphatic, aromatics, heterocyclic solvents and mixtures thereof.
Exemplary plasticizers suitable for the present purpose include plasticizers that lower the temperature of the second-order phase transition of the wall or the elastic modulus thereof; and also increase the workability of the wall, its flexibility and its permeability to fluid. Plasticizers operable for the present purpose include both cyclic plasticizers and acyclic plasticizers. Typical plasticizers are those selected from the group consisting of phthalates, phosphates, citrates, adipates,tartrates, sebacates, succinates, glycolates, glycerolates, benzoates, myristates, sulfonamides, and halogenated phenyls. Generally, from 0.001 to 50 parts of a plasticizer or a mixture of plasticizers are incorporated into 100 parts of wall forming material.
Suitable plasticizers can be selected for blending with the wall forming materials by selecting plasticizers that have a high degree of solvent power for the materials, are compatible with the materials over both the processing and use temperature range exhibit permanence as seen by their strong tendency to remain in the plasticized wall, impart flexibility to the material and are non-toxic to animals, humans, avians, fishes and reptiles. Procedures for selecting a plasticizer having the described characteristics are disclosed in the Encyclopedia of Polymer Science and Technology, Vol. 10, pages 228 to 306, 1969, published by John Wiley & Sons, Inc. Also, a detailed description pertaining to the measurement of plasticizer properties including solvent parameters and compatibility such as the Hildebrand solubility parameter δ, the Flory-Huggins interaction parameter χ, and the cohesive-energy density, CED, parameters are disclosed in Plasticization and Plasticizer Processes, Advances in Chemistry Series 48, Chapter 1, pages 1 to 26, 1965, published by the American Chemical Society. The amount of plasticizer added generally is an amount sufficient to produce the desired wall and it will vary according to the plasticizer and the materials. Usually about 0.001 part up to 50 parts of plasticizer can be used for 100 parts of wall material.
The expressions "flux regulator agent", "flux enhancing agent" and "flux decreasing agent" as used herein mean a compound that when added to a wall forming material assists in regulating the fluid permeability of flux through the wall. The agent can be preselected to increase or decrease the liquid flux. Agents that produce a marked increase in permeability to fluid such as water, are often essentially hydrophilic, while those that produce a marked decrease to fluids such as water, are essentially hydrophobic. The flux regulators in some embodiments also can increase the flexibility and porosity of the lamina. Examples of flux regulators include polyhydric alcohols and derivatives thereof, such as polyalkylene glycols of the formula H--(O--alkylene)n --OH wherein the bivalent alkylene radical is straight or branched chain and has from 1 to 10 carbon atoms and n is 1 to 500 or higher. Typical glycols include polyethylene glycols 300, 400, 600, 1500, 1540, 4000 and 6000 of the formula H--(OCH2 CH2)n --OH wherein n is respectively 5 to 5.7, 8 2 to 9.1, 12.5 to 13.9, 29 to 36, 29.8 to 37, 68 to 84, and 158 to 204. Other polyglycols include the low molecular weight glycols such as polypropylene, polybutylene and polyamylene.
The amount of flux regulator added to a material generally is an amount sufficient to produce the desired permeability, and it will vary according to the lamina forming material and the flux regulator used to modulate the permeability. Usually from 0.001 parts up to 50 parts, or higher of flux regulator can be used to achieve the desired results.
Surfactants useful for the present purpose are those surfactants, when added to a wall forming material and other materials, aid in producing an integral composite that is useful for making the operative wall of a device. The surfactants act by regulating the surface energy of materials to improve their blending into the composite. This latter material is used for manufacturing devices that maintain their integrity in the environment of use during the agent release period. Generally, the surfactants are amphoteric molecules comprised of a hydrophobic part and a hydrophilic part. The surfactants can be anionic, cationic, nonionic or amphoteric, and they include anionics such as sulfated esters, amides. alcohols, ethers and carboxylic acids; sulfonated aromatic hydrocarbons, aliphatic hydrocarbons, esters and ethers; acylated amino acids and peptides; and metal alkyl phosphates; cationic surfactants such as primary, secondary, tertiary and quaternary alkylammonium salts; acylated polyamines; and salts of heterocyclic amines, arylammonium surfactants such as esters of polyhydric alcohols; alkoxylated amines; polyoxyalkylene; esters and ethers of polyoxyalkylene glycols; alkanolamine fatty acid condensates; tertiary acetylamic glycols; and dialkyl polyoxyalkylene phosphates; and ampholytics such as betamines; and amino acids.
The osmotic pump according to the present invention may also further comprise an external layer of a pharmaceutically acceptable carrier and a therapeutically effective amount of a cardiovascular agent.
Illustrative of such an osmotic pump according to the present invention are those in which the cardiovascular agent is selected from alpha receptor blocking agents, alpha and beta receptor blocking agents, angiotensin converting enzyme inhibitors, antianginal agents, antiarrhythmics, antiembolus agents, antihypertensives, beta blocking agents, digitalis, hemorheologic agents, inotropic agents, myocardial infarction prophylaxis, quinidine, cerebral vasodilators, coronary vasodilators, peripheral vasodilators, and vasopressors.
Exemplifying such an osmotic pump according to the present invention are those in which the cardiovascular agent is selected from angiotensin converting enzyme inhibitors. Such angiotensin converting enzyme inhibitors include, without limitation, captopril, enalapril and lisinopril.
The following examples illustrate the preparation of the drug-delivery devices of this invention and their controlled release of one or more therapeutically active ingredients into an environment of use and as such are not to be considered as limiting the invention set forth in the claims appended hereto.
Tablet for the osmotically controlled release of the beneficial drug diltiazem were made as follows: to a mixing bowl was added 262 g of diltiazem L-malate and 305 sodium bitartrate monohydrate which were then mixed. A solution of 37 g of Povidone K29-32 was prepared in 92 g of water and then added to the powders while mixing. The resultant dough was passed through an extruder using an 0.5 mm screen onto a tray and let dry overnight.
The granulation was then dried for 6 hours at 60° C. The dry granulation was forced through a series of screens to a final 30 mesh screen. Some of this material (67.3 g) was then mixed with 1.4 g of purified stearic acid USP for one minute. Tablets were prepared using a Stokes® Model F press fitted with 3/8 inch deep concave punches. The tablet weight was 340 mg.
Fifty of these tablets were coated in a small pan coater (8" HCT-Mini Hi-Coater® ) along with 400 cc of filler tablets (5/16" tablets made with lactose, starch, Avicel® PH101and magnesium stearate). The coating solution was prepared by adding 18 g of cellulose acetate (CA-320S) and 18 g of cellulose acetate (CA-394-60S) to a 4 1 erlenmeyer flask containing 490 ml of methylene chloride. After all the polymer particles were dispersed, 300 ml of methanol was added and the solution stirred and warmed to dissolve the polymers.
