Hello my lovely readers. Love has been on my mind a lot recently, maybe because Valentine's Day is tomorrow, who knows? So today I thought I would share with you some of my favourite songs about love.
The Beatles- All You Need Is Love. Obvious? Maybe. But it's a classic!
The Eels- Beautiful Freak. I love how weirdly beautiful song is. If you just read the title you may find it a little insulting but the song is about accepting the weirdness of someone and loving them because of it rather than in spite of it. My favourite line is, "some people think that you have a problem but that problem lies only with them".
Alanis Morissette- You Owe Me Nothing In Return.
The Pogues- I Love You 'Till The End.
The Hollies- The Air That I Breathe.
Peter Gabriel- In Your Eyes. On the surface In Your Eyes seems like a typical love song (apart from the fact that it's Peter Gabriel and nothing PG does sounds typical) but if you listen to the lyrics you hear that it's saying that love is hard. In Your Eyes makes it clear that love is not always perfect but it's worth the fight. My Favourite line is "when I want to run away I drive off in my car. But whichever way I go I come back to the place you are".
Lord Huron- Fool For Love.
Bryan Ferry- Is Your Love Strong Enough?
David Bowie- Wild Is The Wind. David Bowie has made so many wonderful songs and this one is so beautiful. My favourite line is "you touch me I hear the sound of mandolins. You kiss me with your kiss my life begins."
So there are 10 of my favourite love songs I hope you enjoyed reading and maybe found a song that you want to check out.
Do you like any of these songs? What are your favourite love songs?


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Q: Find the number of homomorphisms between $\mathbb{Z}_m$ and $\mathbb{Z}_n$ Although there are many attempts to the problem but I wasn't really able to understand those so I took some idea from examples and attempted it. Can someone just go through it please.
My attempt: Let $\sigma:\mathbb{Z}_{m}\to \mathbb{Z}_{n}$. The kernel $\ker(\sigma)$ is a normal subgroup of $\mathbb{Z}_{m}$. So $\ker(\sigma)=\langle\frac{m}{d}\rangle$, where $d|m$. Now $\operatorname{im}(\sigma$) is a subgroup of $\mathbb{Z}_n$. So, now the order of the image should be $d$ so $d|n$. Now the number of homomorphisms when the kernel is of order $d$ will be $\sum_{d|m,d|n}\varphi(d)$. From here we can conclude that the no of homomorphisms should be $\gcd(m,n)$. Is this OK? Where am I making mistakes?

A: Yes, there are $\gcd(m,n)$ such homomorphisms.
Another way to see it is that we need $f([1])=[a]$ where $0\le a<n$ and that
$m[a]=[ma]=0$ in $\Bbb Z_n$, that is, $n\mid ma$ or $ma\equiv 0\pmod n$.
The solution to this congruence is $a\equiv 0\pmod{n/g}$ where
$g=\gcd(m,n)$, so that $a=jn/g$
for $0\le j<g$, so there are $g$ solutions.

A: There is an article on the same topic, of which I have a photocopy, in an old issue (sorry, don't have the date) of either American Mathematical Monthly or Mathematics Magazine (I cannot tell from my copy), authors Joseph A Gallian and James Van Buskirk.  They give the number of group homomorphisms as $\gcd(m,n)$.  Your analysis is close, except you formulated the sum incorrectly; the correct sum is over the set of divisors of the $\gcd$.  [They also give the corresponding number of ring homomorphisms.]

A: A homomorphism $\sigma:\mathbb Z_m\to\mathbb Z_n$ is uniquely determined by $\sigma(1)=a\in\mathbb Z_n$. This has to be such that $ma=\sigma(m)=0$, so that $a\gcd(m,n)=0$. Thus, there are $\gcd(m,n)$ such homomorphisms.

redpajama_set_name: RedPajamaStackExchange


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Monthly Archive for May, 2007
: May, 2007
Easy money for college!
By mysa-admin	on May 31, 2007 at 5:29 PM
I watch MTV on the treadmill most mornings, and could they please stop playing the same five videos over and over again? Does anyone really like Chris Daughtry? No, but seriously, I'm also getting a …
Somerset looking to boost teacher attendance
By mysa-admin	on May 30, 2007 at 11:17 AM
The Somerset Independent School District is getting creative to boost teacher attendance. Starting next school year, administrators will reward one teacher from each of the district's six campuses …
Harlandale film students clinch Emmy
Harlandale High School's film students have done it again &#151 they've produced Emmy Award-winning work. School district officials sent out a press release on Friday announcing the film program's …
Consolidations on hold in SAISD
So here's the latest on school consolidations in the San Antonio Independent School District: There won't be any next year. "It's just too late in the school year," Superintendent Robert …
State releases TAKS results
The Texas Education Agency just released preliminary results of the Texas Assessment of Knowledge and Skills, which students in grades 3-11 took this spring. Agency officials have posted a press …
Sam Houston in the clear?
Sam Houston High School may be in the clear, if preliminary state test results don't change much. The East Side school, in the San Antonio Independent School District, has worked its tail off this …
SAISD school consolidation
Talk of school consolidation in the San Antonio Independent School District hasn't gone away. Superintendent Robert Dur&oacuten is expected to pitch his recommendation about which campuses to …
Education writers gather in Los Angeles
By mysa-admin	on May 7, 2007 at 4:12 PM
Last week, I joined education reporters from across the country in Los Angeles for the Education Writers Association's national conference. Covering San Antonio's South Side school districts, it's …
WellMed's COVID-19 vaccination hotline reopening, more doses coming to San Antonio

redpajama_set_name: RedPajamaCommonCrawl


I was in my sophomore year of high school in El Paso, TX. We heard about it at the beginning of school that day, and all of the teachers quickly turned on the TV. We were all in a trance, and it felt so surreal. We switched from class to class as usual, but each teacher had the TV on so we could watch what was happening. They didn't bother with classwork that day, and we all shuffled through the day in a daze. I remember some of my classmates being frightened for relatives or friends that were in New York, and the rest of us trying to comfort them.
El Paso has a huge military base, and at some point we all got scared that the terrorists would target that base. Many of my classmates were military children, but I don't think any of us quite realized the way this attack would affect our relatives and friends who were part of the armed forces.
It's hard to believe it has already been a decade since that fateful day. I was working at Scott's high school this past Friday, and the teacher asked the freshmen what they remembered about Sept. 11. The main response was, "My mom came and picked me up from preschool!" It makes me wonder what event will mark that generation like September 11 did for us.
Let's take some time today to remember those who passed and to celebrate the amazing American spirit that burst forth that day.
To those who work each and every day to protest our freedom, THANK YOU.


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pce powder_The latest Qatar News,Qatar Technology,Qatar Indus
When the same polycarboxylic acid sloughing agent is used but different cement is used, it is possible that this polycarboxylic acid sloughing agent has good compatibility with one kind of cement but poor compatibility with another cement, and when u Polycarboxylate superplasticizer is the third generation of high performance superplasticizer after common superplasticizer and superplasticizer. Because the steric hindrance of the extended polymer side chain effectively hinders the secondary agglomeration between cement particles, so the product has high dispersion performance and can maintain this performance for a long time to realize the Polycarboxylate superplasticizer has more advantages than traditional naphthalene and aliphatic superplasticizer in mixing high strength grade concrete, but its advantages of high water reduction cannot be brought into full play when the strength is Natural river sand has been exhausted after decades of large-scale mining, concrete production enterprises began to use machine-made sand as fine aggregate on a large scale. If the compatibility of polycarboxylate superplasticizer and cement is not good, the concrete mixture is prone to some problems, such as segregation, bleeding, greater slump loss, shorter setting time and so on, so that the concrete mixture can not b The wide application of mineral admixtures mainly derived from industrial solid wastes diversifies the composition of cementitious materials, which is one of the main characteristics of modern concrete. Adding polycarboxylate superplasticizer can make the compressive strength of precast concrete reach 40MPa grade at 8h to 18h. The impermeability of concrete is related to its porosity and pore structure. Polycarboxylate superplasticizer is based on unsaturated polymerizable monomers with active groups such as carboxyl group, sulfonic acid group, hydroxyl group and polyoxene group as raw materials.
Compatibility between polycarboxylic acid slump protection agent and various raw materials of concrete
When the same polycarboxylic acid sloughing agent is used but different cement is used, it is possible that this polycarboxylic acid sloughing agent has good compatibility with one kind of cement but poor compatibility with another cement, and when u…
Deterioration of superplasticizer
Polycarboxylate superplasticizer is the third generation of high performance superplasticizer after common superplasticizer and superplasticizer.…
What is the advantage of polycarboxylate superplasticizer?
Because the steric hindrance of the extended polymer side chain effectively hinders the secondary agglomeration between cement particles, so the product has high dispersion performance and can maintain this performance for a long time to realize the…
What should be paid attention to when using polycarboxylate superplasticizer for C30 and below concrete?
Polycarboxylate superplasticizer has more advantages than traditional naphthalene and aliphatic superplasticizer in mixing high strength grade concrete, but its advantages of high water reduction cannot be brought into full play when the strength is…
Effect of Limestone Powder in Machine-made Sand on PCE powder
Natural river sand has been exhausted after decades of large-scale mining, concrete production enterprises began to use machine-made sand as fine aggregate on a large scale.…
Effect of cement temperature on the performance of pce powder
If the compatibility of polycarboxylate superplasticizer and cement is not good, the concrete mixture is prone to some problems, such as segregation, bleeding, greater slump loss, shorter setting time and so on, so that the concrete mixture can not b…
Why is polycarboxylate superplasticizer more suitable for modern concrete?
The wide application of mineral admixtures mainly derived from industrial solid wastes diversifies the composition of cementitious materials, which is one of the main characteristics of modern concrete.…
How to use polycarboxylate superplasticizer for different kinds of concrete?
Adding polycarboxylate superplasticizer can make the compressive strength of precast concrete reach 40MPa grade at 8h to 18h.…
Effect of polycarboxylate superplasticizer on the concrete properties
The impermeability of concrete is related to its porosity and pore structure.…
Polycarboxylate superplasticizer advantages
Polycarboxylate superplasticizer is based on unsaturated polymerizable monomers with active groups such as carboxyl group, sulfonic acid group, hydroxyl group and polyoxene group as raw materials.…
Development of polycarboxylate superplasticizer
According to the different molecular structure, it can be divided into four generations of polycarboxylate series superplasticizer, the first generation is acrylic acid copolymer, the second generation is propylene ether type, the third generation is…
Problems when using pce powder
In terms of action mechanism, the molecular structure of polycarboxylate superplasticizer is comb type, and the polar anion…
Mobile phone parts market demand trends and where can I buy the high-quality iphone 7 plus battery replacement
Does iPhone 13 have fingerprint unlock under the screen? According to the news, the design of the iPhone has basically been completed, but the previously rumored fingerprint unlocking under the screen will not appear on the iPhone 13. However, accord…
What are the advantages and disadvantages of lithium batteries?
Calcium Dodecyl Stearate
WC powder
Nickel Oxide NiO
Bi2S3 powder
Prestressed Concrete
Cu-Ni alloy powder
Indium Tin Oxide ITO Powder
foamed concrete
Tantalum Silicide
Foam Lightweight


