text:
Multiunit Particulate Systems: A Current Drug-Delivery Technology
Pharmaceutical Technology, Pharmaceutical Technology-07-02-2011, Volume 35, Issue 7
The current review describes the role and selection of excipients, pellet core, coating materials, and compression with various cushioning agents.
Oral drug-delivery systems are the most acceptable form of controlled-release system to patients. Scientists have shown growing interest in modified-release oral dosage forms in recent years. Current technologies, such as oral multiparticulate drug-delivery systems (MDDS), have gained immensely in importance, not only because of their ability to control drug release, but also for the modified drug-release profiles they facilitate.
These systems release the drug with constant or variable release rates, thus maintaining drug concentration within the therapeutic window for a prolonged period of time. The desired release profile facilitates controlled absorption through the target site in the body, ensures good therapeutic activity, and reduces side effects (1). MDDS comprises a large number of small discrete particles (i.e., active ingredient and excipients), each demonstrating desirable features. They are prepared by methods including extrusion–spheronization, pelletization, granulation, spray drying, and spray congealing.
Multiunit particulate systems
Multiunit particulate systems (MUPS) are a novel MDDS technique for controlled and modified drug delivery. MUPS offer various advantages over other systems, including reduced risk of local irritation and toxicity, predictable bioavailability, reduced likelihood of dose dumping, minimized fluctuations in plasma concentration of drug, and high dose-strength administration (1). Multiparticulate systems show more reproducible pharmacokinetic behavior and lower intra- and intersubject variability than conventional (i.e., monolithic) formulations (2). Tableting of pellets reduces the esophageal residence time, compared with capsules, and improves physicochemical stability, compared with suspensions (2, 3).
The applications for which MUPS formulations are developed include taste masking (i.e., orodispersible MUPS tablets), enteric-release (e.g., of acid-labile drugs), and modified- or controlled-release orodispersible drugs for geriatric or pediatric patients. The technology of preparing compacted MUPS ensures that the desired objectives (e.g., taste masking coupled with orodispersibility as well as modified-release characteristics) are effectively achieved.
A good example of a MUPS is AstraZeneca's Losec, an antiulcer drug, the second-highest-selling pharmaceutical product in Sweden in 2002 (3). The product consists of microencapsulated drug granules tableted with excipients (4). Other marketed MUPS formulations include Galanil PR (Galantamine HBr) for Alzheimer's disease, antiobesity drug Lipidown (Orilistat), and Esomezol (Esomeprazole Sr) for erosive reflux esophagitis, which are all manufactured by Hanmi Pharmaceutical.
Challenges in the formulation of multiunit particulate systems
Each discrete particle in a MUPS product incorporates its own release characteristics and further contributes to the product's therapeutic activity. Compressing these subunits without affecting their individual release profiles is a major challenge of MUPS technology because compacting subunits may lead to structural changes in the coating and consequently alter drug-release behavior (5).
Other challenges for manufacturing pellets in tablets (i.e., MUPS) are weight variation, poor hardness, and friability. To prevent subunits from being altered, formulators include a cushioning agent (i.e., an excipient with protective properties) in the tablet formulation.
The compression-induced changes in the structure of the subunits may depend on numerous formulation factors, such as the type and amount of coating, the properties and structure of the substrate pellets, and the incorporation of excipient particles. During MUPS formulation, scientists must consider process variables such as the nature of the polymer; the shape, porosity, and density of pellets; compression force and content of coated pellets in the tableting blend; the wall thickness of coating; and the nature of the excipients.
Figure 1: Pelletization process. (FIGURE IS COURTESY OF THE AUTHOR)
Pelletization and multiunit particulate systems
Pellets are manufactured by both wet and dry granulation techniques or by layering. Extrusion–spheronization is a wet-granulation technique that helps in the preparation of pellets or spherical agglomerates. The process involves a blending stage, in which active ingredients are blended with excipients and mixed with suitable binding solutions to form a heavy plastic mass. This mass is subjected to extrusion to form extrudates of equal length. After extrusion, the materials undergo a spheronizing stage that rounds extrudates by cutting them and rolling them into spheres (see Figure 1).
Figure 2: Pelletized tablet with drug embedded polymer matrix system. (FIGURE IS COURTESY OF THE AUTHOR)
Manufacturers create modified-release systems in two main ways. They either coat spherical, uncoated pellets or embed a drug in a polymer matrix system (6). The uncoated drug–polymer pellets prepared by extrusion–spheronization are subjected to compression into tablets (see Figure 2). In another technique, the polymer or release-controlling material is coated along with the drug onto the uncoated pellet to form a nonpareil seed (see Figure 3). These drug–polymer coated pellets are compressed into tablets to obtain MUPS.
Figure 3: Pelletized tablet with polymer coated pellets. (FIGURE IS COURTESY OF THE AUTHOR)
Compressibility and compactibility
The ability of a powder to decrease in volume under pressure is called compressibility, and the ability of the powdered material to be compressed into a tablet of specific strength is called compactability (7). According to one theory, the compaction sequence for elastic materials includes particle rearrangement, plastic deformation, and elastic deformation (8). In Van der Zwan and Siskens's theory of the compaction of pellets, the process of volume reduction involves the filling of interparticle voids, where the secondary particles undergo readjustment; the fragmentation and plastic deformation of secondary particles; the filling of intraparticular voids, where primary particles rearrange, making the mass more dense; and the fragmentation and plastic deformation of the primary particles (9).