The 19 g of Sorbitol was dissolved in a 250 ml erlenmeyer flask by the addition of 40 ml of water and 130 ml of methanol. This solution was added to the polymer solution slowly with mixing. Finally 7.2 g of polyethylene glycol 400 was added and thoroughly mixed to give the final coating solution.
The filler and active tablets were placed in the coating pan and heated air was passed through the tablet bed. The pan was rotated at 28 rpm. When the outlet temperature reached 30° C., the coating solution was applied through a atomizing nozzle at 20 ml/min with atomizing air at 1.4 Kg/cm2 . The inlet air temperature was maintained between 60°-70° C. to keep the outlet temperature at 30° C. Sufficient coating solution (800-900 ml) was applied to give approximately 300 micron coat on the active tablets. The active tablets were then dried in an oven for 18 hours at 45° C.
The release profiles of these tablets in pH 1.2 hydrochloric acid (with 2 g/l of sodium chloride), water, and a 0.05M phosphate solution at pH 7.5 are shown in FIG. 2. A standard USP dissolution setup was used with a stirring rate of 100 rpm and bath temperature of 37° C. Continuous flow UV monitoring at 270 nm of diltiazem was used. The percent release was calculated from the final reading after the tablets were broken open.
To show the beneficial effect of the sodium bitartrate another batch of tablets was prepared without the sodium bitartrate. A wet granulation of 9 g of diltiazem L-malate was prepared by adding an aqueous solution of 0.8 g povidone K29-32 in 3.5 ml of water. This was forced through a number 14 mesh screen and let dry several hours at 30° C. and then overnight at 60° C. The material was then forced through several screens, the final one being 25 mesh. The purified stearic acid USP (160 mg) was added to 8 g of the dry granulation and mixed in a bottle. Tablets were made using a Stokes® Model F press with 1/4 inch deep concave punches. The tablet weight was 156 mg.
These tablets were coated using the same coating procedure described in Example 1 with the same coating solution formula. A coat of 81 microns was applied to these tablets which were then dried at 45° C. overnight.
The release profile of the drug from these tablets are shown in Figure 3. The same release media and the same set-up as described in Example 1 were used. The effect of the sodium bitartrate in the tablet formulation can clearly be observed by the relative lack of pH dependence observed by comparing the release of drug between FIG. 2 (with sodium bitartrate) and FIG. 3 (without sodium bitartrate).
To better define the effective range of sodium bitartrate, a series of tablets with different ratios of diltiazem L-malate to sodium bitartrate were prepared. To a mixture of diltiazem L-malate and sodium bitartrate (see table below) was added 5.2 g of a solution of Povidone® K29-32 (12 g) in water (40 g) and the resultant combination mixed until homogeneous.
______________________________________ Diltiazem SodiumFormulation L-malate (g) Bitartrate (g)______________________________________3A 10 53B 10 83C 10 103D 10 15______________________________________
Each of the wet granulations was dried at 60° C. (or 4 hours and then forced through a series of screens, the final one being 30 mesh. Each of the dried granulations was weighed and 2 percent of stearic acid was added with mixing. This material was tableted using 3/8 inch deep concave punches to give tablets which contained approximately 146 mg of diltiazem L-malate.
The tablet weights were as follows:
______________________________________ Formulation______________________________________ 3A 233 mg 3B 292 mg 3C 315 mg 3D 380 mg______________________________________
The tablets were coated using the coating procedure described in Example 1. The coating thickness ranged from 365 to 435 microns.
The release profiles are shown in FIGS. 4A through 4D for the formulations 3A through 3D, respectively. The same release media and the same set-up as described in Example 1 was used.
From these results the percentage of sodium bitartrate by weight to diltiazem L-malate of about 80 percent is required to reduce the pH effects on the release profiles and thus represents the minimum effective buffering amount of sodium bitartrate. Amounts of sodium bitartrate of up to about 150 percent by weight have also been shown to be effective in buffering the pH effects on the release profiles.
To show how a cardiovascular agent such as enalapril can be combined with this diltiazem L-malate sodium bitratrate tablet the following example is given.
In view of the fact that enalapril is normally given on a once-a-day dose regimen a fast release of enalpril from the tablet would substitute for the present tablet. The fast release of enalpril would then be followed by the controlled release of diltiazem L-malate.
Diltiazem L-malate tablets were prepared as described in Example 1 and the release profiles determined as shown in FIG. 2. These tablets were then overcoated with the following solution.
______________________________________Water 250 ml.Hydroxypropyl methylcellulose E-5 12.5 gEnalapril Maleate 12.5 gSodium bicarbonate 6.25 g______________________________________
A 400 ml beaker containing 150 ml of water was heated on a hot plate to 80° C. The HPMC-E5 was suspended in the hot water by vigorous stirring and then cooled in an ice water bath to room temperature. Stirring continued until complete solution was achieved. The enalapril maleate was suspended in 100 ml of water in a 400 ml beaker and small amounts of the sodium bicarbonate were added with stirring. Additional amounts were added as the effervescence slowed until all the bicarbonate was added. The enalapril solution was then added to the polymer solution and thoroughly mixed. This solution was applied to the diltiazem L-malate tablets using the pan coater described in Example 1. The conditions for coating this aqueous solution are as follows: 400 cc of filter tablets, inlet temperature 70°-80° C., outlet 32°-34° C., coating solution pumping rate, 4-5 ml/min, atomizing air pressure 1.6 kg/cm2 and pan rotation 30 rpm.
The weight of the tablets was checked from time to time so that when 21-25 mg. was applied to the tablet (˜10 mg enalapril maleate) the coating was terminated. The tablets were then dried 18 hours at 45° C. and then 4 hours at 60° C. to remove any remaining solvent.