Freudenberg is a small medieval town situated in Germany. The historical white and black half-timbered houses are the most beautiful I've ever seen. It was a perfect destination away from the noise from the big cities.
Downtown Dubai, along Sheikh Zayed Road. Downtown Dubai, is a large-scale complex. It is the home of some of the city's most important landmarks including Burj Khalifa, Dubai Mall, and Dubai Fountain.
Ouro Preto (Black Gold) is a city in the state of Minas Gerais, Brazil, a former colonial mining town located in the Serra do Espinhaço mountains and designated a World Heritage Site by UNESCO because of its outstanding Baroque architecture.
Reykjavík is the capital and largest city of Iceland. It is located in southwestern Iceland, on the southern shore of the Faxaflói Bay.


Dutch names are used in the Netherlands and Flanders. See also about Dutch names.
Derived from the given name Aaij, a short form of ADRIAAN and other names.
Derived from Old Dutch ekster "magpie".
Originally denoted a person who came from an uncertain place called Aaldenberg, meaning "old mountain".
Means "son of Aalf", a short form of ADOLF.
Means "son of Aalmar", a Dutch form of ADELMAR.
From Dutch aarden meaning "clay, stone, earth". It probably denoted a person who worked with those materials.
Denoted a person who hailed from a place of this name in the Netherlands, or from Arlon in Belgium (which is Aarlen in Dutch).
From various Dutch places meaning "ABBE's farm".
Patronymic surname derived from ABEL or a diminutive of ALBERT.
Means "son of ABE (2)".
Derived from the given name ABRAHAM.
From Abtspoel, the name of an estate near Oegstgeest in South Holland, meaning "abbot's pool".
From the name of various places in the Netherlands and Germany, for example the village of achterberg in Utrecht. The place names are derived from Low German achter "behind" and berg "mountain, hill".
From the name of various places in the Netherlands, derived from Low German achter "behind" and kamp "field".
Denoted a person from various towns in the Netherlands called Achthoven, which is derived from Dutch acht "eight" and hoven "gardens".
Means "son of Addik", a diminutive of ADDE.
From the name of an estate and castle (demolished in 1812) that was formerly in North Holland, the Netherlands. It means "Adrik's home".
Originally denoted a person from the town of Akkersdijk, near Delft in the Netherlands. It means "field by the dyke" in Dutch.
Derived from the given name ALBERT.
Means "ALBERT's farm" in Dutch.
From the name of various streets in the Netherlands.
Possibly from an unknown place name meaning "old field" in Dutch.
From Dutch allerliefste meaning "most dearest". This name could have referred to the nature of the person or perhaps a phrase the person commonly used.
Means "Aldert's courtyard" from the given name ALDERT combined with Dutch hof "garden, courtyard".
Means "ALFHARD's farm" in Dutch.
From the given name ALFONS.
Means "ALE (2)'s farm" in Dutch.
From the name of a town in the Netherlands, possibly meaning "close, near" in Dutch.
Means "ALTE (2)'s farm" in Dutch.
Means "AMSE's farm" in Dutch.
From the Latin given name ANANIAS.
From the given name ANDREAS.
Derived from the given name ANDRIES.
Means "ANDRIES's farm" in Dutch.
Referred to person who lived at the end of the road or the village, derived from Dutch an gen ent meaning "at the end".
Originally denoted a person from Anholt in the Netherlands, which means "hold, rest" in Dutch (a place where people could rest for the night).
Metonymic surname for a sailor, meaning "anchor" in Dutch, Danish and Norwegian.
From Dutch aan 't veldink meaning "next to the little field".
Derived from the given name ANTONIS or ANTONIUS.
Derived from the given name ANTONIUS.
From the name of a city in the Netherlands, meaning "apple tree" in Dutch.
Indicated a person who lived by or at an apple garden, from Dutch appel "apple" and hof "garden, courtyard".
Indicated a person who was from a farm called Aperloo, probably a derivative of appel meaning "apple".
From Dutch arbeid meaning "work".
From Dutch arbeider meaning "worker".
Denoted a person from Arendonk, a town between in northern Belgium. It is derived from arend "eagle" and donk "hill".
Means "son of ARIS (2)".
Means "doctor, physician" in German, ultimately from Latin archiater.
Means "son of Aske", a diminutive of ASSE.
Denoted a person from Assel, Asselt or Hasselt, the name of communities in the Netherlands and Belgium. They derive from Germanic asc "ash tree" and lauha "woods on sandy soil", or hasal "hazel tree".
From Dutch es meaning "ash tree" (plural essen) and berg meaning "mountain".
From the name of a place called Assendorp, composed of Dutch essen and dorp, meaning "ash tree village".
From a place name meaning "ASSE's farm".
From a place name, possibly from a dialectal variation of Dutch over meaning "over" combined with esch meaning "ash tree".
From a place name meaning "the edge of camp" in Dutch.
Means "son of Baaij", the given name Baaij being a diminutive of names like BAUGULF, BOUDEWIJN or BERNARD.
From the given name BAAK.
From the name of a town in the Netherlands, possibly from Baard, a variant of BERT, and wijk meaning "neighbourhood, district".
Indicated a person coming from the town of Beers in the Netherlands.
Means "beard" in Dutch, originally describing a person who wore a beard.
Means "boss, overseer" in Dutch.
Means "bakery" from Dutch bak "bake" and huis "house", an occupational name for a baker.
Dutch cognate of BAKER, from Middle Dutch backer.
From a Germanic word meaning "mountain".
From the given name BERNARD.
Possibly a Dutch form of BAUMER or BÖHMER.
From Dutch zuid "south" and hout "forest". It refers to the south of the forest in The Hague.
Possibly an adaptation of French beurre fin meaning "good butter".
From a nickname derived from Dutch borst "chest".
Derived from Middle Dutch bosch meaning "wood, forest".
From the Low German given name BODE.
Means "architect, builder" in Dutch.
Derived from the given name BRAM.
From the given name BOELE.
Originally indicated a person from the Dutch town of Bunschoten, which might mean "raised, enclosed land".
Originally indicated a person who lived in a valley, from Dutch dal meaning "dale, valley" and man meaning "man".
Means "dike, dam" in Dutch and Danish. In modern Danish it also means "pond".
From Dutch groot meaning "big, great".
From Middle Dutch haven meaning "harbour, haven".
From Dutch klerk meaning "clerk", making this a cognate of CLARK.
Variant of VAN DER VEEN.
Means "the Frisian" in Dutch, referring to a person from Friesland.
Means "the white" in Dutch, a nickname for a person with white hair.
From the given name DRIES.
Means "oak tree", from Dutch eik "oak" and boom "tree".
Probably from a place name which was a derivative of Dutch els meaning "alder tree".
Derived from the given name Erk, a variant of ERIK.
Name for a person from Franconia in Germany, so called because it was settled by the Frankish people.
Derived from the given name Geel, itself from GILLIS or GILBERT.
German and Dutch cognate of GLASS.
From the Germanic given name GOZZO.
Occupational name meaning "pedlar" in Dutch.
Originally indicated a person from Haanrade, a small village in the south of the province of Limburg in the Netherlands.
From Old Norse hagi or Old Dutch hago meaning "enclosure, pasture".
From Dutch heer "lord, master", a nickname for a person who acted like a lord or who worked for a lord.
Patronymic from a diminutive of the given name HENDRIK.
Derived from the given name HENDRIK.
Derived from the given name HENDRIK. A famous bearer was the American rock musician Jimi Hendrix (1942-1970).
From the given name HERMAN.
Occupational name for a hat maker, from Dutch hoed "hat" and maker "maker".
From Dutch hoek meaning "corner".
Indicated a person from the Dutch province of HOLLAND (1).
Originally referred to a person from the region of HOLSTEIN between Germany and Denmark. A famous bearer of this name was the English composer Gustav Holst (1874-1934).
From Old English, Old Dutch and Old Norse holt meaning "forest".
Derived from the given name HUBERT.
Possibly an Americanized form of HOEK.
Means "buyer of wood" in Dutch.
Derived from the given name HUMBERT.
Nickname for a busy person, from Middle Low German and Middle Dutch hommel, Middle High German hummel, all meaning "bee".
Derived from the given name JACOB.
Means "son of JAN (1)".
From the Dutch title jonkheer meaning "young lord". It was originally a medieval noble designation (not an actual title) for a young nobleman.
Derived from the given name JOOST.
Name for a person who lived near or worked at a chapel, ultimately from Late Latin cappella, a diminutive of cappa "cape", arising from the holy relic of the torn cape of Saint Martin, which was kept in small churches.
Derived from Dutch kikker meaning "frog".
Means "small, little" from German klein or Yiddish kleyn. A famous bearer of this name is clothes designer Calvin Klein (1942-).
Possibly from Middle Dutch cloet meaning "lump, ball". In some cases this was a nickname for an oafish person. In other cases it may have been a name for someone who lived near a sign which had a globe on it.
Derived from the given name NICOLAAS.
Occupational name meaning "merchant" in Dutch.
Means "cooper, barrel maker" in Dutch.
From the name of a small town in the province of Utrecht, Holland, derived from lang means "wide" and broek means "meadow".
From various place names meaning "long mountain" in German and Dutch.
From the given name LAURENS.