In an entirely different theory of compaction and volume reduction, Johansson stated that the secondary particles rearrange to fill interparticle voids where the strength of the compressed powder is too low due to low bonding force. Next, the surfaces of the secondary particles are flattened with local deformation. Then, as secondary particles undergo bulk deformation, they simultaneously become densely packed, and bonding strength increases significantly. Finally, low inter- and intragranular porosity causes the compression process to stop with less volume reduction of the bed but with higher bonding within the particles (10).
The major challenge of a formulator is to retain pelletproperties after the compaction process. To aid formulators, this article will describe the factors involved in the compaction and consolidation of coated and uncoated pellets.
Compression of coated pellets
Preparing compacted MUPS (i.e., compressing coated pellets to achieve multiple objectives) is a challenging task. During compaction, the polymeric coating may not withstand the compression force, thus affecting the surface of polymer and the pellets, which could cause the drug to be released in an undesired manner.
Hence, thorough process optimization is needed for the compaction of coated pellets. The main variables involved are the compression force and the velocity of the punches. The hardness, thickness, and porosity of the tablets must be maintained. Other important factors concerning the preparation of multiunit tablets are the properties of the barrier coating and the inclusion of protective excipient particles in the tablet formulation, and these parameters have been investigated extensively.
Pellet core. Many formulators have successfully studied and investigated the compression behavior of pellets consisting of various excipients. The selection and study of the material used to manufacture pellets is important to achieve the desired release pattern (11). The comparison between soft and hard pellets revealed that the pellets with soft constituents had the greater chance that intergranular pore spaces would be filled because the primary particles can move within the agglomerate. Harder pellets tend to fail at the surface because of the pressure of compaction.
Nicklasson studied the behavior of microcrystalline cellulose (MCC), alone and in combination with polyethylene glycol and dicalcium phosphate pellets, during and after compression. He concluded that pellets are deformed after compression, depending on their capacity for, mode of, and resistance to deformation. Nicklasson also studied polyethylene glycol as a cushioning agent to analyze the compression behavior of pellets. For the study, he used MCC-based beads loaded with theophylline, which are hard, and softer beads prepared with glyceryl monostearate (12).
Wang attempted to study the compression of lactose and MCC in various concentrations of powder and pellets. MCC-based pellets lost their plasticity during granulation and hence showed poor compactability, compared with lactose-based pellets (13). Iloanusi and Schwartz studied the crucial role that plastic deformation plays in compression by adding wax to the MCC bead formulations. Pellets with wax as a cushioning agent had more compressibility than beads without wax as a compression modifier (14).
Salako confirmed the advantages of softening materials during compression. On application of initial compaction pressure, the soft beads ruptured. On further application of pressure, the beads deformed and formed a network. Because of the soft nature of the beads, the material readily underwent deformation and rearrangement. Harder pellets are compact, and upon the application of compaction pressure, they underwent reduction in volume by particle rearrangement, not because of bond formation, compared with soft pellets (15).
Salako conducted a similar study of pellets' deformability and tensile strength using MCC-based beads loaded with theophylline, which are hard. Soft pellets were prepared with glyceryl monostearate (15).
Pellets undergo structural modifications during compaction. They need elasticity and flexibility to withstand compaction pressure. The ideal pellets are strong, not brittle, and have a low elastic resilience. They should deform under load application and load recovery without fracture (16). Knowledge of the compression behavior of uncoated pellets can provide a basis for the manufacture of multiunit tablets from barrier-coated pellets without damaging their coating.
Size and shape. Pellets undergo deformation after compression. Hence, the size of the pellets affects their compaction properties and the drug release from compacted pellets. Large pellets tend to undergo deformation more readily than small ones. Small pellets are stronger than large ones; they withstand compression pressure with less deformation (17). The strength of the pellets affects the final strength of the compressed tablet and helps ensure the desired release rate.
Johansson proposed that the deformation of individual pellets could be correlated with their size. A higher degree of deformation was observed with large pellets than with small pellets. As the size of pellets increased, the number of force-transmission decreased, which increased the contact force on each pellet (18). Isometric-shaped pellets offered fewer contact points and more uniform drug release than anisometric-shaped particles.
In addition to size, the shape of pellets affects the compression behavior and tablet-forming ability of granular materials. Irregular shapes induce complex compression behavior in granules. They increase the attrition of the granules, thus resulting in increased deformation (19–20). Flament found that, after the application of similar quantities of coating on pellets, small pellets were more fragile than large pellets. The probable reason is that small pellets' increased surface area reduced the film-coating thickness (21). Furthermore, increases in particle size resulted in more damage to the coating, as indicated by larger differences between the release profiles of tablets and uncompressed pellets (20).
Beckert compacted coated pellets of two crushing strengths with different excipients and concluded that the harder pellets were better able to withstand compression forces because they deformed to a lesser degree and their film coatings were less susceptible to rupture (22). Ragnarsson found that the compaction of small pellets had less effect on drug release than the compaction of large pellets. He also concluded, however, that the effect of pellet size depended on the choice of coating material, as well as on the amount and properties of the pellets and the excipients forming the tablet (23).
Density and porosity. Pellet density and size play an important role in achieving content and weight uniformity. Because of their intragranular porosity, pellets tend to densify. By modifying their intragranular porosity, manufacturers can deform and densify pellets during compression (24–27). Pellets with a narrow size distribution and excipients of similar sizes, shapes, and densities can prevent segregation (28). The critical density for achieving prolonged gastric residence may be between 2.4 and 2.8 g/cm3 (29). The amount and choice of material used for binding or granulating the powders during pelletization, and the compaction pressure, have a direct effect on the porosity.