The release properties were determined using the standard U.S.P. set up with paddle rotation at 100 rpm. The release of enalapril was very rapid with essentially all of the drug released in 5 minutes. The release profile of diltiazem from these tablets was not changed from that observed with tablets not coated with HPMC E-5 and enalapril maleate.
|Cited Patent
|Filing date
|Publication date
|Apr 22, 1969
|Nov 3, 1970
|Merck & Co Inc
|Controlled release medicinal tablets
|Jun 5, 1972
|Nov 5, 1974
|Alza Corp
|Osmatic dispensing device for releasing beneficial agent
|Feb 7, 1974
|Nov 4, 1975
|Alza Corp
|Osmotic dispensing device with maximum and minimum sizes for the passageway
|Mar 28, 1974
|May 18, 1976
|Shinetsu Chemical Company
|Coating compositions for solid medicines
|Apr 7, 1977
|Jul 10, 1979
|Alza Corporation
|Osmotic system having laminated wall comprising semipermeable lamina and microporous lamina
|Oct 23, 1978
|Apr 29, 1980
|Alza Corporation
|Osmotic system with distribution zone for dispensing beneficial agent
|Oct 23, 1975
|Jan 13, 1981
|Gist-Brocades N.V.
|Controlled release composition and process for preparing same
|May 21, 1979
|Mar 17, 1981
|Alza Corporation
|Microporous-semipermeable laminated osmotic system
|Nov 1, 1979
|Aug 25, 1981
|Alza Corporation
|Process for manufacturing device with dispersion zone
|Oct 14, 1980
|Apr 27, 1982
|Alza Corporation
|Osmotic device that improves delivery properties of agent in situ
|Aug 6, 1986
|Sep 29, 1987
|Warner-Lambert Company
|Method for using diltiazem for treating stroke
|Jan 3, 1986
|May 31, 1988
|Enquay Pharmaceutical Associates
|Synthetic resin matrix system for the extended delivery of drugs
|Citing Patent
|Filing date
|Publication date
|Dec 4, 1997
|Jun 13, 2000
|Ranbaxy Laboratories Limited
|Controlled drug delivery system for diltiazem
|Feb 15, 2000
|Oct 15, 2002
|Microsolutions, Inc.
|Osmotic pump delivery system with flexible drug compartment
|Jul 20, 1998
|Feb 25, 2003
|Andrx Pharmaceuticals, Inc.
|Diltiazem controlled release formulation and method of manufacture
|Jun 21, 2000
|Apr 29, 2003
|Mutual Pharmaceutical Co., Inc.
|Stable formulations of ACE inhibitors, and methods for preparation thereof
|Apr 19, 2001
|Oct 14, 2003
|Microsolutions, Inc.
|Implantable osmotic pump
|Apr 12, 2001
|Oct 21, 2003
|Wockhardt Limited
|Composition for pulsatile delivery of diltiazem and process of manufacture
|Aug 19, 2003
|Sep 12, 2006
|Eveready Battery Company, Inc.
|Razor having a microfluidic shaving aid delivery system and method of ejecting shaving aid
|May 8, 2000
|Sep 19, 2006
|Biovall Laboratories International Srl
|Chronotherapeutic diltiazem formulations and the administration thereof
|Jul 1, 2004
|Mar 12, 2013
|Intellipharmaceutics Corp.
|Controlled extended drug release technology
|Jan 29, 2010
|Dec 10, 2013
|Intellipharmaceutics Corp.
|Oral multi-functional pharmaceutical capsule preparations of proton pump inhibitors
|Jun 3, 2004
|Aug 12, 2014
|Intellipharmaceutics Corp.
|Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient
|May 14, 2007
|Jul 14, 2015
|Isa Odidi
|Pharmaceutical composition having reduced abuse potential
|Apr 3, 2007
|Feb 7, 2017
|Intellipharmaceutics Corporation
|Controlled release delivery device comprising an organosol coat
|Jul 10, 2014
|May 2, 2017
|Intellipharmaceutics Corp.
|Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient
|Jan 17, 2003
|Jul 17, 2003
|Microsolutions, Inc.
|Implantable osmotic pump
|Feb 12, 2003
|Dec 4, 2003
|Spiridon Spireas
|Stable formulations of ACE inhibitors, and methods for preparation thereof
|Aug 19, 2003
|Apr 29, 2004
|Eveready Battery Company, Inc.
|Razor having a microfluidic shaving aid delivery system and method of ejecting shaving aid
|Oct 29, 2003
|Jul 29, 2004
|Noack Robert M.
|Oral extended release tablets and methods of making and using the same
|Dec 4, 2003
|Aug 12, 2004
|Spiridon Spireas
|Storage-stable and bio-stable formulations of ace inhibitors, and methods for preparation thereof
|Oct 14, 2003
|Dec 9, 2004
|Microsolutions, Inc.
|Implantable osmotic pump
|Aug 7, 2003
|Feb 10, 2005
|Temple Okarter
|Formulations and use of a beta-blocker and an ACE-inhibitor for the treatment of cardiovascular diseases
|Mar 9, 2006
|Jul 13, 2006
|Biovail Laboratories International S.R.L.
|Chronotherapeutic diltiazem formulations and the administration thereof
|Feb 4, 2008
|Sep 11, 2008
|Mutual Pharmaceutical Company, Inc.
|Stable formulations of ace inhibitors, and methods for preparation thereof
|Jul 1, 1993
|Jan 20, 1994
|Merck & Co., Inc.
|Controlled porosity osmotic enalapril pump
|U.S. Classification
|424/424, 424/468, 424/457, 424/472, 424/426
|International Classification
|Cooperative Classification
|European Classification
|Sep 11, 1989
Owner name: MERCK & CO., INC., LINCOLN AVENUE, RAHWAY, NJ A CO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:HASLAM, JOHN L.;RORK, GERALD S.;REEL/FRAME:005140/0488
Effective date: 19870918
|Apr 20, 1993
|Fee payment
Year of fee payment: 4
|Apr 17, 1997
|Fee payment
Year of fee payment: 8
|Apr 19, 2001
|Fee payment
Year of fee payment: 12


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text:
Notice: On March 31, it was announced that Statalist is moving from an email list to a forum. The old list will shut down on April 23, and its replacement, statalist.org is already up and running.
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Re: st: STATA 12 very slow compared to STATA 10
William Buchanan <email@example.com>
"email@example.com" <firstname.lastname@example.com>
Re: st: STATA 12 very slow compared to STATA 10
Tue, 12 Mar 2013 10:13:51 -0700
-h mata- There absolutely is support for looping procedures in mata, they just use a different syntax.
Sent from my iPhone
On Mar 12, 2013, at 9:46, Sara Borelli <email@example.com> wrote:
> Nick,
> thank you very much for your suggestions
> I did not use Mata before, I tried to play around with it but it seems
> it cannot be combined with loop...
> Since I have several loops in my program, would you have an example or
> suggestion of how I could implement some of my program using Mata and
> in loop?
> Thanks for any input you might have
> Sara
> On Tue, Mar 12, 2013 at 10:29 AM, Nick Cox <firstname.lastname@example.com> wrote:
>> Maarten [NB] understated the difficulty for everyone but you, as the
>> speed of Stata [NB] can depend on what else is running, how much
>> memory is available, etc., etc.
>> A quite different comment is what are you doing here and why? I see
>> lots of pushing variables in and out of Stata matrices and some
>> bootstrap sampling, so four points as you are worried about speed.
>> 0. I see no point in using Stata matrices for storing data unless you
>> want to do matrix manipulations.
>> 1. Mata matrices are faster than Stata matrices. That was true in Stata 10 too.
>> 2. When bootstrapping, it seems easiest to hold each sample in memory
>> once, process it and then throw it away.