A half hourly bus runs from directly outside to and from the famous 'Lobster Pots' lift in Peisey. We also offer a minibus shuttle (8-10 mins) direct to the slopes in Vallandry between 08.30 and 09.30, with collection after 16.30 from the piste side bar.
From the pistes of Vallandry you can gain access to the large resorts of Les Arcs and La Plagne and their 425 kms of piste. The off piste skiing is equally phenomenal and enables good skiers to slide right back to the doorstep from both sides of the Paradiski area.
Peisey Vallandry resort is made up of a collection of small quaint villages nestled in a pretty valley between Les Arcs and La Plagne – a perfect location to base yourself for exploring the huge Paradiski. Upspoilt by over development often found in many French resorts, the cows still live in the barns during winter and are set to pasture in the summer to create the fantastic local Beaufort cheese.
Purchasing a 6 or 7 day Les Arcs liftpass allows access to La Plagne for one day of the week (all week access passses also available), and a free half day of skiing on your day of arrival.


Last January, when I packed up my car to move to Arizona, not everything could come. My attachment to places and things, along with connections to people, all needed to be sorted through.
I had to be willing to let go, big, to fly the trapeze. I had to have the willingness to experience the in-between, when I'd be in the air, where I was most afraid. Without letting go, however, I'd only recreate the life I had in Delaware in a new location. I needed to, was ready to, move and fly!
What do you keep holding onto that holds you back?
Think of the resolutions and changes you want this year. In order to get there, you need to let go of what has been. After all, you no longer want it any more, do you?
REMEMBER, no one flies the trapeze alone, trapeze artists don't. So ask yourself, "What do I need so I can let go, so I can have the life I really want and need?" Now, consider me your trapeze partner. I'm here to assist you in getting to where you want to be!
Are you ready to start? It's time for us to talk! Your complimentary, 30-minute telephone Discovery Session is waiting for you!
Unfortunately, there's the perception that wealth, in any form, comes from the outside, having little to do with your health and well being. But it is incorrect.
Living your life from the inside out, is what gives you access to what is really needed, to do what you're here on this planet to do and be.
Wellth depends upon you, making you the priority. Having routines and activities that support, enhance, and nourish your wellness are key, and it doesn't work if you leave it up to chance or at the end of your To Do list.
During the last 6 weeks or more, I changed my morning routine, immediately starting my day attending to work related issues. Then, last week, I smacked into a wall. I hadn't eaten all day and I was UBER multitasking, which led me to becoming extremely overwhelmed. As fear continued to grow, I physically felt it, something I never experienced before. Quickly, I reached out to a friend who helped me tremendously.
Looking back at my perfect storm, I realized one huge contributing factor was continuing to hop out of bed and going to work almost immediately, without taking care of me. I no longer had reserves to tap into as I tapped out.
Since then, I've been making changes. I can't go at things the way I have and build my wellth, which I rely upon to finance, so to speak, my work and my life. I'm making my health and wellness, me, my priority and I'm noticing the difference.
If you realize changes are needed to increase your wellth but aren't sure what to do or where to start, let's talk. You can start the process right now by clicking on this link, go to the Discovery Session icon, click on it, and schedule your free 30-minute phone consultation.
Do you have the courage and daring you need?
Thank you for downloading the S.H.I.N.E. analysis. I hope you found it helpful in clarifying what you need to change your life, thoughts, and/or behavior so you can truly SHINE!
Becoming clear about what you need, want, or desire, as well as identifying the hurdles, is crucial as you contemplate change. Without knowing where you are right now, you can't navigate to someplace else.
It's important to understand that making changes on your own can be very challenging without the right support. After all, if you could have made these changes, you would have. Many people think all they have to do is 'pull yourself up by your bootstraps'. Before owning my own pair of cowboy boots, I thought (like most people) it meant doing it all alone, without any help. I was wrong! Bootstraps are built into the boot to assist the wearer in putting them on each time.
So why am I talking to you about bootstraps?
The S.H.I.N.E. analysis is a tool and you may need some guidance and support in completing, using, and implementing it. You don't have to, nor should you, go it alone. Like those bootstraps, I can be of assistance to you, which is why I'm offering you a complimentary, 30-minute, personal phone consultation to go over your S.H.I.N.E. analysis.
It's simple and easy to schedule and you can do it right now. Click on this link www.BethKeil.com, and then click on the Discovery Session icon which will take you directly to an online scheduler. Choose a date and time that is most convenient for you.
I look forward to us speaking very soon!
Everyone is tattooed --- what do yours say about you?
Each of us has a tattoo, actually several. Some are inked while others aren't so visible. These unseen tattoos are how we feel about, and judge, ourselves. Hiding them from others comes from fearing that if you were really, truly seen, others will judge you. So instead, you cover up those tattoos, and work hard pretending you're fine. Pretending, however, leads to feelings of shame, and shame grows in silence, secrecy, and judgment.
You might be thinking---Thanks, Beth. This New Year has just begun, and now this?
Are you ready to shed the tattoos you no longer need or want?
Ask--- if one of your best friend or child were to do any of the above would you call them any of those names?
Would you let anyone call one of your best friends or child one of those words?
Now begin treating yourself like you do them.
Step 3: Redesign your tattoo!
People with inked tattoos they no longer like (think before you ink!) can have them removed or have a tattoo artist create another tattoo, transforming the previous design into something beautiful.
Ask yourself what you really want your tattoo to say about you and write it down right now! That's right, right now! You now get to choose what you want it to say and how you want to feel about yourself.
Would you like support in updating your tattoos? Be amongst the growing number of people who are joining me for the upcoming virtual seminar Visioning Your 2018: Tapping into Your Inner Wisdom on Saturday, January 20, 2018. Click here to learn more.
Do you need a more personalized conversation about Visioning Your 2018? Let's both jump on a call asap so I can answer your questions! I have room for 5 conversations. Click here and grab yours now!
Here's to inking your New Year!
New Year - Resolutions or Results?
As a result of waiting, how much extra weight do you now have to lose? What has been the impact on your health and well-being by continuing to smoke, be stressed, worried and anxious? How happy are you, continuing to carry these issues with you year after year?
Are you ready to make 2018 your result year?
In the spirit of this New Year being your result year, please join me for Visioning Your 2018: Tapping into Your Inner Wisdom, a FREE 1-hour teleseminar that will assist you in gaining more clarity about what you need and want in this coming year!
After you pre-register, you will receive a confirmation email with all the information you need to jump on the call. A few days before the seminar you'll receive an email reminder, along with handouts so you can follow along while we are on the phone together.
Here's to 2018, your year for amazing breakthrough and results!


This DPI map shows the highest and lowest 3-year dropout rates by district.
Districts in the northeast and southeast had the highest dropout rates, as well as the highest rates of short-term suspensions, or suspensions lasting 10 days or less. DPI researcher Kenneth Gattis says suspensions may be one factor in dropouts that are within a school's control.
"Suspension is a school decision," he told the State Board of Education at Thursday's meeting. "And there has been a correlation for a number of years with dropout."
The map from the DPI report shows the highest and lowest 3-year suspension rates by district.
Statewide suspension rates also rose for the first time in seven years. As in previous years, black students received the most suspensions. In 2014 schools suspended 118,105 black students. White students received 54,812 suspensions, the second-highest number among racial groups.
Black students' short-term suspension rate was triple that of white students. American Indian students' rate was two and a half times greater.
Former teacher and State Board of Education advisor James Ford had questions about the disparities at Thursday's state board meeting.
"Why are we still experiencing such racialized gaps in the short-term and long-term suspensions?" Ford asked. "Even as we are trending down, we haven't closed those gaps."
State Superintendent June Atkinson says North Carolina's relatively inexperienced teacher population is one reason for the racial gap.
"They need extra help and assistance to deal with cultural diversity--to be able to use better classroom management, discipline, positive discipline."
Board members say they plan to hold a deeper discussion about the disparities in the coming months.
A graph from the 2014-2015 DPI report on suspensions, crime and dropouts shows black students received a disproportionate amount of suspensions.
The school crime rate rose last school year by 1.5 percent—the first increase in five years. Rates of crime are distributed relatively evenly across the state. The most common offenses were having a controlled substance and having a weapon, other than a firearm.
Incidents of corporal punishment, or paddling, rose about 20 percent last school year to 147 students, 80 of whom were American Indian. The paddling took place in four counties: Robeson, Graham, Swain and Macon. Robeson and Graham accounted for 92 percent of the paddling incidents. Both have high populations of American Indian students.


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Cambodia Establishes New Fintech Association
August 18, 2018 @ 9:56 pm By Samantha Hurst
The Cambodia Fintech Association (CFA) announced its official launch on Wednesday. The organization revealed it is focused on the country's fintech community, which are fintech startups, accelerators and VCs. According to its website, the CFA is on a mission to become the national, not-for-profit organization to run for the benefit of its fintech members across all corners of Cambodia.
"We aspire to build Cambodia into the leading Indochine country for Fintech Innovation and Investment in the region. We target to achieve this by collaborating with stakeholders to create the best possible regulatory environment, and by fostering an ecosystem of supportive partners and networks so Fintech companies can thrive and grow in Cambodia."
Cambodia Fintech Association also reported it undertakes four major streams of work on behalf of its members, which are the following:
Champion: Advise government and regulators on policy change that supports Fintech innovation and growth
Assist: Provide research, legal/regulatory help, service provider discounts and other benefits that help our members build and scale their Startups
Match: Get customers to buy, investors to invest, and talent to get involved in Fintech solutions
Bridging: Connect ventures (capital), talents (education) and other stakeholders within the Cambodia Fintech ecosystem and provide connections to overseas hubs through our network Events and Partners
According to the Phnom Penh Post, CFA Vice President, Eddie Lee, stated that Cambodia is currently progressing in its fintech, but startups are slowly starting to surface in the country. Lee also explained that CFA has also signed a Memorandum of Understanding with the Taiwan Fintech Association, Thailand Fintech Association and Singapore Fintech Association to establish bridges with similar groups in the region. He added that the next step is to register the CFA with the Asian Fintech Network
This entry was posted in Asia, Fintech and tagged asia, cambodia, cya, fintech, the cambodia fintech association. Bookmark the permalink.