Unlubricated pellets also require higher pressures than lubricated pellets (5). A study by Bodmeier revealed that an increased proportion of water as granulating fluid in the mixture led to hard and less porous tablets with a slow drug-release pattern. Similarly, pellets prepared using 95% ethanol as a granulating fluid showed good compressibility in contrast with pellets prepared with water (5). Using 95% ethanol during granulation formed strong intergranular bonds with an increased porosity, which finally increased the deformation of the formed pellets during compaction into tablets.
Porosity also can affect drug release. Tuton showed that pellets of high porosity were densely packed and deformed, and that the drug release from these pellets was not affected. But upon compaction of pellets with low porosity, the pellets were compressed with slight densification and deformation, leading to increased drug release. Using highly porous pellets did not alter the drug release after compression, in comparison with pellets with low porosity (30).
Compression force. Compression force is a critical parameter that must be optimized during tableting of pellets. Several studies investigated the compression force required for compressing pellets and found that 15 KN was sufficient for tablets with smooth surfaces. Flament studied the compression of theophylline-loaded pellets with acrylic polymer. Upon the application of compression pressure, the pellets were compacted by deformation at 6 KN. Further investigation revealed that increasing the compaction force to 20 KN did not alter the dissolution rate significantly (21).
Protective particles. Protective particles, also known as cushioning agents, help prevent damage to the drug–polymer-loaded core pellets. Protective particles rearrange themselves between the pellets and reduce the void space to prevent direct contact of pellets after the application of compression pressure. Preferred excipients are agglomerates (e.g., pellets or granules) that lower the risk that pellets will separate by size or density during processing, thus leading to weight variation or dose nonuniformity. When used as cushioning agents, primary particles (e.g., powder) give rise to the above problems (16, 21, 31). The cushioning effect of an excipient depends on its particle size, volume, and compaction properties. The method by which the particles undergo volume reduction needs to be studied. Several studies proved MCC and polyethylene glycol to be good excipients for compaction because of their plastic deformation (22, 32–34). Studies also proved that lactose, which undergoes fragmentation upon compression, offers better protection than MCC (35).
However, studies of 14 excipients proved that excipients that show good plastic deformation during compression give the best protection to the coating material (36). Particle size is an important factor in preformulation, and some studies suggested that particles smaller than 20 μm prevent damage to the coating. Increased dissolution rate was observed with particles bigger than 20 μm (29, 37). Using wax as a cushioning agent during pellet compression also is of great help to the formulator because it prevents damage to the coating during compression (38).
Nature of polymer. Polymers play an important part in any controlled- or modified-release dosage form. The final release of the drug from the formulation depends on the polymer used. A polymer must have appropriate plastic and elastic properties to withstand the shear of compression and compaction. Various polymers currently used to modify the release of pellets are either cellulosic polymers (e.g., ethyl cellulose) or acrylic polymers (e.g., Divakar's Polex, Evonik's Eudragit, or BASF's Kollicoat). The most frequently used polymers to extend the release of water-insoluble drugs are ethyl cellulose and ammonio methacrylate copolymers (39). Film-forming polymers have satisfactory elastic properties that prevent the rupture of the coating polymer, and good plastic properties that prevent deformation during compression.
Studies revealed that not only does the coating material affect compression properties, but also the solution in which polymer is dispersed or dissolved. The process entails dispersing polymer in water as pseudolatex or dissol-ving the polymer in an organic solvent. Investigations were conducted on ethyl cellulose to study its sustained-release properties after coating and compression in tablets. Ethyl cellulose improved pellets' puncture strength and elongation by making them brittle. The mechanical properties of ethyl cellulose were less affected after it was plasticized with pseudolatexes (19). Beads composed of alternating layers of ethyl cellulose, drug, and cushioning agent are less brittle than those that include only drug and ethyl cellulose.
Chang and Rudnic found that the solvent-based coatings were affected less by compression than the aqueous-based coatings were. Solvent-based coatings improved flexibility and mechanical stability in comparison with aqueous-based coatings (40). The coated pellets ruptured on compression, which affects the film formed on the pellets' surface.
To minimize or overcome rupture during compression, Bodmeier suggested placing the compressed pellets in a hot-air oven above their glass-transition temperature (5). The brittle and elastic properties of MCC pellets were modified by applying a water-based ethyl cellulose coating to them. Thus, plastoelastic properties were introduced to the pellets after coating, which improved their deformation characteristics (31).
Bechard and Celik showed that aqueous dispersions of ethyl cellulose for compression into multiunit tablets can, however, lead to coating failure through the formation of cracks and flaws (31–32). Films formed with high elasticity and apparent Newtonian viscosity delivered the maximum protection to the pellet core and coating on compaction (16). Lehmann suggested that the coating should be elongated at least 75% at the break to prevent the coating from rupturing during compression (41).
Thickness of polymer coating. The amount of coating affects how much compaction can modify it. Applying a thick polymeric coating to the surface of pellets imparts good elasticity and crushing strength to them (22). Damage to the coated pellets thus can be minimized during compression by applying a thick, rather than thin, coating of polymer solution (21–22). Bodmeier observed increased elastic and plastic deformation upon application of thick coating (5). The thickness of applied coatings provides good resistance to frictional forces, thus showing a direct dependence of cracks and elasticity on the film. To prevent the coatings from rupturing during compaction, the coating should have good elasticity and flexibility and be able to undergo structural changes and adapt to the deformation process (16, 22, 40, 41).