>> 3. -mmerge- [source not given, but last updated on SSC in 2002?] is
>> long since superseded by a revised -merge-.
>> Naturally I can't comment on the rest of the program.
>> Nick
>> On Tue, Mar 12, 2013 at 1:40 PM, Sara Borelli <firstname.lastname@example.com> wrote:
>>> Hi Martin
>>> you are right, I did not ask the question correctly. I thought there
>>> was maybe a common problem for STATA 12 being slow in general that
>>> others might have encountered. I apologize for that
>>> I write here below an extract of the program I am running. If you have
>>> any insight of what is going wrong I would really appreciate it. I
>>> also tried to run the entire program using "version 10" at the
>>> beginning of the do file, but it is still very slow
>>> I let the program run all night but is still not done. When I was
>>> using STATA 10 it was taking only 15 minutes overall
>>> before this "mat define" command line I am running some glm estimation
>>> that works at usual speed
>>> mat define P=J(618,1,.)
>>> set seed 55982264
>>> forvalues x=1/500 {
>>> mat define BS_r`x'=J(618,1,.)
>>> use data1
>>> for each var of varlist v1 v2 v3 v4 ....v10 {
>>> bsample
>>> mkmat `var', mat(Z_`var'_r`x')
>>> mat BS_r`x'=BS_r`x',Z_`var'_r`x'
>>> }
>>> drop v1-v10
>>> svmat BS_r`x', names(col)
>>> gen id=_n
>>> save BS_r`x', replace
>>> use data2, clear
>>> gen id=_n
>>> mmerge id using BS_r`x'
>>> save replication `x'
>>> predict prediction`x'
>>> mkmat prediction`x', mat(P_`x')
>>> mat P=P, P_`x'
>>> }
>>> It seem to run smoothly until the "predict", but seems to get slow at
>>> the time of running the command mkmat prediction`x', mat(P_`x')
>>> thanks for any insight you might have
>> *
>> * For searches and help try:
>> * http://www.stata.com/help.cgi?search
>> * http://www.stata.com/support/faqs/resources/statalist-faq/
>> * http://www.ats.ucla.edu/stat/stata/
> *
> * For searches and help try:
> * http://www.stata.com/help.cgi?search
> * http://www.stata.com/support/faqs/resources/statalist-faq/
> * http://www.ats.ucla.edu/stat/stata/
* For searches and help try:
* http://www.stata.com/help.cgi?search
* http://www.stata.com/support/faqs/resources/statalist-faq/
* http://www.ats.ucla.edu/stat/stata/


text:
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Section 607 Reports as published in the Federal Register.
Letter to Mr. Lee Grossman
February 22, 2002
Topic: Assistance Under Other Federal Programs
Letter clarifying that the Family Educational Rights and Privacy Act, as currently written, does not allow educational agencies and institutions to disclose information from student education records to the Centers for Disease Control without prior written consent of the parent.
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text: Hello I am new here. I had 3 hives of my own when I grew up and was being taught how to handle bees. I am comfortable enough that I do not wear a suit or mesh hat. The problem arises well I do not really remember much from the days gone by. I am looking to get started I have purchased a used hive and it has 5 supers for it, 2 smokers, 1 feeder, the queen screen, well lets just say it is 100% complete minus the hive tool which I still have mine. What can I use to clean up the inside of the hive with? What Kind of paint can I use on the outside as not to deter my bees. And where can I get some bees? I am really looking forward to getting this started again. I am going to the library next week to get some books but want to get started. I live in St. Louis If anyone is close and wants to help a guy out.


text:
Style near Sagrada Familia
숙박 가능인원5
침실 수3
면적90 m²
Floor No.2(with elevator)
- 가족 / 아이들과 친근함
- 부엌
- 에어콘
- 세탁기 / 건조기
- 주차
- 엘레베이터
- 발코니/테라스
Accommodation summary
|Independencia, 08025 Barcelona, 스페인
|Acceptance rate
|Response time
|A few hours
|Calendar updated
|A week ago
The apartment consists of 2 cosy double bedrooms and a single bedroom with bed linen included. The stylish and colourful fully equipped kitchen features stainless steel appliances and the combined living/dining area has a dining table for 6. Towels are provided in the tiled bathroom and laundry facilities are available.
A UNESCO World Heritage Site, the Hospital de Sant Pau Museum is a 20-minute walk from the apartment. Encants Metro Station is within 200 meters and offers guests direct access to Antoni Gaudi's Casa Batlló Building and the modern Torre Agbar Building.
The surrounding area is vibrant with a wide range of shops, restaurants and bars.
숙소규정Parking is available for €25 per night, or €75 for 15 nights.
No pets.
No parties.
Respect the neighbors and keep noise to a minimum after 10pm.
|Weekly rate for up to 5 guests
|92356957 ₩
|Monthly rate for up to 5 guests
|258496186 ₩
|Check-in before
|환불 규정
|매우 유연함
It was a very nice and cosy appartment. And Josep was very helpfull to answer all our questions.
We liked our stay in Barcelona very much.
The appartment was nice, and well located. Supermarket and bakery around the corner. I recomment this appartment.
I stayed in the apartment with my family for three nights. The place is clean, well equipped and very spacious. It's located in a nice area, walking distance from the Sagrada Familia, and also very close to metro stations.
Josep, the owner, is very helpful, although we couldn't meet in person it was very easy to communicate via SMS.
I can sincerely recommend staying in this appartment!
The host. Mr. Josep was very responsive from the order till we left.
The apartment is not in the center but 2 min. from Metro which makes it very easy to go every where. We were 2 couples and it was very comfortable with 2 double rooms and extra one single. equipped kitchen, 2 bathrooms, nice living room and it was just perfect. It was also quiet neighborhood with many shops around, supermarkets, restaurants.
Made contact with Josep in advance or arriving. He provided details of how to get to the apartment, & waiting outside the property when we arrived.
Did a full hand over of the flat including maps of the local area shops & underground.
The flat is very well furnished with just about everything you need, including coffee, cooking oils, & tin foil. There is a dishwasher, fridge & freezer, & even a washing machine. It is without doubt the best equipped flat I have rented. It has two showers & toilets which is really usefull if four of you are staying.
Would I stop again most defiantly.
We had a great time in the apartment. The location is very good next to PT, super markets, cafe's and restaurants. And feels save at night. Sagrada within 10 minutes walk.
The apartment is well equipped. Everything you need is there. The owner is very nice and gave us a lot of information.
Shower cabines can use some maintenance. Personally I found the matressess to hard. My wive however was ok with the these.
As all the apartments in Barcelona the building is a bit noisy. Nevertheless we would advice our friends to rent the apartment.