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Ig Nobel winner: Using pork to stop nosebleeds
By MARK PRATT, Associated Press | Posted - Sept. 19, 2014 at 2:31 p.m.
BOSTON (AP) — There's some truth to the effectiveness of folk remedies and old wives' tales when it comes to serious medical issues, according to findings by a team from Detroit Medical Center.
Dr. Sonal Saraiya and her colleagues in Michigan found that packing strips of cured pork in the nose of a child who suffers from uncontrollable, life-threatening nosebleeds can stop the hemorrhaging, a discovery that won them a 2014 Ig Nobel prize, the annual award for sometimes inane, yet often surprisingly practical, scientific discoveries.
This year's winners honored Thursday at Harvard University by the Annals of Improbable Research magazine included a team of researchers who wondered if owning a cat was bad for your mental health; Japanese scientists who tested whether banana peels are really as slippery as cartoons would have us believe; and Norwegian biologists who tested whether reindeer on the Arctic archipelago of Svalbard were frightened by humans dressed to resemble polar bears.
As has become the custom, real Nobel laureates handed out the prizes and winners were given a maximum of 60 seconds to deliver their acceptance speech,
Sticking pork products up the patient's nose was a treatment of last resort when conventional treatments had failed, Saraiya said, and was only used for a very specific condition known as Glanzmann thrombasthenia, a rare condition in which blood does not properly clot.
"We had to do some out-of-the-box thinking," she said. "So that's where we put our heads together and thought to the olden days and what they used to do."
The 4-year-old child's nostrils were packed with cured pork twice, and according to their study, "the nasal vaults successfully stopped nasal hemorrhage promptly (and) effectively."
What are the Ig Nobel prizes?
The Ig Nobel Prizes are a parody of the Nobel Prizes and are given each year in early October for ten unusual or trivial achievements in scientific research. The stated aim of the prizes is to "honor achievements that first make people laugh, and then make them think." The awards are sometimes veiled criticism (or gentle satire), but are also used to point out that even the most absurd-sounding avenues of research can yield useful knowledge.
Organized by the scientific humor magazine Annals of Improbable Research (AIR), they are presented by a group that includes Nobel Laureates at a ceremony at Harvard University's Sanders Theater, and they are followed by a set of public lectures by the winners at MIT.
The method worked because "there are some clotting factors in the pork ... and the high level of salt will pull in a lot of fluid from the nose," she said.
Still, Soraiya does not recommend sticking pork up your nose for a routine nosebleed, as it could cause infection.
Kiyoshi Mabuchi, a professor of biomedical engineering at Kitasato University in Japan, studied the slipperiness of banana peels as an extension of his research into human joint lubrication system.
"I have gotten ... evidence that the friction under banana peels is sufficiently low to make us slip," Mabuchi said via email.
The other good thing about his study is that his colleagues got to eat the bananas.
Several scientists won for studying the mental health of cat owners. The bottom line? Owning a cat may be hazardous to your health.
Dr. David Hanauer, of the department of pediatrics at the University of Michigan and co-author of one of the studies, says there's no reason for cat owners to panic.
"It may simply be that people with depression gets cats because they feel depressed," he said. "I am in no way telling people to get rid of their cats."
Professor Kang Lee at the University of Toronto in Canada was part of a team that won for studying the reactions of people who see human faces in slices of toast. Although the title of the study was called "Seeing Jesus in Toast," no actual images of Jesus were shown. But the study found that in people who merely think they see a face in a slice of toast — or in any other unusual object — the part of the brain involved in facial recognition lights up.
Although his research has legitimate scientific value, he said he's thrilled to win an Ig Nobel.
Online: 2014 Ig Nobels, http://www.improbable.com/ig/2014
Page Two: Science & Tech
Winners of 2013 Ig Nobel awards for weird science
Most recent Science stories
ScienceU.S.
MARK PRATT
The Doomsday Clock reveals how close we are to total annihilation
Utah plans to sue social media companies for alleged harms to children, teens