Plasticizer. Plasticizers are added to polymeric dispersions, especially to water-dispersions, to lower their glass-transition temperature and expedite the coalescence of the distinct polymer particles in the dispersion. Thus, coalescence of polymer particles directly relies on the time and temperature of coating and postcoating processes. Onions proposed a two-stage theory for the process of coalescence of aqueous polymeric dispersions.
The first stage includes the evaporation of the aqueous layer and the formation of a dry, transparent, apparently continuous film on the surface of the coated material. The coalescence of distinct polymer particles is completed gradually in the second stage. The water in the interstitial spaces starts evaporating slowly, bringing the separate particles close to each other and finally fusing the particles to form a strong and continuous film on the surface of the coated material (42–43). Further studies revealed that the amount of plasticizer did not influence drug release from compacted reservoir pellets (44). The flexibility of the aqueous-based coatings was improved by adding plasticizers, but Aulton observed that plasticizers led to a reduction in tensile strength (45). Felton proposed that increasing plasticizer content would increase the tensile strength of film-coated beads. The increased degree of plasticization of the polymer made the film more elastic and allowed it to withstand the deformation process during compression (46).
With its promising controlled-release mechanism for oral delivery, MUPS will be a focus of future research and development. The selection of excipients plays a key role in the success of MUPS. A thorough understanding of the factors that affect the performance of MUPS helps the formulator tailor the drug-release profiles. MUPS may soon become one of the most popular oral controlled-release systems.
Mitesh D. Phale* is a scientist and Abhijit V. Gothoskar is a global technical manager, both at Divakar Chemicals, 203–204, Sant Bhavan, Sharma Industrial Estate, Walbhat Rd., Goregaon–East, Mumbai 400 063, Maharashtra, India, phalemitesh@gmail.com.
*To whom all correspondence should be addressed.