Karin, Claudia and Frans
We really enjoyed the stay in this apartment, a family of 4 with two teenagers. The apartment was comfortable and well-equipped. A short walk to the fantastic Sagrada Familia was excellent. Although a little away from "downtown", the metro station on the corner of the building would take us where we wanted to go.
Great experience. The flat was New and big like in the description. We had a very good Trip and Joseph was helpfull to find the important things in Barcelona. With metro in 200 m distance it was relaxed. It. ist recommended to stay here, if you like travelling without trouble.
It was very nice staying. The appartament is comfortable,clean and well equipped.it is also well situated only a few minutes walk from Sagrada.The houselord is very friendly and helpful.We recomend it.
We spent five great days in Joseph's nice apartment. It's well located, a 2 minutes walk from next Metro station (enchants) and a 5 minutes walk from next train station (clots). By metro it's one station to La Sagrada Familla and 5 further ones to the town center. By train you are at the airport in around 30 Minutes. The apartment is quiet, has two bathrooms, 3 bedrooms and 5 beds and it is perfect for a family of 5. The kitchen is well equipped and saves money of the travel budget you otherwise spent in hundreds of great tapas bars in Barcelona. One big supermarket and plenty of small ones are near by, also an excellent small bakery and two vinotecas. All an in all the apartment and his nice owner are highly recommended.
Dagmar&Thomas&Family from Germany
- 확인된 숙소의 품질
- 모든 호스트는 전화로 입증되었습니다.


text:
Home › Forums › Campfire › Pre-Trip Planning › Shepherds Pass, Forester Pass, Kearsarge Pass
Jul 27, 2012 at 10:14 pm #1292394
I had originally planned on doing the Evolution Loop but because of time constraints I can't start on my original date. I read a great trip report from Ken Helwig and several from Tom Kirchner singing high praises about Shepherds Pass even though it can be quite rugged. I'd like to do the loop I mentioned in the subject line and I'm looking for any info…good campsites, lakes/areas I should visit, how far apart the two trail heads are, trail conditions, etc. I have between 4-5 days but I would like to do it in four and I'll be going solo.Jul 28, 2012 at 7:19 am #1898166
Erik a few questions…
Firstly are you solo or with a group? The reason I ask is because both trailheads are about 30 minutes apart. If you end your hike at the Shepherd Pass trailhead you will be at the valley floor where the heat can be stifling. The odds of you hitching a ride is much less than if you end it at Onion Valley. Now, if you were to end the hike at Onion Valley hitching to the road junction (I forget the name of the dirt road that takes you to Shepherd Pass trailhead…I think it is Foothill??), I don't know if anyone would be kind enough to take you the distance to your car. Just a thought.
That is why I am asking if you are solo or not.
Just saw that you mentioned solo….so what I listed is what difficulties you would have getting back to your car. You could sleep at the Shepherd Pass trailhead and then hike/hitch to your car the next day. We did this loop in 3 days and that was a perfect amount of time. If you were solo I think going over Shepherd Pass and completing the hike at Onion Valley would be more conducive for a solo hiker getting back to their car.
With that said, how strong of a hiker are you? There are two options available for you to camp along the Shepherd Pass trail. Mahogany Flat and Anvil Camp. We passed up Mahogany because it is exposed and HOT…lots of Manzanita (I think that's what it was…I was on a hiking mission at that point and was not paying attention). It's basically a "dry camp". Anvil Camp is shaded, nice and has a creek running through. Their are many places to camp and it is a nice place. Oh and a third option if you make it up that high is The Pothole. There are some nice bivy sites and you have a nice view of the crux of the pass from there. The trail is unmaintained. It is very similar to the trail that takes you from North Lake to Lamarck Col…that is a point of reference if you have hiked that before. If you are strong enough to make it over the pass, we camped at a lovely lake that is north of the trail heading down and basically situated at the middle of Diamond Mesa. It's easy to find and the view are sublime. From there to Forester camping options are rather limited and bleak. The other side of Forester has many beautiful sites once you enter the treeline. You get great views of the Bubbs Creek Drainage. The Center Basin Jct. has a nice spot with a bear box. You could spend a day there and head into Center Basin to do some exploring if you would want to expand your trip to 4 hiking days. From there it is around 7 miles to Kearsage Lakes which is situated right below Kearsarge Pass. There are many lovely sites along the lakes and it is a very beautiful area to camp. From there it is a 1000 foot climb to the pass and a fast boogie down to the trailhead. This trailhead is quite busy and would be your best best for hitching back to your car.
I hope this helps. This is just my opinion, and I am sure others will chime in. Have fun on this hike, it is a butt kicker as you tackle a pass a day, but the scenery is amazing!Jul 28, 2012 at 9:02 am #1898179
If you want to avoid hitching, you could head out over Junction Pass (pre-1930 JMT route) which links up with the Shepherd Pass trail at the Pothole.
I used this route last month, the trail on the north side of the Pass is still in surprisingly good shape, Center Basin is picturesque and the views from the top of the Center Peak ridge are fantastic, but the descent is a long gravel/scree ski followed by some boulder hopping and a bit of bushwhacking. The trail is marked approximately on the USGS topo and is reasonably accurate but be aware that the pass itself is incorrectly placed (about 1/3rd of a mile too far east).
This option will certainly be a lot less busy than Kearsarge Pass if solitude is your goal.
Ken's info on campsites is good, also just in case you don't know, there is a camping ban at Bullfrog Lake.
Feel free to ask for any more specific info,
DaveJul 28, 2012 at 9:13 am #1898180
Dave, I was going to do the Junction Pass route last year. How was the scree coming down into The Pothole. I looked at it as we headed down Shepherd Pass. Did you veer to the left as you were facing down to The Pothole where the water comes down the chute. I was trying to figure out where you would head down. As I was going up Forester I did see two hikers making there way up Junction Pass from Center Basin…Jul 28, 2012 at 9:15 am #1898181
Nathan HaysMember
@oroambulantLocale: San Francisco
If you call in to Lone Pine sporting goods store you can find someone willing to follow you to drop your car at the exit point and drive you to the hike in point. I haven't done this myself, but was just told by someone who has that the locals love to make extra bux this way.Jul 28, 2012 at 9:40 am #1898186
It's hard to know exactly where you mean, but if you're referring to the last 1/2 mile or so to the Pothole, we ended up between the two tributaries shown on the USGS topo, but this wasn't the best way; as you suggest further to the east looked a bit easier, but we dropped down a bit too early and it's easier to walk downhill through willow than traverse through it. We did however come across some decent campsites in this area.
DaveJul 28, 2012 at 12:01 pm #1898215
Thanks Dave, that is the area that I was referring to. I was looking at this section from the trail but it sounds like it is quite doable. Excited to try it in the futureJul 29, 2012 at 2:05 am #1898345
Sean FraserMember
I am planning a trip to Williamson and Tyndall with a friend in mid August 2012. We plan the Shepherds Pass approach to Williamson Bowl the first day. However, I have heard it is 'better' to start up Shepherds Creek rather than Symmes Creek and meet up with the Shepherds Pass trail near Mahogany Flat, which avoids the descent descent to Mahogony Flat on the trail up.