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Justia Patents US Patent Application for Anti-obesity compositions Patent Application (Application #20060135471)
Anti-obesity compositions
The present invention relates to compositions and methods for treating obesity. More particularly, the invention relates to a composition comprising a lipase inhibitor such as orlistat, and glucomannan such as konjac as well as methods for utilizing such compositions and kits for carrying out this method.
PRIORITY TO RELATED APPLICATIONS
This application is a continuation of U.S. application Ser. No. 10/421,111, filed Apr. 23, 2003, now pending; which claims the benefit of European Application No. 02009254.0, filed Apr. 26, 2002. The entire contents of the above-identified applications are hereby incorporated by reference.
The field of this invention is the field of combating obesity utilizing compositions containing lipase inhibitors.
Adverse effects which occasionally are observed in patients treated with lipase inhibitors are anal leakage of oil (oily spotting) and fecal incontinence. Oily spotting results from physical separation of some of the ingested but unabsorbed dietary fat from the bulk of the fecal mass in the colon.
In U.S. Pat. No. 5,447,953 it has been shown that by combining a lipase inhibitor with substantial amounts of water insoluble crude fibers, the inhibiting effect on fat absorption can be increased. International Patent Application WO 00/09123 demonstrates that by combining a lipase inhibitor such as orlistat with low amounts of chitosan or a derivative or a salt thereof, the phenomenon of anal leakage of oil can be strongly reduced. Various approaches to control oily leakage have been discussed. Among such strategies are i) use of a surfactant to stabilize the oil/water interface in order to prevent coalescence of the oil emulsion in the colon, ii) enhancing water viscosity in the colon to reduce both intensity and frequency of droplet-droplet interactions and by that reducing the probability of coalescence, iii) physical absorption of oil by a lipophilic compound, or iv) increasing the natural stool mass by facilitating bacterial growth in the colon.
The present invention relates to pharmaceutical compositions and methods for preventing and treating obesity. More particularly, the invention relates to a composition comprising a lipase inhibitor, preferably a compound of formula I (orlistat),
and glucomannan, optionally containing one or more pharmaceutically acceptable excipients.
The invention also relates to the compositions as described above for use in the treatment and prevention of obesity and to a process for preparing a composition as described above, comprising mixing a lipase inhibitor with glucomannan and optionally one or more pharmaceutically acceptable excipients.
The invention also refers to a kit for treatment of obesity, said kit comprising a) a first component which is a lipase inhibitor and b) a second component which is glucomannan as defined above, e.g. in an oral unit dosage form, preferably comprising a) from 1 to 100 doses units of orlistat and b) from 1 to 100 doses units of a glucomannan.
Another embodiment of the present invention refers to a kit for treatment of obesity, said kit comprising a) a first component which is a lipase inhibitor and b) a second component which is glucomannan in oral unit dosage forms.
The present invention also relates to the use of a composition as defined above in the manufacture of medicaments useful for the treatment and prevention of obesity and to the use of a lipase inhibitor as defined above in the manufacture of a medicament for the treatment and prevention of obesity in a patient who is also receiving treatment with glucomannan as defined above. This use of glucomannan and lipase inhibitor refers to the simultaneous, separate or sequential use for the treatment and prevention of obesity.
Further the invention is directed to a method of treatment of obesity in a human in need of such treatment which comprises administration to the human of a therapeutically effective amount of a lipase inhibitor and a therapeutically effective amount of glucomannan as defined above. The method refers to the simultaneous, separate or sequential administration of the compounds. A further embodiment of the present invention is a lipase inhibitor and glucomannan or konjac as defined above as a combined preparation for simultaneous, separate or sequential use for the treatment and prevention of obesity. The invention also refers to the use of glucomannan or konjac as defined above in the manufacture of medicaments useful for the treatment and prevention of gastrointestinal side effects selected from the group of oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence and to a method of treatment or prevention of gastro-intestinal side effects selected from the group of oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence in a human in need of such treatment which comprises administration to the human of a therapeutically effective amount of konjac or glucomannan as defined above. Further the invention is directed to a lipase inhibitor and glucomannan or konjac as defined above for simultaneous, separate or sequential use for the treatment and prevention of obesity.
FIG. 1 displays test emulsions of konjac after centrifugation at 3100 g for t=1 min (a) and t=300 min (b), respectively. After a centrifugation time of t=300 min, only for emulsions containing konjac in concentrations higher than 1.5% (w/w) a weak emulsification stabilization is observed.
FIG. 2 shows test emulsions of konjac after centrifugation at 3100 g for t=1 min (a) and t=300 min (b), respectively. The emulsions contained 1.0% (w/w) konjac at different pH values. After a centrifugation time of t=300 min minor emulsion stabilization was observed at pH 6 and 7, respectively. For all other emulsions extensive coalescence was observed.
FIG. 3: The free oil reducing effect of different types of glucomannan in % relative to controls (data as means ±SE).
In accordance with this invention the administration of glucomannan in conjunction with lipase inhibitors for combating obesity reduces the gastro-intestinal side effects produced by the lipase inhibitor such as oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence in humans.
In accordance with an embodiment of this invention, pharmaceutical compositions are provided which contain the lipase inhibitors, preferably orlistat, and glucomannan. These compositions may contain pharmaceutically acceptable excipients. In accordance with one embodiment, the pharmaceutical composition contains from about 0.1% by weight to about 10% by weight, based upon the weight of the composition, of the lipase inhibitor and from about 10% by weight to about 75% by weight, based upon the weight of the composition, of glucomannan and from about 0.1% to 90% by weight, based upon the weight of the composition of one or more pharmaceutically acceptable excipients. Generally it is preferred that the composition of this invention be formulated in a unit oral dosage form.
In accordance with another embodiment of this invention there is provided a method for combating obesity in human patients by administering to said human patients the lipase inhibitor, preferably orlistat, in an effective amount to treat said obesity, in conjunction with glucomannan. In accordance with a preferred embodiment both the glucomannan and lipase inhibitor can be orally administered in conventional oral dosage forms such as through the compositions of this invention. In accordance with this invention, the glucomannan and lipase inhibitor can be administered simultaneously, separately or sequentially for carrying out the method of this invention. Generally, it is preferred, when separately administered, the two components i.e. the lipase inhibitor and the glucomannan be administered within two hours of each other. In accordance with this invention the glucomannan which is administered in conjunction with lipase inhibitor is administered in an amount of about 0.5 g to 10 g per day after administration of lipase inhibitor. In accordance with this invention the lipase inhibitor is generally administered from 2 to preferably 3 times per day.
In accordance with this invention any effective amount of lipase inhibitors for combating obesity can be administered to human patients. The use of these lipase inhibitors and their dosages are well known for combating obesity. By combating obesity, it is meant that the composition of this invention can be utilized either for prevention and/or treatment of obesity. In addition the compositions of this invention can contain any effective amount of the lipase inhibitor needed for administration to combat obesity.
Where the glucomannan is to be separately or simultaneously administered, in accordance with another embodiment of this invention, kits can be provided containing the lipase inhibitor, preferably orlistat as one component, and the glucomannan as the second component. Preferably, each of the components contains the glucomannan and lipase inhibitor, such as orlistat, in the compositions in oral unit dosage forms. The first or lipase inhibitor component of the kit can contain from 1 to 100 oral dosage units of the lipase inhibitor, such as orlistat, and the second or glucomannan component contains from about 1 to 100 oral dosage units of glucomannan. Lipase inhibitor is present in each oral unit dosage form in an amount of from 5 to 120 mg and the glucomannan is provided in a separate oral unit dosage form which constitutes the second component. In accordance with a preferred embodiment of this invention, the glucomannan can be provided in the separate oral unit dosage form in an amount of from about 0.5 g to about 10 g. Generally it is preferred that the orilstat be administered in an amount of from 16 mg to 720 mg in each unit oral dosage form contained within the first component of the kit.
In accordance with this invention, it has been found that glucomannan can be administered such as glucomannan itself or in the form of konjac, e.g. konjac flour, in any amount sufficient to reduce the gastro-intestinal adverse events (GI-AE) commonly observed after administration of a lipase inhibitor such as orlistat or artificial fat substitutes. Therefore the method of this invention involves the use of glucomannan in an amount sufficient to reduce the gastro-intestinal adverse effects observed after administration of a lipase inhibitor. These effects include oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence in humans.
Konjac (Amorphophallus konjac) is a plant, the tuber of which is the source of a well-known foodstuff in China and Japan, namely konjac flour. This flour comprises a highly viscous sol of glucomannan and soluble starches when reconstituted in water. The principal soluble constituent is glucomannan (formula II), a polysaccharide comprised of D-glucose and D-mannose, which is useful as an ingredient in various foodstuffs, as well as in industrial applications such as films, oil drilling fluids and paints.
Accordingly, the present invention refers to a composition comprising a lipase inhibitor and glucomannan. Unless otherwise indicated the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein.
The term "lipase inhibitor" refers to compounds which are capable of inhibiting the action of lipases, for example gastric and pancreatic lipases. For example, orlistat and lipstatin as described in U.S. Patent No. 4,598,089 are potent inhibitors of lipases. Lipstatin is a natural product of microbial origin, and orlistat is the result of a hydrogenation of lipstatin. Other lipase inhibitors include a class of compound commonly referred to as panclicins. Panclicins are analogues of orlistat (Mutoh et al, J. Antibiot., 47(12):1369-1375 (1994)). The term "lipase inhibitor" refers also to polymer bound lipase inhibitors for example described in International Patent Application WO 99/34786 (Geltex Pharmaceuticals Inc.). These polymers are characterized in that they have been substituted with one or more groups that inhibit lipases. The term "lipase inhibitor" also comprises pharmaceutically acceptable salts of these compounds. The term "lipase inhibitor" also refers to 2-oxy-4H-3,1-benzoxazin-4-ones which have been described in International Patent Application WO 00/40569 (Alizyme Therapeutics Ltd.), e.g. 2-decyloxy-6-methyl-4H-3,1-benzoxazin-4-one, 6-methyl-2-tetradecyloxy-4H-3,1-benzoxazin-4-one, and 2-hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one and other oxetanones described for example in International Patent Applications WO 01/32616, WO 01/32669 and WO 01/32670. Most preferably, the term "lipase inhibitor" refers to orlistat.
Orlistat is a known compound useful for the control or prevention of obesity and hyperlipidemia. See, U.S. Pat. No. 4,598,089, issued Jul. 1, 1986, which also discloses processes for making orlistat and U.S. Pat. No.6,004,996, which discloses appropriate pharmaceutical compositions. Further suitable pharmaceutical compositions are described for example in International Patent Applications WO 00/09122 and WO 00/09123. Additional processes for the preparation of orlistat are disclosed in European Patent Applications Publication Nos. 185,359, 189,577, 443,449, and 524,495.
Orlistat is preferably orally administered from 60 to 720 mg per day in divided doses two to three times per day. Preferred is wherein from 180 to 360 mg, most preferably 360 mg per day of a lipase inhibitor is administered to a human subject, preferably in divided doses two or, particularly, three times per day. The subject is preferably an obese or overweight human, i.e. a human with a body mass index of 25 or greater. Generally, it is preferred that the lipase inhibitor be administered within about one or two hours of ingestion of a meal containing fat.
Orlistat can be administered to humans in conventional oral compositions, such as tablets, coated tablets, hard and soft gelatin capsules, emulsions or suspensions. Examples of carriers which can be used for tablets, coated tablets, dragées and hard gelatin capsules are lactose, other sugars and sugar alcohols like sorbitol, mannitol, maltodextrin, or other fillers; surfactants like sodium lauryl sulfate, Brij 96, or Tween 80; disintegrants like sodium starch glycolate, maize starch or derivatives thereof; polymers like povidone and crospovidone; talc; stearic acid or its salts and the like. Suitable carriers for soft gelatin capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. Moreover, the pharmaceutical preparations can contain preserving agents, solubilizers, stabilizing agents, wetting agents, emulsifying agents, sweetening agents, coloring agents, flavoring agents, salts for varying the osmotic pressure, buffers, coating agents and antioxidants. They can also contain still other therapeutically valuable substances. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods known in the pharmaceutical art. Preferably, orlistat is administered according to the formulation shown in the Examples and in U.S. Pat. No. 6,004,996, respectively.