1. N.S. Dey, S. Majumdar, and M.E.B. Rao, Trop. J. Pharm. Res. 7 (3), 1067–1075 (2008).
2. N. Follonier and E. Doelker, S.T.P. Pharma Sci. 2 (2), 141–158 (1992).
3. A.S. Abdul, A.V. Chandewar, and S.B. Jaiswal, J. Control. Release 147 (1), 2–16 (2010).
4. FASS 2002, A.G. Hedstrand, Ed. (LINFO, Stockholm, 2002), pp. 853–854.
5. R. Bodmeier, Eur. J. Pharm. Biopharm. 43 (1), 1–8 (1997).
6. A.E.K. Lundqvist, F. Podczeck, and J.M. Newton, Eur. J. Pharm. Biopharm. 46 (3), 369–379 (1998).
7. H. Leuenberger, Int. J. Pharm. 12 (1), 41–55 (1982).
8. C. Sun and D.J.W. Grant, Pharm. Dev. Technol. 6 (2), 193–200 (2001).
9. J. Van der Zwan and C.A.M. Siskens, Powder Technol. 33 (1), 43–54 (1982).
10. B. Johansson and G. Alderborn, Int. J. Pharm. 132 (1–2), 207–220 (1996).
11. J.B. Schwartz, N.H. Nguyen, and R.L. Schnaare, Drug Dev. Ind. Pharm. 20 (20), 3105–3129 (1994).
12. F. Nicklasson and G. Alderborn, Eur. J. Pharm. Sci. 9 (1), 57–65 (1999).
13. C. Wang et al., Drug Dev. Ind. Pharm. 21 (7), 753–779 (1995).
14. N.O. Iloanusi and J.B. Schwartz, Drug Dev. Ind. Pharm. 24 (1), 37–44 (1998).
15. M. Salako, F. Podczeck, and J.M. Newton, Int. J. Pharm. 168 (1), 49–57 (1998).
16. M.E. Aulton, A.M. Dyer, and K.A. Khan, Drug Dev. Ind. Pharm. 20 (20), 3069–3104 (1994).
17. J.L. Haslam et al., Int. J. Pharm. 173 (1–2), 233–242 (1998).
18. B. Johansson, F. Nicklasson, and G. Alderborn, Int. J. Pharm. 163 (1–2), 35–48 (1998).
19. N Sarisuta and K. Punpreuk, J. Control. Release 31 (3), 215–222 (1994).
20. S.C. Porter, Drug Dev. Ind. Pharm. 15 (10), 1495–1521 (1989).
21. M.P. Flament et al., Pharm. Technol. Eur. 6 (2), 19–25 (1994).
22. T.E. Beckert, K. Lehmann, and P.C. Schmidt, Int. J. Pharm. 143 (1), 13–23 (1996).
23. G. Ragnarsson et al., Drug Dev. Ind. Pharm. 13 (9–11), 1495–1509 (1987).
24. G.P. Millili and J.B. Schwartz, Drug Dev. Ind. Pharm. 16 (8), 1411–1426 (1990).
25. B. Johansson et al., Int. J. Pharm. 117 (1), 57–73 (1995).
26. F. Nicklasson and G. Alderborn, Pharm. Res. 17 (8), 947–952 (2000).
27. Y.S. Habib, L.L. Augsburger, and R.F. Shangraw, Int. J. Pharm. 233 (1–2), 67–83 (2002).
28. S.R. Bechard and J.C. Leroux, Drug Dev. Ind. Pharm. 18 (18), 1927–1944 (1992).
29. V.S.N.M. Dwibhasyam, Ind. J. Pharm. Sci. 70 (5), 555–564 (2008).
30. A. Tuton, J. Grasjo, and G. Alderborn, Eur. J. Pharm. Sci. 19 (5), 333–344 (2003).
31. M. Celik and L. Maganti, Drug Dev. Ind. Pharm. 20 (20), 3151–3173 (1994).
33. J.J. Torrado and L.L. Augsburger, Int. J. Pharm. 106 (2), 149–155 (1994).
34. H. Haubitz, W. Mehnert, and K.H. Fromming, Pharm. Ind. 58 (1), 83–86 (1996).
35. L. Stubberud et al., Pharm. Dev. Technol. 3 (2), 141–151 (1998).
36. H. Yuasa et al., S.T.P. Pharma Sci. 11 (3), 221–228 (2001).
37. T. Yao et al., Chem. Pharm. Bull. 46 (5), 826–830 (1998).
38. G.J. Vergote et al., Eur. J. Pharm. Sci. 17 (3), 145–151 (2002).
39. J. Hogan, "Coating of tablets and multiparticulates," in Pharmaceutics: The Science of Dosage Form Design, M.E. Aulton, Ed. (Churchill Livingstone, Edinburgh, 2002), pp.441–448.
40. R.K. Chang and E.M. Rudnic, Int. J. Pharm. 70 (3), 261–270 (1991).
41. K. Lehmann, H.U. Petereit, and D. Dreher, Pharm. Ind. 55 (10), 940–947 (1993).
42. A. Onions, Manuf. Chem. 57 (3), 55–59 (1986).
44. J.T. Heinamaki et al., Pharm. Ind. 57 (1), 68–71 (1995).
45. M.E. Aulton, Int. J. Pharm. Technol. Prod. Manuf. 3 (1), 9–16 (1982).
46. L.A. Felton et al., S.T.P. Pharma Sci. 7 (6), 457–462 (1997).
Drug DeliveryAnalyticsIngredientsFormulationManufacturingDevelopmentPharmaceutical Technology-07-02-2011
Bristol Myers Squibb and Century Therapeutics to Collaborate on Developing iPSC-derived Allogeneic Cell Therapies


text:
Journalist maimed in Lebanon blast
A prominent Lebanese journalist working for a leading anti-Syrian television station lost her left arm and leg when a bomb placed under her car exploded.
May Chidiac 40, is a presenter on LBC television (file)
Political talk show host May Chidiac of the private Lebanese Broadcasting Corporation was inside her car when the bomb exploded on Sunday in Ghadir, a town near the Christian port city of Jounieh, north of the capital, Lebanese security officials and the TV station said.
Chidiac was taken to Hotel Dieu Hospital in Beirut for surgery.
Late on Sunday, the hospital reported that Chidiac's left arm and leg were severed in the blast and her right leg and pelvis were broken.
A hospital statement said she was suffering from various injuries and burns all over her body, adding that her vital organs were "stable" but would need careful monitoring over the next few days.
The attack comes amid rising fears in Lebanon of security deterioration as UN investigation into the assassination former prime minister Rafiq al-Hariri nears conclusion. Two days ago, the UN investigators returned to Lebanon after four days of questioning Syrian officials in Damascus.
The country has been rife with rumors and speculation of more attacks as chief investigator Detlev Mehlis prepares to issue his report in late October.
Police officers inspect the damaged
car of May Chidiac in Jounieh
Prime Minister Fuad Siniora, speaking to reporters outside the hospital in Jounieh, said the bomb, like other recent explosions, was related to the al-Hariri investigation.
"There is no doubt it is all related, we don't want to deny that," Siniora said.
He appealed to Lebanese to be patient.
"We are paying the tax for freedom and independence," Siniora said, adding that he had contacted the US ambassador for technical assistance.
Under the driver's seat
A security official, speaking on condition of anonymity because he was not authorised to speak to the press, said the bomb was made up of less than two pounds of plastic explosives, placed under the driver's seat.
Television footage from the scene showed part of the car's left door was blown off. The front of the vehicle was a twisted wreck.
President Emile Lahoud denounced the attack and, in a statement, called for unity among the Lebanese.
Protests planned
Student unions called for sit-in protests at universities and in downtown Beirut on Monday.
"The country's security is exposed and anyone can fish (in the waters) and place bombs"
Druze politician Walid Jumblatt
Chidiac, who is in her 40s, is one of several hosts of a daily political talk show at the station, which broadcasts in Lebanon and is widely seen in the Arab world and by Lebanese communities across the world. Chidiac hosted the show Sunday morning with a political analyst from the leading An-Nahar newspaper.
LBC, a Christian TV station, is among the most prominent of anti-Syrian media outlets.
The explosion recalls a similar one on 2 June, when anti-Syrian journalist Samir Kassir was killed by a bomb placed under the seat of his car.
Accusations against Syria
Opponents of Syria's role in Lebanon have accused remnants of the Lebanese-Syrian intelligence apparatus of being behind the al-Hariri assassination and other bombings that targeted anti-Syrian personalities and shopping centers and industrial areas since then.
"There are remnants of the security apparatus who seem to be somewhere still causing security breaches. The country's security is exposed and anyone can fish (in the waters) and place bombs," said Druze politician Walid Jumblatt.
In an interview with LBC, Jumblatt called for the appointment of security officials to replace the arrested ones, appointments that have been held up by disputes among political groups within the government.
The UN mission to Syria added pressure on the Damascus government, which has been accused by opponents in Lebanon of involvement in al-Hariri's killing.
Syria denies any role in the assassination, which prompted a wave of anti-Syrian protests here and helped end Syria's almost three-decade domination of Lebanon.