Seems questionable to me, as a super highway trail is usually faster than navigating a less travelled creek and canyon.
Any information on the alternate start to Shepherds Pass trail? Thanks.Jul 29, 2012 at 3:07 am #1898348
Looking down Shepherd's Creek from Mahogany Flat it seemed steep sided and thickly vegetated, I would stick with the trail.
DaveJul 29, 2012 at 7:48 am #1898368
Sean, oohhhhh I would not go that route….no way. Take the trail. Once at the pass Williamson Bowl is a stroll. Don't do itJul 29, 2012 at 6:26 pm #1898456
"I have heard it is 'better' to start up Shepherds Creek rather than Symmes Creek and meet up with the Shepherds Pass trail near Mahogany Flat, which avoids the descent descent to Mahogony Flat on the trail up.
Seems questionable to me, as a super highway trail is usually faster than navigating a less travelled creek and canyon."
Your instincts are sound. I'd recommend following them and take the trail that starts out going up Symmes Creek. It is an excellent, if strenuous, trail. When you get to the divide that separates the Symmes/Shepherd Creeks' watersheds, you can look down on Shepherd Creek and see what insanity it would be to bushwhack-scramble directly up Shepherd Creek to save a lousy 500' descent and recapture. Whoever came up with that idea either has a twisted sense of humor or is borderline nuts.Jul 29, 2012 at 6:57 pm #1898459
+1 on what Tom posted….just gain the pass, it is a stroll over to Williamson Bowl…I plan on spending many trips in this area and cannot think of going up that route.Jul 29, 2012 at 7:08 pm #1898461
I was just looking at my map and there's a section going from The Pothole to the top of the pass that's marked as "primitive" trail. I have no experience in off trail travel or route finding…what should I expect?Jul 29, 2012 at 7:13 pm #1898463
"I was just looking at my map and there's a section going from The Pothole to the top of the pass that's marked as "primitive" trail."
Which pass? Junction or Shepherd?Jul 29, 2012 at 7:15 pm #1898465
Sorry, Shepherd Pass.Jul 29, 2012 at 7:40 pm #1898469
The stretch from the Pothole up to just below the pass is rough in places, but a good trail, nonetheless. The last 600 feet or so, known as The Headwall, is a grungy mess composed of mostly small talus and scree which is falling into disrepair due to lack of TLC by the Forest Service. Still, it is a trail of sorts that zig zags up to the pass is increasingly tight, steep, unstable switchbacks. You won't have any trouble staying on route. It is well to take your time and watch your foot placement, but otherwise not a big deal. Coming down is a bit more difficult. Proceed cautiously, keeping your steps short and legs flexed, and you'll do fine.Jul 29, 2012 at 7:56 pm #1898474
+1 on what Tom wrote ….. just gain the pass and stroll over to the bowl…
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Posted: Oct 24, 2016 11:08 PM PDT
Updated: Oct 24, 2016 11:08 PM PDT
2015: Flip Saunders, the Minnesota Timberwolves' president of basketball operations and head coach, dies from Hodgkin's lymphoma at the age of 60 in Minneapolis. Saunders played collegiately at the University of Minnesota before a coaching career that went from the CBA to the NBA with the Timberwolves, Detroit Pistons and Washington Wizards. [ + - ]
2014: Scottish rock musician and singer-songwriter Jack Bruce, best known as a founding member of the British psychedelic rock trio Cream along with Ginger Baker and Eric Clapton, dies of liver disease at age 71 in Suffolk, England. [ + - ]
2013: Actress, voice artist and comedian Marcia Wallace dies of pneumonia and sepsis at the age of 70 in Los Angeles. Wallace is best known for her roles as receptionist Carol Kester on the 1970s sitcom "The Bob Newhart Show," and as the voice of elementary school teacher Edna Krabappel on "The Simpsons," which earned her an Emmy Award in 1992. [ + - ]
2010: Mount Merapi in Central Java, Indonesia, erupts in the first of what would become more than a month of eruptions. Despite more than 350,000 people being evacuated from the affected area, 353 people would be killed during the eruptions, many as a result of pyroclastic flows, fast-moving currents of superheated gas and rock. [ + - ]
2010: Sony takes its original cassette Walkman off the market. The portable audio cassette player, which made its debut in Japan on July 1, 1979, and came to America in June 1980, revolutionalized music listening habits by allowing people to carry music with them and listen to music through lightweight headphones. Sony sold some 200 million iterations of the cassette Walkman over the product line's 30-year career. [ + - ]
2003: The Cedar Fire, the second-largest fire in California history, starts south of Ramona, California, in central San Diego County. The fire would kill 15 people, consume 250,000 acres and destroy 2,200 homes around San Diego before being contained on Nov. 3, 2003. The Cedar Fire was one of 15 wildfires throughout Southern California in October 2003, which became known as the "Fire Siege of 2003." [ + - ]
2003: Florida State's Bobby Bowden passes Penn State coach Joe Paterno to become the winningest coach in major college football history with his 339th victory as the Seminoles beat Wake Forest 48-24. Bowden would finish his career in 2009 with 389 career wins, but Florida State was later forced to vacate 12 wins from the 2006 and 2007 seasons in relation to an academic scandal, dropping him to No. 2 behind Paterno with 377 wins. [ + - ]
2002: Irish actor Richard Harris, perhaps best known for his role as King Arthur in the 1967 film "Camelot" and for playing Albus Dumbledore in the first two films in the "Harry Potter" series, dies of Hodgkin's lymphoma at the age of 72 in London, England. His other films included "The Sporting Life" and "The Field," both of which earned him Oscar nominations, "Gladiator," "Unforgiven" and "Cry, the Beloved Country." [ + - ]
2002: U.S. Sen. Paul Wellstone, a Democrat from Minnesota, dies in an airplane crash in northern Minnesota along with seven others, including his wife, Sheila, and their daughter, Marcia. Wellstone's death came just 11 days before the 2002 U.S. Senate election in which he was running for a third term. The Minnesota Democratic-Farmer-Labor Party selected former Vice President Walter Mondale to compete with Norm Coleman in the general election, with Coleman winning election. [ + - ]
1999: Professional golfer Payne Stewart and five others are killed when their Learjet crashes in South Dakota. National Transportation Safety Board investigators would later conclude that the plane suffered a loss of cabin pressure and that all on board died of hypoxia hours before it crashed. Stewart, 42, won 11 PGA Tour events, including three major championships, in his career. He's seen here after winning the 1999 U.S. Open Championship on June 20, 1999. [ + - ]
1995: Tennis player Bobby Riggs, who was the world's top professional player in 1946-47 and gained more fame for his 1973 "Battle of the Sexes" tennis matches against top female players Margaret Court and Billie Jean King, dies of prostate cancer at the age of 77 in Encinitas, California. [ + - ]
1994: Susan Smith of Union, South Carolina, reports to police that a black carjacker had driven off with her two sons. Nine days later, she would confess to letting her 1990 Mazda Proteg������ roll into a nearby lake, drowning her children inside. Smith would be convicted and sentenced to life in prison in July 1995. [ + - ]
1993: Actor Vincent Price, well known for his distinctive voice and his roles in horror movies such as "The Fly," "House of Usher," "The Masque of the Red Death," "Theatre of Blood" and "The Abominable Dr. Phibes," dies of lung cancer at the age of 82 in Los Angeles. [ + - ]
1986: The New York Mets win Game 6 of the World Series in the 10th inning when a routine ground ball goes through Boston Red Sox first baseman Bill Buckner's legs. The Red Sox would lose Game 7 two days later as well and Buckner would soon become the scapegoat for frustrated Boston fans. [ + - ]