The term "konjac flour" refers to a hydrocolloidal polysaccharide obtained from the tubers of species of Amorphophallus konjac. The perennial tuber is unique to Asia and especially cultivated in Japan. Konjac flour is a high molecular weight, nonionic glucomannan consisting primarily of mannose and glucose molecules combined in a mole ratio of 1.6:1.0. It is a slightly branched polysaccharide connected by beta 1-4 linkages and has an average molecular weight ranging from 200,000 to 2,000,000 daltons. Acetyl groups along the glucomannan backbone contribute to its solubility and are located, on average, at every 9 to 19 sugar unit. Refined konjac flour is easily soluble in cold water and forms a highly viscous solution with a pH between 4.0 and 7.0. Addition of a mild alkaline solution results in the formation of a heat-stable gel that resists melting, even under extended heating conditions. The purification process for konjac flour is carried out in large-scale extraction plants. The konjac tubers are first pulverized, and then the collected glucomannan particles are polished in order to dislodge and extract noxious materials adhering to them. This process yields a refined konjac flour with high degree of purity that improves product solubility, stability and overall functionality. The particles are tasteless, odorless and white in color.
Konjac flour and glucomannan (PROPOL®, RHEOLEX®) are commercially available products (Kyoei Konnyaku, Inc., Behr, Wunderlich & Co., Provisco, FMC Biopolymers, Naturland, SiberHegner and Co. Ltd.). The preparation and use have been described e.g. in U.S. Pat. Nos. 3,767,424,3,973,007,4,588,589, 5,486,364, 5,486,364, 5,733,593, 5,536,521, 6,126,906, etc.
The term "pharmaceutically acceptable" as used herein means that the corresponding compounds are acceptable from a toxicity viewpoint.
In more detail, the present invention relates to a pharmaceutical composition comprising a lipase inhibitor and glucomannan. Optionally this composition may contain one or more pharmaceutically acceptable excipients. The glucomannan may be provided in form of konjac. Preferably, the konjac contains at least 80% by weight glucomannan, more preferably at least 90% by weight glucomannan. The glucomannan or konjac may be provided in form of konjac powder, e.g. konjac flour. Preferably the lipase inhibitor is orlistat. These 80% by weight are based on the total weight of the composition.
Pharmaceutical compositions incorporating both a compound of a lipase inhibitor and glucomannan are important embodiments of the present invention. Such pharmaceutical compositions comprise a therapeutically effective amount of each of the compounds for the given purpose. Each dosage unit can obtain the daily doses of both compounds or may contain a fraction of the daily dose, such as one-third of the doses. Alternatively, each dosage unit may contain the entire dose of one of the compounds, and a fraction of the dose of the other compound. In such case the patient would daily take one of the combination dosage units, and one or more units containing only the other compound.
In a preferred embodiment of the present invention the composition comprises a) 0.1 to 20% (w/w) lipase inhibitor, b) 10 to 75% (w/w) glucomannan such as konjac, and c) 0.1 to 90% (w/w) of one or more pharmaceutically acceptable excipients. More preferably, a composition may comprise a) 0.1 to 10% (w/w) lipase inhibitor, b) 20 to 75% (w/w) glucomannan and c) 0.1 to 90% (w/w) of one or more pharmaceutically acceptable excipients. Preferably, the amount of one or more pharmaceutically acceptable excipients is from about 5 to 50% (w/w), more preferably 5 to 20%. In more detail, the composition may contain a) from about 5 to about 1000 mg lipase inhibitor, e.g. orlistat, in an amount of e.g. from about 10 to about 500 mg lipase inhibitor, preferably from about 20 to about 100 mg lipase inhibitor, e.g. from about 10 to about 360 mg orlistat, more preferably from about 30 to about 120 mg orlistat, more preferably from about 40 to about 80 mg orlistat and b) from about 0.5 to about 10 g glucomannan, preferably from about 0.5 to about 8 g glucomannan, and more preferably from about 0.5 to about 6 g glucomannan. The weight percent is based upon the total weight of the composition
The pharmaceutically acceptable excipients may be selected from the group consisting of fillers, surfactants, disintegrants, binders, lubricants, flowability enhancers, sweeteners, and colorants, e.g. a composition may comprise of a) about 5 to about 1000 mg lipase inhibitor; b) about 0.5 to about 10 g glucomannan; and optionally pharmaceutically acceptable excipients selected from the group of about 0.1 to about 10 g fillers, about 0.05 to about 5.0 g surfactants, about 0.05 to about 2.0 g disintegrants, about 0.02 to about 5.0 g binder, about 0.001 to about 1.0 g lubricants, about 0.1 to about 5.0 g flowability enhancers, about 0.01 to about 4.0 g sweeteners, and about 0.001 to about 0.5 g colorants.
The pharmaceutically acceptable excipients may be selected from the group consisting of fillers, e.g. sugars and/or sugar alcohols, e.g. lactose, sorbitol, mannitol, maltodextrin, etc.; surfactants, e.g. sodium lauryl sulfate, TPGS, Brij 96 or Tween 80; disintegrants, e.g. sodium starch glycolate, maize starch or derivatives thereof; binder, e.g. povidone, crosspovidone, polyvinylalcohols, hydroxypropylmethylcellulose; lubricants, e.g. stearic acid or its salts; flowability enhancers, e.g. silicium dioxide; sweeteners, e.g. aspartame; and/or colorants, e.g. β-carotene.
In a preferred embodiment of the present invention the composition comprises a) about 0.1 to about 20% (w/w) lipase inhibitor; b) 10 to about 75% (w/w) glucomannan such as konjac; and optionally pharmaceutically acceptable excipients selected from the group of about 0.1 to about 20% (w/w) fillers, about 0.1 to about 10% (w/w) surfactants, about 0.1 to about 10% (w/w) disintegrants, about 0.1 to about 10% (w/w) binder, about 0.1 to about 10% (w/w) lubricants, about 0.1 to about 10% (w/w) flowability enhancers, about 0.1 to about 10% (w/w) sweeteners, and about 0.1 to about 5% (w/w) colorants.
In more detail, the composition may contain a) from about 5 to about 1000 mg lipase inhibitor, e.g. orlistat, in an amount of e.g. from about 10 to about 500 mg lipase inhibitor, preferably from about 20 to about 100 mg lipase inhibitor, e.g. from about 10 to about 360 mg orlistat, more preferably from about 30 to about 120 mg orlistat, more preferably from about 40 to about 80 mg orlistat and b) from about 0.5 to about 10 g glucomannan, preferably from about 0.5 to about 8 g glucomannan, and more preferably from about 0.5 to about 6 g glucomannan.
Oral dosage forms are the preferred compositions for use in the present invention and these are the known pharmaceutical forms for such administration, for example tablets, capsules, bars, sachets, granules, syrups and aqueous or oily suspensions. The pharmaceutically acceptable excipients (diluents and carriers) are known in the pharmacist's art. Tablets may be formed from a mixture of the active compounds with fillers, for example calcium phosphate; disintegrating agents, for example maize starch, lubricating agents, for example magnesium stearate; binders, for example microcrystalline cellulose or polyvinylpyrrolidone and other optional ingredients known in the art to permit tabletting the mixture by known methods. Similarly, capsules, for example hard or soft gelatin capsules, containing the active compound with or without added excipients, may be prepared by known methods. The contents of the capsule may be formulated using known methods so as to give sustained release of the active compound. For example, the tablets and capsules may conveniently each contain the amounts of lipase inhibitor and glucomannan as described above.
Other dosage forms for oral administration include, for example, aqueous suspensions containing the active compounds in an aqueous medium in the presence of a non-toxic suspending agent such as sodium carboxymethylcellulose, and oily suspensions containing the active compounds in a suitable vegetable oil, for example arachis oil, olive oil or myritol 318. The active compounds may be formulated into granules with or without additional excipients. The granules may be ingested directly by the patient or they may be added to a suitable liquid carrier (e.g. water) before ingestion. The granules may contain disintegrants, e.g. an effervescent pair formed from an acid and a carbonate or bicarbonate salt to facilitate dispersion in the liquid medium.
In the compositions of the present invention the active compounds may, if desired, be associated with other compatible pharmacologically active ingredients. Optionally vitamin supplements may be administered with the compounds in accordance with the present invention. Both compounds, the lipase inhibitor and glucomannan, may be administered simultaneously, separately or sequentially (e.g. orlistat as described above and glucomannan in the evening). Preferably, the compounds or compositions are administered during a meal or 1-2 hours before or after a meal. The amount of glucomannan to be administered will depend on a number of factors including the age of the patient, the severity of the condition and the past medical history of the patient and lies within the discretion of the administering physician.
The invention will be better understood by reference to the following examples which illustrate but do not limit the invention described herein.
EXAMPLES Example 1 In Vitro Studies
Surprisingly, it has now been observed that glucomannan is active in reducing gastro-intestinal adverse events (GI-AE) commonly observed after administration of a lipase inhibitor such as orlistat.
The interaction of konjac (source of glucomannan) with oil and water was examined by an absorption test. Samples of the compound were brought into contact with either soya oil or simulated intestinal fluid (SIF, phosphate buffer without pancreatin) and incubated for 24 h at 37° C. Remaining liquid was separated from the solid material by means of centrifugation (3×5 min at 3100 g). Whereas in SIF significant swelling of the polymer was observed, no swelling occurred in soya oil. The SIF and soya oil absorption capacity of konjac was calculated to 4.8 g/g and 0.5 g/g, respectively. The low amount of oil binding demonstrates its poor lipophilicity.
The coalescence behavior of emulsions stabilized with konjac was probed using a centrifugal method. With this in vitro method, both concentration and pH-depended emulsion stabilities were examined. The results of these stability studies are listed in Tables 1 and 2. The use of konjac in less than 0.5% (w/w) revealed very unstable emulsions resulting in rapid oil/water phase separation (Table 1). Even at konjac concentrations of 1.0% (w/w), emulsions remained rather unstable and clear phase separation was obtained after 10 min centrifugation. Only emulsions containing more than 1.0% (w/w) konjac exhibited after centrifugation times of up to t=300 min medium stability with the emulsion partly broken (FIG. 1).
Stability of konjac test emulsions at various concentrations c and centrifugation times t.
Emulsion Stability Konjac t/min
c (% w/w) 1 10 40 70 100 130 160 220 300
0.01 l* l l l l l l l l 0.1 l l l l l l l l l 0.5 l l l l l l l l l 1.0 m m l l l l l l l 1.5 h m m m m m m m m 2.0 h m m m m m m m m
*l = low stability: oil and water form two distinct clearly separated phases;
m = medium stability: emulsion partly broken;
h = high stability: no indications of coalescence, optically non-transparent, stable emulsion
FIG. 1 displays test emulsions of konjac after centrifugation at 3100 g for t=1 min (a) and t=300 min (b), respectively. After centrifugation times of t=300 min, only for emulsions containing konjac in concentrations higher than 1.5% (w/w) a weak emulsification stabilization is observed.
In order to investigate emulsion stability at different pH values, test emulsions with a constant konjac concentration of c=1.0% (w/w) covering a pH range of 4 to 9 were prepared (Table 2). At both extreme pH values of 4 and 9 very poor emulsification of the test emulsions was observed, resulting in instantaneous layering of the oil phase. Whereas at pH=8 short centrifugation times of less than 30 min also led to complete emulsion breaking, emulsions at pH=5 revealed slightly higher stability. Here, coalescence occurred at centrifugation times higher than 60 min. The pH optimum in terms of emulsion stability was observed at slightly acidic to neutral pH values (pH 6-7).
Stability of konjac test emulsions at various pH values and centrifugation times t.
pH 1 30 60 120 300 4 l* l l l l 5 m m m l l 6 m m m m m 7 m m m m m 8 m l l l l 9 l l l l l
FIG. 2 shows test emulsions of konjac after centrifugation at 3100 g for t=1 n (a) and t=300 min (b), respectively. The emulsions contained 1.0% (w/w) konjac at different pH values. After centrifugation for t=300 min minor emulsions stabilization was observed at pH 6 and 7, respectively. For all other emulsions extensive coalescence was observed.
Solutions of konjac with concentrations of 0.01%, 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% (w/w) in a simulated intestinal fluid (SIF) without pancreatin according to USP XXII, p. 1789 (pH=7.5, potassium dihydrogenphosphate buffer) were prepared. To 18 g of such a solution 2 g of soya oil (FLUKA, 85471) was added yielding a final oil concentration with respect to the aqueous phase of 10% w/w. Soya oil was not purified and used as received. Emulsions were then prepared using a Miccra homogenization apparatus at 28.000 rpm (level E) and a homogenization time of 1 min. As a reference, mixtures of soya oil and phosphate buffer were used without addition of surfactant. Dying of the emulsion with nile red and subsequent analysis under an optical microscope revealed that the emulsions were of the oil-in-water type. Median droplet size analysis immediately after preparation using a Galai CIS-1 apparatus yielded values of typically 20-30 μm. Glass capillaries of height ca. 95 mm and a diameter of ca. 1.7 mm (glass thickness ca. 0.8 mm) were filled up to ca. 6.5 cm with the pre-prepared emulsions by means of a syringe and centrifuged at a maximum speed of 5000 rpm (Eppendorf, Centrifuge 5403, Rotor No 16A4-44) which corresponds to a centrifugal force of 3100 g (bottom of glass capillary). In order to record the demulsification process, the centrifugation process was interrupted at defined time intervals (t=1, 10, 40, 70, 100, 130, 160, 220, 300 min) and the capillaries placed on an optical scanner operating in transmission mode (Bio-Rad GS-700 Imaging Densitometer). The distance between the capillaries was kept constant by means of a house-made sample holder. All measurements were conducted at room temperature.
Example 2 In Vivo Studies I
To test substances that will ameliorate the oil-related side effects associated with orlistat treatment, an acute human model was developed. Healthy volunteers received orlistat alone or in combination with the test substance during 3 consecutive meals (3-meal test). The modified orlistat formulations used in these 3-meal tests induce 70-80% fat excretion. A questionnaire was given to the volunteers to record side effects. The most severe oil related side effect is oily spotting (uncontrolled loss of oil). This side effect is difficult to quantify accurately in an acute model, however, in some volunteers a spontaneous separation of fat from formed stool was observed. This amount of fat, called free oil (mainly containing triglycerides) was isolated and weighted.