redpajama_set_name: RedPajamaCommonCrawl


I want to say thank you to all of you who desire to encourage others with chronic illness! Living with EI, or any illness, is a continual battle against discouragement. Your show of love and support enables us to keep going. Thank you!
Some of my EI friends don't even own computers because of the EMF's. But they can handle short phone calls. Or with others, I write a letter on plain paper, using pencil, and then wrap it in aluminum foil to mail (to shield it from smells in transit). Other friends prefer to text or use FB.
Also, when trying to encourage, you need a balance of being a good listener with also not letting them go on and on about negative symptoms.
There's a time to let the person unburden their heart. In those moments you can simply listen and say "I love you, and I'll keep praying for you."
Then there are times when it's better to redirect the conversation away from negative thoughts to God's faithfulness or a positive topic. With chronic illness it's easy to continually rehearse physical symptoms or general complaints. Sometimes we need a friend to gently direct us to thanksgiving, trust, and praise.
However, especially for those with EI, gift-giving can be tricky. For a few years basically the only gifts I could receive were CD's or DVD's. I couldn't even read books for a while because of being sensitive to paper. And any product made in China caused serious reactions for me.
If you don't know what products the person can tolerate, then just ask. It's better to ask what they like and can use, than to try to send a "surprise" gift and cause them to have a reaction.
Also, gift cards are a wonderful option. To an EI person, a gift card is not "impersonal" - it's a treasure! Most of us have limited finances, so a gift card to Wal-mart, Amazon.com, NEEDS.com, or some other practical store is always appreciated.
For those not having EI, think about what they like and what kind of gifts will uplift them - perhaps a Christian fiction book, a funny movie, a beautiful journal they can write in, etc. It doesn't need to be expensive or elaborate. Small gifts are wonderful if there is thoughtfulness behind them.
One of my EI friends is a talented artist. When she has a little energy, she often makes cards for people out of her drawings. Another EI friend is a faithful prayer warrior for many people. Another one likes to write songs.
Well, I hope these tips are helpful for you. As you can see, showing love and support to those with chronic illness requires effort, getting to know the person and their needs, and relying on God's strength. But it's also a wonderful opportunity to be an expression of the love and grace of Jesus Himself. May we be His tangible presence in this hurting world.
Thanks! I pray they'll help a lot of people!


text:
Cléophas (Grec ancien: Κλεοπᾶς) est l'un des deux disciples de Jésus que ce dernier rencontra sur le chemin d'Emmaüs alors qu'ils revenaient de Jérusalem le soir de la Résurrection. Les deux disciples ne le reconnurent pas tout d'abord. Ils s'arrêtèrent ensemble dans une auberge et, pendant le repas, Jésus répéta les gestes de la consécration du pain : c'est alors qu'ils le reconnurent mais il disparut à leurs yeux. Aussitôt ils retournèrent vers Jérusalem où ils témoignèrent auprès des apôtres (évangile selon Luc 24,13-35).

Dans la tradition chrétienne, Cléophas ou Clopas est l'époux de Marie, l'une des Trois Maries. Avec elle, il a deux fils : Jacques le Mineur et Joset. C'est Marie Jacobé qui est présente près de la croix de Jésus dans les évangiles selon Marc et à selon Matthieu. Dans l'évangile selon Jean, elle est appelée « Marie femme de Clopas » (Jn 19:25), et il est précisé qu'elle est la sœur de Marie (mère de Jésus), mais les noms de ses fils ne sont pas mentionnés.

Cléophas est fêté le 25 septembre.

Annexes

Articles connexes
Clopas, autre personnage du Nouveau Testament .
Église Saint-Cléophas

Notes et références

Clopas

redpajama_set_name: RedPajamaWikipedia


Identification of new born baby's is one of the main tasks of the medical team following birth. Especially in developing countries , where security in public maternity wards is not very tight, and overcrowding is common, the risks of a baby swap or kidnap are above acceptable.
Reliable and fast methods for identification of new born baby's were made available and used inside maternity and hospitals, as well as on airports or bus stations.
New born baby's fingerprints cant be clearly captured , palm print recognition is not suitable for new born baby's yet since it is often difficult to let a newborn open his hand. Although the DNA examination is proven to be efficient in the univocal identification of individuals , but it comes at high cost and can't be used in real time applications , demanding sophisticated laboratory procedures.
Reduced size of the newborns ridges, which are three to five times smaller than on adults.
Image acquisition is fast , so reduces time for capturing footprint image.
More reliable than other types of newborns footprints identification.
If high resolution scanner used to scan ,greater resolution would yield better results.
ENROLLMENT : When a new baby born's , register that baby in the local database with the basic details and foot prints.
Enrollment ID :- a unique ID for baby.
Baby Name : – name of the baby.
Father Name : – baby's father name.
Date of Birth : baby's DOB.
Place :- baby's born place details .
Biometric Data : Take two captures of each foot .(Left foot 2 and right foot 2).
Click on "Enroll" button to save the data.
Matching : For Matching two different images of baby footprint taken . We can take this images directly from database or by live scan.
Click on "Match" button , to verify baby footprints.
Below is an eg. Where baby with name "qwe3r" is verified against his/her footprint .
One sample is loaded from database and other is taken using livescan.
In this article we presented a newborn footprint acquisition technique that uses a high-resolution optical sensor and provides very good identification rate.