1985: Singer Ciara is born under the birth name Ciara Princess Harris in Austin, Texas. Since making her debut in 2004, the R&B singer sold more than seven million albums worldwide and attained eight Billboard Hot 100 top-10 singles, including the No. 1 hit "Goodies" off her debut studio album of the same name. [ + - ]
1984: Pop singer Katy Perry, best known for songs such as "I Kissed a Girl," "California Gurls," "Teenage Dream" and "Firework," is born under the birth name Katheryn Elizabeth Hudson in Santa Barbara, California. [ + - ]
1983: In what's codenamed Operation Urgent Fury, the United States and its Caribbean allies invade Grenada, six days after Prime Minister Maurice Bishop and several of his supporters were executed in a military coup. The invasion resulted in U.S. victory and the restoration of constitutional government in the Caribbean island nation. [ + - ]
1973: The Yom Kippur War, a 20-day war fought between Israel and a coalition of Arab states led by Egypt and Syria, ends with a ceasefire, three days after a United Nations-brokered ceasefire fell apart. The war began on Oct. 6 when Egyptian and Syrian forces crossed ceasefire lines to enter the Israeli-held Sinai Peninsula and Golan Heights respectively, which had been captured and occupied since the 1967 Six-Day War. [ + - ]
1971: Baseball pitcher Pedro Mart������nez, an eight-time All-Star, three-time Cy Young Award winner, and 2004 World Series champion, is born in Manoguayabo, Dominican Republic. Martinez won the American League pitching Triple Crown in 1999, leading the league in wins (23), ERA (2.07) and strikeouts (313). He pitched for the Los Angeles Dodgers, Montreal Expos, Boston Red Sox, New York Mets and Philadelphia Phillies in his 18-season career, retiring after the 2009 season with career totals of 3,153 strikeouts, a 2.93 ERA and a 219-100 win-loss record. [ + - ]
1968: Led Zeppelin makes its performance debut at the University of Surrey in England. Robert Plant and Jimmy Page are seen here in 1973. [ + - ]
1962: Nelson Mandela is sentenced to five years in prison after being found guilty of leading workers to strike in 1961 and leaving South Africa illegally. The following year Mandela and 15 other African National Congress leaders were charged with 221 acts of sabotage designed to "ferment violent revolution." All but one would be found guilty and sentenced to life in prison in June 1964. [ + - ]
1962: During the Cuban Missile Crisis, United States Ambassador to the United Nations Adlai Stevenson shows photos at the U.N. proving Soviet missiles are installed in Cuba. [ + - ]
1962: John Steinbeck, the author of novels such as "The Grapes of Wrath" and "Of Mice and Men," wins the Nobel Prize in Literature for his "realistic and imaginative writing, combining as it does sympathetic humor and keen social perception." [ + - ]
1957: Voice actress Nancy Cartwright, best known for her long-running role as Bart Simpson on the animated TV series "The Simpsons," is born in Dayton, Ohio. [ + - ]
1944: The USS Tang under Richard O'Kane, the top American submarine captain of World War II, is sunk by the ship's own malfunctioning torpedo, which curves around and strikes the ship. A total of 74 men were killed and nine survivors, including O'Kane, were picked up the next morning by a Japanese destroyer. The nine captives would be placed in prison camps until the end of the war. [ + - ]
1941: Singer Helen Reddy, often referred to as the "Queen of '70s Pop," is born in Melbourne, Australia. She enjoyed international success during her career, especially in the United States, where she placed 15 singles in the Top 40 of the Billboard Hot 100, with three of those songs reaching No. 1, including her signature hit "I Am Woman." [ + - ]
1940: Benjamin O. Davis Sr. is named the first black general in the United States Army. [ + - ]
1940: Hall of Fame basketball coach Bobby Knight, who won 902 NCAA Division I men's college basketball games, third all-time to Mike Krzyzewski and Jim Boeheim, is born in Massillon, Ohio. He is most well known as the head coach of the Indiana Hoosiers from 1971 to 2000. He also coached at Texas Tech and at West Point. [ + - ]
1931: The George Washington Bridge spanning the Hudson River between New York City and New Jersey opens to public traffic. [ + - ]
1928: Actress Marion Ross, best known for her role as Marion Cunningham on the television series "Happy Days," is born in Watertown, Minnesota. [ + - ]
1921: Bat Masterson, a figure of the American Old West known as a buffalo hunter, U.S. marshal and Army scout, gambler, frontier lawman and journalist, dies of a heart attack at age 67 in New York City. [ + - ]
1912: Comedian and country singer Minnie Pearl is born under the birth name Sarah Ophelia Colley in Centerville, Tennessee. Pearl appeared at the Grand Ole Opry for more than 50 years and on the television show "Hee Haw," becoming famous for gentle satire of southern and hillbilly culture, wearing a hat with a price tag hanging from it and bellowing her catch phrase "How-w-w-DEE-E-E-E!" She died of complications from a stroke at the age of 83 on March 4, 1996. [ + - ]
1888: Pioneering aviator and explorer Richard Byrd, who would claim that his expeditions had been the first to reach the North Pole and the South Pole by air, is born in Winchester, Virginia. While there is some doubt about his North Pole claim, his South Pole claim is generally supported by a consensus of those who have examined the evidence. He died of a heart ailment at the age of 68 on March 11, 1957. [ + - ]
1881: Painter and sculptor Pablo Picasso, widely hailed as one of the greatest and most influential artists of the 20th century and the creator, with Georges Braque, of Cubism, is born in M������laga, Spain. He died at the age of 91 on April 8, 1973. [ + - ]
1854: The English army suffers heavy losses against Russia in the Battle of Balaclava during the Crimean War. The battle inspired Alfred Lord Tennyson's poem "Charge of the Light Brigade." [ + - ]
1838: Composer Georges Alexandre-Cesar-Leopold Bizet, best remembered for his opera "Carmen," is born in Paris, France. [ + - ]
1825: Composer Johann Strauss II, who composed more than 500 waltzes, polkas, quadrilles and other types of dance music, and is best known for his waltz "The Blue Danube," is born near Vienna, Austria. [ + - ]
1806: Maj. Gen. Henry Knox, a military officer of the Continental Army and later the United States Army who also served as the first U.S. secretary of war, dies at the age of 56 in Thomaston, Massachusetts. Three days earlier he had swallowed a chicken bone, which lodged in throat and became infected. Two forts, one in Kentucky and another in Maine, and Knox Hall at Fort Sill, Oklahoma, home of the U.S. Army Field Artillery School, were named after him. [ + - ]
1415: The army of Henry V of England defeats the numerically superior French army at the Battle of Agincourt in northern France. The battle is the centerpiece of William Shakespeare's play "Henry V," which introduced the famous "St. Crispin's Day Speech" with Henry urging his "band of brothers" to stand together in the forthcoming fight. [ + - ]
1400: Geoffrey Chaucer, best known today for "The Canterbury Tales" and widely considered the greatest English poet of the Middle Ages, is believed to have died at the age of either 56 or 57. Although his tomb is engraved with the Oct. 25 date, the exact date of his death, along with the cause, remains unknown, as the tomb was engraved 100 years after his death. Upon his death, Chaucer became the first poet to be buried in Westminster Abbey. [ + - ]


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Oregon Focus: State Symbols: Seal
About the Oregon state seal
A committee composed of three prominent Oregonians presented the design for the seal to the Constitutional Convention of 1857. The design chosen was submitted by Harvey Gordon (1828-1862), who was by profession a surveyor.