The amount of free oil was used as a surrogate marker for the oily spotting as this is considered necessary for the appearance of oily spotting.
Two clinical studies have been conducted to investigate the gastro-intestinal adverse event modifying effects of numerous substances. It appears that volunteers show an individual sensitivity to the orlistat-related gastro-intestinal side effects. Therefore, each volunteer was used as his own control (treatment with orlistat alone). Volunteers showing a weak sensitivity to orlistat related side effects were excluded from the test evaluation. For a given volunteer a substance is considered as positive when the free oil quantity is reduced by at least 50% compared to the control value (orlistat alone).
Glucomannan was tested as konjac powder. The konjac powder is obtained from the root of a tree (Amorphophallus konjac) and this the natural source of glucomannan. This substance was tested in the acute side effect model at the dosage of 4 g/meal. Among the 5 tested volunteers 4 had a decrease by at least 50% of the free oil generated without glucomannan (see table 3). Volunteers treated with glucomannan/orlistat had no fat excretion decrease (compared to volunteers treated with orlistat alone, data not shown) suggesting no interaction of glucomannan with orlistat. No major AEs associated with the glucomannan treatment has been reported.
Konjac (Glucomannan) results
Free oil production Glucomannan (g/week)
(Konjac; 4 g/meal) orlistat orlistat + Konjac
Test 1 11 8 9 0 Test 2 39 16 17 8 40 6
Positive/total (50% < control) 4/5
Example 3 In Vivo Studies II
The results from the in vitro experiments were further supported by studies carried out with an in vivo mouse model. The experiment is based on the observation that mice under a high fat diet with orlistat or other lipase inhibitor treatment distribute the excreted free oil over their furs while grooming. Several types and formulations of glucomannan were examined for their ability to reduce or eliminate the production of free oil. The results obtained are shown in FIG. 3.
Example 4 Orlistat Pharmaceutical Compositions
Quantity Ingredient mg/Capsule
orlistat 120.00 microcrystalline cellulose (AVICEL PH-101) 93.60 sodium starch glycolate (PRIMOJEL) 7.20 sodium lauryl sulfate 7.20 polyvinylpyrrolidone (Povidone K-30) 12.00 talc 0.24 Total 240.24 mg
1. Blend orlistat, microcrystalline cellulose, and sodium starch glycolate in a suitable mixer.
2. Granulate with a solution of polyvinylpyrrolidone and sodium lauryl sulfate in purified water.
3. Pass the granulation through an extruder and pass the extrudate through a spheronizer to form pellets.
4. Dry the pellets at 30° C.
5. Add talc and mix.
6. Fill into hard gelatin capsules.
orlistat 60 microcrystalline cellulose 46.8 sodium starch glycolate 3.6 sodium lauryl sulfate 3.6 polyvinylpyrrolidone 6.0 talc 0.12 Total 120.12 mg
2. Granulate with solution of polyvinylpyrrolidone and sodium lauryl sulfate in purified water.
Ingredient Quantity mg/Capsule
orlistat 60 120 lactose 40 80 microcrystalline cellulose 60 120 sodium lauryl sulfate 5.7 11.4 sodium starch glycolate 20 40 polyvinylpyrrolidone 10 20 talc 0.2 0.4 Total 195.9 mg 391.8 mg
1. Blend orlistat, lactose, microcrystalline cellulose and sodium starch glycolate in a suitable mixer.
Example 5 Glucomannan Pharmaceutical Compositions
Quantity g/Chewable Ingredient tablet
glucomannan 1.5 g sorbitol 1.1 g lactose anhydrous 0.376 g talc 0.16 g sodium stearyl fumarate 0.064 g Total 3.2 g
1. Blend glucomannan, sorbitol and lactose in a suitable mixer.
2. Pass the powder mixture through a sieve.
3. Add talc and sodium stearyl fumarate and mix.
4. Directly compress the powder mixture to a chewable tablet.
Ingredient Quantity g/Sachet
glucomannan 4 g aspartame 0.5 g beta-carotene 0.001 g Total 4.501 g
1. Fill glucomannan in a suitable high shear mixer.
2. Granulate with a solution/colloidal suspension of Aspartame and beta-carotene in purified water.
3. Dry the granules at 60° C.
4. Pass the dry granulation through a sieve.
5. Fill into sachets.
glucomannan 0.5 g lactose 0.5 g microcrystalline cellulose 1.31 g sodium lauryl sulfate 0.09 g sodium starch glycolate 0.3 g polivinylpyrrolidone 0.15 g talc 0.15 g Total 3.0 g
1. Blend glucomannan, lactose, microcrystalline cellulose, sodium starch glycolate in a suitable mixer.
2. Dissolve sodium lauryl sulfate and polivinyl pyrrolidone in purified water.
3. Granulate with the liquid.
4. Pass the granulation through an extruder and pass the extrudate through a spheronizer to form round pellets.
6. Add talc and mix
7. Compress the pellets to a chewable tablet.
Example 8 Orlistat/Glucomannan Pharmaceutical Compositions
orlistat 0.06 g glucomannan 0.75 g lactose 0.5 g microcrystalline cellulose 1.31 g sodium lauryl sulfate 0.09 g sodium starch glycolate 0.3 g polivinylpyrrolidone 0.15 g talc 0.15 g Total 3.31 g
1. Blend orlistat, glucomannan, lactose, microcrystalline cellulose, sodium starch glycolate in a suitable mixer.
5. Dry the pellets at maximum 35° C.
orlistat 0.12 g glucomannan 4 g saccharose 2.8 g beta-carotene 0.001 g silicium dioxide 0.5 g Total 7.421 g
1. Blend orlistat, glucomannan, sachharose in a suitable mixer.
2. Mix in several portion with the mixture of beta-carotene and silicium dioxide.
Example 10 Orlistat/Glucomannan Pharmaceutical Compositions
orlistat 0.12 g glucomannan 2.0 g sodium starch glycolate 0.1 g microcrystalline cellulose 0.2 g sodium lauryl sulfate 0.03 g crospovidone 0.1 g aspartame 0.15 g talc 0.15 g magnesium stearate 0.03 g Total 2.85 g
1. Blend orlistat, glucomannan, microcrystalline cellulose, sodium starch glycolate and crospovidone in a suitable mixer.
2. Granulate with a solution/colloidal suspension of sodium lauryl sulfate and aspartame in purified water.
3. Pass the granulate through a sieve.
5. Pass the dry granules through a sieve.
6. Mix with talc and magnesium stearate.
7. Compress to chewable tablet.
1. A pharmaceutical composition comprising from about 0.1% by weight to about 20% by weight, based upon the weight of the composition, of a lipase inhibitor and from about 10% by weight to about 75% by weight, based upon the weight of the composition, of glucomannan and from about 0.1% to about 90% by weight, based upon the weight of the composition, of one or more pharmaceutically acceptable excipients.
2. The composition of claim 1 wherein the glucomannan is present as konjac.
3. The composition of claim 2 wherein the konjac is present as konjac flour.
4. The composition of claim 2 where in the konjac contains at least 80% by weight of glucomannan.
5. The pharmaceutical composition of claim 4 wherein the konjac contains at least 90% by weight glucomannan.
6. The composition of claim 1 wherein the lipase inhibitor is present in an amount of from about 0.1% by weight to about 10%, based upon the weight of said composition, and glucomannan is present in an amount of from 20% to 75% by weight, based upon the weight of the composition.
7. The composition of claim 1, wherein the pharmaceutically acceptable excipient is selected from the group consisting of fillers, surfactants, disintegrants, binders, lubricants, flowability enhancers, sweeteners, and colorants.
8. The composition of claim 7 wherein the composition comprises
a) from about 0.1% to about 20% (w/w) lipase inhibitor;
b) from about 10 to about 75% (w/w) glucomannan; and
pharmaceutically acceptable excipients selected from the group consisting of, from about 0.1 to about 20% (w/w) fillers, from about 0.1 to about 10% (w/w) surfactants, about 0.1 to about 10% (w/w) disintegrants, from about 0.1 to about 10% (w/w) binder, about 0.1 to about 10% (w/w) lubricants, from about 0.1 to about 10% (w/w) flowability enhancers, about 0.1 to about 10% (w/w) sweeteners, from about 0.1 to about 5% (w/w) colorants and mixtures thereof, with all said weight percents being based upon the weight of the composition.
9. The composition of claim 1 wherein the composition contains from about 5 mg to about 1,000 mg of said lipase inhibitor and from about 0.5 g to about 10 g of glucomannan.
10. The composition of claim 9 wherein said composition is in unit oral dosage form.
11. The composition of claim 10 wherein the composition contains from about 0.5 to 6 grams of glucomannan.
12. The composition of claim 11 wherein said composition contains from about 10 mg to 500 mg of the lipase inhibitor.
13. The composition of claim 12 wherein said composition contains from about 10 mg to about 360 mg of the lipase inhibitor.
14. The composition of claim 9, wherein the pharmaceutically acceptable excipient is selected from the group consisting of fillers, surfactants, disintegrants, binders, lubricants, flowability enhancers, sweeteners, and colorants.
15. The composition of claim 14, comprising
a) from about 5 to about 1000 mg of said lipase inhibitor;
b) from about 0.5 to about 10 g glucomannan; and
pharmaceutically acceptable excipients selected from the group consisting of from about 0.1 to about 10 g fillers, from about 0.05 to about 5.0 g surfactants, from about 0.05 to about 2.0 g disintegrants, from about 0.02 to about 5.0 g binder, from about 0.001 to about 1.0 g lubricants, from about 0.1 to about 5.0 g flowability enhancers, from about 0.01 to about 4.0 g sweeteners, from about 0.001 to about 0.5 g colorants and mixtures thereof.
16. The composition of claim 1 wherein said lipase inhibitor is orlistat.
17. The composition of claim 16 wherein the glucomannan present as konjac.
18. The composition of claim 17 wherein the konjac is present as konjac flour.
19. The composition of claim 18 where in the konjac contains at least 80% by weight of glucomannan.
20. The pharmaceutical composition of claim 19 wherein the konjac contains at least 90% by weight glucomannan.
21. The composition of claim 16 wherein the glucomannan is present in said composition in an amount of from about 20% to 75% by weight, based upon the weight of the composition and the orlistat is present in an amount of from 1% to about 10% based upon the weight of the composition.
22. The composition of claim 16, wherein the pharmaceutically acceptable excipient is selected from the group consisting of fillers, surfactants, disintegrants, binders, lubricants, flowability enhancers, sweeteners, and colorants.
23. The composition of claim 22 wherein the composition comprising from
a) about 0.1% to about 20% (w/w) of orlistat;
b) about 10 to about 75% (w/w) glucomannan; and
pharmaceutically acceptable excipients selected from the group consisting of from about 0.1 to about 20% (w/w) fillers, from about 0.1 to about 10% (w/w) surfactants, from about 0.1 to about 10% (w/w) disintegrants, from about 0.1 to about 10% (w/w) binder, from about 0.1 to about 10% (w/w) lubricants, from about 0.1 to about 10% (w/w) flowability enhancers, from about 0.1 to about 10% (w/w) sweeteners, from about 0.1 to about 5% (w/w) colorants and mixtures thereof wherein the percents are based upon the weight of the composition.
24. The composition of claim 16 wherein the composition contains from about 5 mg to about 1,000 mg of said lipase inhibitor and from about 0.5 g to about 10 g of glucomannan.
25. The composition of claim 16 wherein said composition contains from about 10 mg to 500 mg of orlistat.
26. The composition of claim 24 wherein said composition contains from about 10 mg to about 360 mg of orlistat.
27. The composition of claim 16, comprising from:
a) about 5 to about 1000 mg orlistat;
b) about 0.5 to about 10 g glucomannan; and
28. A method of combating obesity in human patients comprising administering to said human patients a lipase inhibitor in an amount effective to combat said obesity, said lipase inhibitor being administered in conjunction with glucomannan, said glucomannan being administered in an amount sufficient to reduce the gastro-intestinal adverse events caused after administration of a lipase inhibitor.
29. The method of claim 28 wherein the lipase inhibitor is administered for treatment or prevention of obesity.
30. The method of claim 29 wherein said lipase inhibitor and glucomannan are administered simultaneously or sequentially or separately.
31. The method of claim 30 wherein said lipase inhibitor is administered in an amount of from about 5 mg to 1000 mg per day and the glucomannan is administered in an amount of from 0.5 to 10 g per day.
32. The method of claim 31 wherein said lipase inhibitor is administered in an amount of from about 60 mg to 720 mg per day.
33. The method of claim 31 wherein said administration is oral.
34. The method of claim 33 wherein the glucomannan and the lipase inhibitor are administered within two hours of each other.
35. The method of claim 31 wherein the glucomannan is administered for combating gastro-intestinal side effects caused by the lipase inhibitor, which side effects are selected from the group consisting of oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence.
36. The method of claim 33 wherein the combination of lipase inhibitor and the glucomannan are administered from two to three times per day.
37. The method of claim 35 wherein the combination is orally administered.
38. The method of claim 31 wherein said lipase inhibitor is orlistat.
39. The method of claim 38 wherein orlistat is orally administered in an amount of from about 10 mg to about 500 mg per day.
40. The method of claim 39 wherein the orlistat is administered in an amount from about 10 mg to 360 mg per day.
42. The method of claim 41 wherein the orlistat is administered in an amount from about 40 mg to 80 mg per day.
43. The kit for the treatment of obesity containing as a first component a lipase inhibitor and as a second component glucomannan.
44. The kit of claim 43 wherein both of the components within the kit contain unit oral dosage forms to be administered to a human patient.
45. The kit of claim 44 wherein said lipase inhibitor is orlistat.
46. The kit of claim 45 wherein the oral unit dosage forms which comprise the first component orlistat each contain from about 5 to about 120 mg of the orlistat and the unit oral dosage forms which comprise the second component glucomannan each contain from about 0.5 to about 10 g of glucomannan.
47. The kit of claim 45 wherein the oral unit dosage forms which comprise the first component orlistat each contain from about 16 mg to about 720 mg of orlistat and the unit oral dosage forms which comprise the second component glucomannan each contain from about 0.5 to about 10 g of glucomannan.
48. The kit of claim 46 wherein each component contains from 1 to 100 oral unit dosage forms of glucomannan and from 1 to 100 oral unit dosage forms of orlistat.
Filed: Feb 7, 2006
Patent Grant number: 7816342
Inventors: Jacques Bailly (Rixheim), Rainer Martin (Grenzach-Wyhlen), Susanne Raab (Leinfelden-Echterdingen)
Current U.S. Class: 514/54.000; 514/449.000
International Classification: A61K 31/716 (20060101); A61K 31/365 (20060101);