text:
Our Campaigns, Right to Information
No Freedom of Information, threats a constant terror for whistleblowers instead
Malaysia is experiencing some kind of information warfare amidst an unstable government that places its political sustenance above the needs of the people.
This is to say that non-physical artillery in the form of (manipulated) information is actively being deployed to counter sensitive information that can discredit the government's public image and cause retaliation to destabilise its fragile administration.
From the start of November 2021, fellow Malaysians have been shocked by a series of allegations involving the upper echelons of powers within the Malaysian Anti-Corruption Commission (MACC) and the Royal Malaysian Police (PDRM).
Whistleblowing website Edisi Siasat implicated both the public institutions in a string of severe criminal activities and abuse of power allegations that ranged from top officers getting their hands soiled with drug trafficking to money laundering activities as well as PDRM's contribution to the proliferation of illegal gambling dens across Malaysia.
A week after the exposés, Edisi Siasat announced that dozens of mirror accounts had been created in its namesake to spread various versions of the release of its highly-incriminating original data. Subsequently, its Twitter account that amassed almost 100,000 followers was abruptly suspended.
Separately, following the publication of two damning articles (on Oct 28 and 29) by Malaysian anti-corruption activist Lalitha Kunaratnam — questioning the MACC — Asean-based website, the Independent News Services (INS), claimed malicious attempts had been made to disrupt their targeted server, service or network when attackers overwhelmed its surrounding infrastructure that it identified to be a distributed denial-of-service (DDoS).
Essentially, DDoS is a form of cyber attack which constitutes no less than a cyber crime where in the UK, offenders can be held liable to a prison sentence, a fine or both.
The INS articles intricately mapped out enormous stakes in commercial entities held by the incumbent and former chieftains of the MACC whose extensive network of allies included immediate members of their family as well as individuals acting as proxies in business deals.
What's deafeningly missing amidst these swirling allegations were responses by those mentioned to address the issue.
In light of the disclosures, the people's trust deficit towards both of these Malaysian law enforcement bodies had further tanked on top of the disrepute they have garnered as public institutions under the purview of the Ministry of Home Affairs and the Prime Minister's Department, potentially subjected to political interference.
Queries by opposition Parliamentarians regarding the issues were also egregiously shot down with curt replies not more than that of 'Investigations are underway', leaving Edisi Siasat and its equivalent compatriots to continue fending for themselves against the dark forces under hefty circumstances.
The unfolding of the saga further affirmed what has long been forewarned about by Tan Sri Dr Ramon Navaratnam, chairman of the Centre for Public Policy Studies at the Asian Strategy & Leadership Institute — that there exists a 'deep state' at work which keeps the masses ignorant of the reality facing the nation.
Information freedom paramount in times of crisis
Notwithstanding the above instances, the unsolicited disturbances faced by the legion of Malaysian whistleblowers in all aspects of the social fabric of Malaysian society further alludes to the absence of the Freedom of Information Act (FOIA) from the country's legislative system.
With a press industry under duress, further plagued by incessant layoffs in recent years, citizen journalists comprising ordinary citizens are increasingly wary of the narrowing space for crucial information to be disseminated. More have begun relying on the prevalence of social media to shed light on issues at a rate unseen in the past.
The Covid-19 pandemic alone saw dozens of whistleblowers proactively calling out empty-syringe vaccine administrators, errant unmasked politicians holding social gatherings and queue-jumping celebrities for vaccines on the public domain with the intent of compelling legal actions from the authorities.
At a time when the world is battling a deadly pandemic, the significance of having a free-flow of information to keep citizens aware of their surroundings is second to none and the FOI as a fundamental right to be prioritised at this juncture is beyond question.
An FOI legislation renders that all information held by governments and governmental institutions is in principle public, thereby safeguarding a transparent and accountable government that serves the people, and not the other way around.
Nevertheless, it is only clear by the day that the deliberate attempt at suppressing information and cold, hard data, paramount to reflect the real situation of the country, has been done largely to protect the vulnerability of the state and powers-that-be in the peak of this crisis.
People are beginning to feel the pinch as the Covid-19 pandemic plunged the nation into an acute economic crisis, signifying an urgent need for the people to rise in demand for justice where the setting-up of an FOIA can push for higher levels of public engagement in nation-building following increased openness.
Population kept in the dark exacerbates violation of rights
Alas! Malaysia, as a member of the United Nations which commits itself to upholding human rights internationally, regionally and within the country, has failed on a myriad of occasions to fulfil international standards of its obligations in various areas, one of which gravely concerns information freedom.
In hindsight, Malaysia has signed on to only three international human rights treaties — women, children and persons with disabilities — making it the only Asean country with the least number of international human rights treaties signed and ratified.
Since PN wrestled power from Pakatan Harapan in 2020, the administration fiercely exhibited unbridled propensity for curbing freedom of expression. Not much has changed with Datuk Seri Ismail Sabri's government either on its stance to 'bestow' Malaysia with the longstanding FOI law despite assurance from the Law Minister Datuk Seri Wan Junaidi Tuanku Jaafar on Nov 16 that the OSA will be reviewed.
Instead, in its place are a list of harsh laws being imposed against the masses to curb hard-hitting facts from ever surfacing, including interpretation of facts reported by news organisations that the government deems 'subversive' or challenge its (political) security.