This seal was adopted as the last official act of the territorial legislature in 1857. In 1859, the new state legislature added a thirty-third star to indicate that Oregon was the thirty-third state admitted to the Union. Since the adoption, many versions of the state seal have been issued by various departments and agencies of government. Some included a setting sun and some have the eagle's head turned the opposite way. Because of the resulting confusion about which seal issued was official, Governor Tom McCall, who served as the state's top leader from 1967 to 1975, asked all state departments to follow the bronze seal on the floor of the Capitol rotunda, even though it has a setting sun, which is not included in the official description.
As originally adopted, the seal consists of a shield supported by 33 stars. The words "The Union" are on the banner in the middle. Above the banner are mountains, an elk with branching antlers, a wagon, the Pacific Ocean on which a British man-of-war ship is departing, and an American steamer ship arriving. Below the banner is a sheaf, a plough, and a pick-axe. Above the shield is a crest in the form of an American eagle. The legend surrounding the seal is "State of Oregon" and "1859."
The components of the seal each have symbolic significance. "1859" signifies the date of Oregon's admission into the Union. The 33 stars show that Oregon was the thirty-third state to join the Union. The American eagle at the top denotes the Union of the States -- Peace Through Strength -- depicted by the olive branch and the arrows. The fact that Oregon was never wholly dominated or governed by a foreign power is shown by the British man-of-war ship leaving while the American steamer is arriving.
Suggestions for teachers
Ask students to:
Design a school or class symbol. They can also design their own personal seals.
Discuss the meaning of each the components of the state seal.
Compare the Oregon state seal with seals from other states. What are the similarities and differences?
Draw the state seal.
Print out and color the state seal. (use state seal in coloring book-PDF)


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Ruud recommends keeping back-to-school receipts
Keeping school supply receipts may lead to savings when filing a 2013 Minnesota income tax return, said Sen. Carrie Ruud, R-Breezy Point.
There are two educational tax relief options — a credit and a subtraction — available to help families with students in kindergarten through 12th grade who attend public, private and home school.
The first option is a refundable K-12 education credit that reimburses Minnesota taxpayers for up to 75 percent of their school expenses. The income limit varies. For example, if there are one to two students, the household income must be less than $37,500. If there are three students, the income limit is $39,500. Four students is $41,500.
The second option is the K-12 education subtraction that reduces overall taxable income. There is no income limit.
Qualifying expenses include education services or required materials to assist with a child's education. Examples include paper, pens, notebooks, textbooks, rental or purchases of education equipment such as musical instruments, computer hardware and educational software, after-school tutoring and educational summer camps.
Parents simply need to save their receipts from purchases and apply those expenses to their 2013 Minnesota tax return next year.
For more information on these education tax breaks, visit the Department of Revenue website at www.revenue.state.mn.us or contact the department at 651-296-3781 or 800-652-9094.


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What New Media Has Taught Us About Truth
Mitch Joel | Posted 09.23.2012 | Canada Business
Read More: Instagram, Cognitive Surplus, Mitch Joel, Twitter, Curation, Twist Image, Six Pixels of Separation, Media, Facebook, Clay Shirky, Journalism, Reporting, Here Comes Everybody, Aurora Colorado, Dark Knight Rises, Cnn, Media Education, New Media, Media Hacker, News, Blogging, Canada Business News
Where do we go for the truth... the whole truth and nothing but the truth? In essence, new media is most amazing because people are beginning to doubt what they read, hear and see. There's nothing wrong with that. In fact, it's probably one of the best thing that has happened to the news since it was created.


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UNIVERSITY OF WISCONSIN River Falls
Housing is a major expense for most American households. The US Department of Housing and Urban Development classifies households that spend more than 30 percent of their monthly household income on housing as "cost-burdened" households. When households spend more than 30 percent of their monthly income on housing they are likely to find it challenging to have sufficient income to meet other basic needs (food, clothing, medical care, education, retirement savings, etc.).
Homeownership, while now a somewhat tarnished goal, has long been a part of the "American Dream." Owning a home is often the largest investment a family has and a high level of homeownership is believed to contribute to building stable communities and engaged citizens. It is nearly impossible to pick up a paper or listen to a newscast that doesn't reference the nation's foreclosure crisis. Most economists believe that the sharp drop in home values and the high levels of foreclosures contribute significantly to the weak economic recovery that began in 2008. People's real wealth has fallen, limiting their ability and desire to consume and undermining their faith in their economic future. In short, housing issues are central to many of the most important social, economic and political issues facing the country today.
There is both good and bad news about housing in the St. Croix Valley. On the one hand, home ownership tends to be higher in these counties than in their respective states. On the other, the relatively high price of homes in these counties has contributed to the fact that higher percentages of households in this area are classified as "cost-burdened." In addition, residential foreclosure rates in three of the five counties were greater than their respective state averages during the recent recession.