text:
Jonathan Robson hasn't been seen since Saturday morning - and police are 'really concerned'
Police believe he may have used public transport to travel from Middlesbrough to Hartlepool
Samuel Jones
Officers are really concerned for the welfare of missing Jonathan Robson, 30 (Image: Cleveland Police)
Police are "really concerned" for the welfare of a man missing since the early hours of Saturday morning.
Jonathan Robson, 30, is believed to have been last seen in Middlesbrough town centre.
Mr Robson has links to Hartlepool and is described as a white male, of slim build, 6 ft 1" tall with brown hair.
It is unknown what he was last seen wearing but police believe he may have used public transport to travel to Hartlepool.
A Cleveland Police spokesperson said: "Anyone who may have seen him, or anyone who may have information regarding his whereabouts, is asked to contact Cleveland Police on 101, quoting event number 208225."
Several police units swoop on Stockton street - with 'arrests made'
Like the Teesside Live Facebook page to get the latest news in your feed and join our group dedicated to court and crime coverage. You can also follow us on Twitter and Instagram.
To receive alerts on the latest breaking news, download our free app for Apple or Android here . Have a story? Contact us on social media or email news@gazettemedia.co.uk .
Central Middlesbrough


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AcaDemon»
The Cuban Adjustment Act
The Cuban Adjustment Act Analytical Essay by Lucia
Looks at the Cuban Adjustment Act (CAA) and its 1995 revision known as the wet-foot dry-foot policy from a social work perspective.
# 150530 | 1,780 words | 18 sources | APA | 2011 |
Published on Mar 02, 2012 in Sociology (Social Work) , History (U.S. Post-Modern 1965-Present) , Latin-American Studies (Immigration/Emigration issues)
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This paper explains that the 1966 Cuban Adjustment Act (CAA) grants Cuban asylum seekers permanent residency after one year of living in the United States; however, the 1995 revision, known as the wet-foot dry-foot policy, restricts this policy only to those who actually reach the US shore thereby returning those intercepted at sea. Next, the author reviews the history of Cuban-United States relations and identifies the various waves of Cuban immigrants starting in the early 1960s and continuing to the 1994 wave known as the Balsero Crisis. The paper points out several social welfare problems presented in the CAA and wet-foot dry-foot policy and underscores, from a social work perspective, the social injustice of this act thus discovering that its agenda is not humanitarian but rather anti-communism.
History of Cuban-United States Relations and Cuban Immigration
Social Welfare Problem
Benefits, Limitations, and Unintended Consequences of the CAA
A Social Work Perspective
"The dismal economic situation in Cuba led to another immigrant wave in the summer of 1994. This wave is also known as the Balsero Crisis, in which 30,000 Cubans came to the United States on boats. Such a large influx triggered the United States government to once and for all restrict Cuban migration to the States. A modification of the CAA was enacted in May 2, 1995 by the Clinton Administration that granted legal entry in the United States only to the refugees who reached land. Or in other words, Cubans who were found at sea were returned to the communist island. This modification is also known as the wet-foot dry-foot policy. Further restrictions were also applied some including: 1) a limitation to the remittances sent to Cuba, 2) limit of the annual number of visas given to Cuban nationals, 3) placed several strict travel regulations to Cuba 4) placed a maximum of 20, 000 visas granted to Cuban nationals.
"Since then, Obama has lifted some restrictions on Cuba, allowing Cubans to visit family members and send more money back home. However, as underlined in the Helms Burton Act of 1996, the embargo will not be lifted until Cuba begins to become democratic."
Sample of Sources Used:
Banet-Weiser, S. (2003). Elian Gonzalez and "The Purpose of America": Nation, Family, and the Child-Citizen. American Quarterly. 55(2), 149-178.
Brannon, Rob. (2002). A wet and dry argument: Student groups say United States' policies towards immigration are inconsistent. The Oracle. Retrieved from http://www.usforacle.com/2.5741/a-wet-and-dry-argument-1.631801
Copeland, R. (1983). The Cuban Boatlift of 1980: Strategies in Federal Crisis Management. Anals of the American Academy of Political and Social Science. 467, 138-150.
DePalma, Anthony. (16 July, 1991). For Haitians, Voyage to a Land of Inequality. New York Times. Retrieved from http://www.usimmigrationsupport.org/cubanimmigration.html
Eckstein S., Barberia L.. (2002). Grounding Immigrant Generations in History: Cuban Americans and Their Transnational ties. International Migration Review. 36 (3), 799-837
Cite this Analytical Essay:
The Cuban Adjustment Act (2012, March 02) Retrieved July 19, 2019, from https://www.academon.com/analytical-essay/the-cuban-adjustment-act-150530/
"The Cuban Adjustment Act" 02 March 2012. Web. 19 July. 2019. <https://www.academon.com/analytical-essay/the-cuban-adjustment-act-150530/>
USDEURCAD
President Kennedy and the Cuban Missile Crisis
This paper offers an analysis of John F. Kennedy's decision-making during the Cuban missile crisis.
2 sources | 2004
The Patriot Act
A look at the controversial U.S.A. Patriot Act, which was enacted in response to the terrorist attack of September 11th.
New Deal law aimed at saving the farming economy. Looks at the background, provisions, politics, effects and problems.
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text:
module Shipper.Inputs (
    startFileInput,
    startZMQ4Input,
) where

import Shipper.Inputs.File
import Shipper.Inputs.ZMQ4

redpajama_set_name: RedPajamaGithub


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