Among such critical laws imposed against any public person for speaking up are the:
—Section 233 of the Communications and Multimedia Act (CMA) 1998 (concerning Improper use of network facilities or network service, etc)
— Official Secrets Act 1972 (OSA)
— Sedition Act 1948
— Emergency (Essential Powers) (No. 2) Ordinance 2021 (which shares many similarities with the repealed Anti-Fake News Act 2018)
— Printing Presses and Publications Act 1984
Case in point, the Malaysiakini court saga in early 2021 was a typical episode used as an example for muting public dissent and freedom of expression when the court ruled that Malaysiakini should be held in contempt over what were supposedly comments by its readers on an article published on June 9, 2020.
Media under siege
Concomitantly, free access to information is the key tool in combating corruption and wrongdoing. Investigative journalists and watchdog NGOs use this right to uncover information to expose wrongdoing and pursue resolutions for their disclosures.
However, media practitioners in Malaysia face insurmountable hostility in performing their duties. The country has seen scores of journalists being laid off in huge numbers in recent years and these events are sufficient indicators that also point to the dearth of local investigative journalists that are just as rare as hen's teeth, with only notable ones operating virtually from abroad, namely the Sarawak Report and the Wall Street Journal.
The latest blow to media freedom came on September 8, when media organisations critical of the government were excluded from the media list allowed to report on the Dewan Rakyat sitting on Parliament grounds.
Among those denied entry were the New Straits Times (NST), Utusan Malaysia, Kosmo, Harian Metro, Malay Mail, Free Malaysia Today, The Vibes, The Malaysian Insight, Malaysian Gazette and The Malaysian Reserve.
In an open letter, NST leaders questioned the rationale — or rather, the irrationality — of the decision stating: "For when those who are supposed to bear witness are blocked from doing their duty, democracy will crumble.
It added that as it is, Malaysia's ranking in the Reporters Without Borders' World Press Freedom Index 2021 has dropped to 119 this year, which is 18 ranks below 2020 when it stood at 101 out of 180 countries.
Adding to the challenges facing the media was PN's 'reincarnation' of the country's Anti-Fake News Act of 2018 (repealed in late 2019) in the form of the Emergency (Essential Powers) (No. 2) Ordinance 2021 that yielded a greater setback for press freedom. The law's decree enables the government to impose its own version of the truth which can spell trouble for an undiscerning audience that's susceptible to ethnocentric rhetoric.
Whistleblowers treading on dangerous waters
Not just that, principles of the FOI are challenged when Malaysia's whistleblower protection law itself is rigged with weaknesses. It is also regarded as inferior to the OSA.
For one, Section 6 (1) of the Whistleblower Protection Act 2010 (WBA 2010) concerns the disclosure of (public officers') improper conduct to any enforcement agency 'provided that such disclosure is not specifically prohibited by any written law'.
In this context, informants whose content of disclosure contravenes with either the OSA; the Banking and Financial Institutions Act (Bafia) 1989, which although was repealed in 2013, was used to charge whistle-blowing former Pandan MP Rafizi Ramli for disclosing banking information of several parties to the media; and also Section 203 (A) of the Penal Code, for instance, would criminalise them thus, outrightly crushing the rights of any whistleblower who comes forward with government revelation in the interest of the public.
Further to that, protection for whistleblowers, as outlined in the Act, would be revoked upon disclosure of knowledge to other parties apart from reporting it directly to the MACC. How then would whistleblowers come forward to lodge complaints involving enforcement officers or people in power, if even our public institutions are compromised in their integrity?
Therefore, all these events have implicitly scaled back any progress intended to be made for the advancement of the FOIA.
There are no better ways for the corrupt and powerful to escape prosecution when laws defeating their whole purpose are in place, while the lives of ordinary folks are taken for a gamble.
Are the people at the mercy of corruption?
Transparent governance means that government officials act openly, have nothing to hide from the people and its citizens are constantly kept abreast with all the decisions the government has to make.
But in Malaysia, after slipping six spots on the Transparency International Corruption Perception Index (CPI) 2020 (ranked 51st in 2019 to 57th in 2020) and with the state of corruption in our country breaching critical levels, the government must certainly have much to fear about coming clean with its act.
Which brings to question, is the country then at the mercy of a behemoth as vile as this widespread corruption threatening the security of our nation?
Just recently, Rasuah Busters leader Datuk Hussamuddin Yaacub cited the Global Financial Integrity Report 2017 on the whopping RM1.8 trillion lost between 2005 and 2014 due to corrupt practices in Malaysia which resulted in illicit financial flows. That, he added, are estimated losses of between RM40-60 billion per year due to graft!
We must, hereby, admit that in order to put the country back on track to flourish and prosper again, the war against corruption must be waged.
And, whether an FOIA is going to materialise in Malaysia or not would depend on the will of the political powers-that-be because ultimately, transparency through Freedom of Information is the weapon we have to use to win that war.
After all, Kofi Annan once said: "If corruption is the disease, transparency is an essential part of its treatment".
Center to Combat Corruption & Cronyism (C4 Center)
Join our Telegram channel to get our updates.
PrevOLDER POSTC4 Center Brief No. 2: Counting the Costs for Human Rights and the Environment
NEWER POSTC4 Center Research Project: Malaysia is not a "Garbage Dump"Next
Malaysian Whistleblowers


It hit the Pythagorean Brotherhood like an earthquake, a crisis of faith which shook the foundations of their universe. Some say Pythagoras himself made the dread discovery, others blame Hippasus of Metapontum.
Trying to learn about the secretive Pythagoreans is like wading into a swamp of myth and hearsay. But one thing we can't doubt: The group ran into a serious problem when someone tried to compare the diagonal of a square with its side.
Ratios are great for solving story problems.
According to Pythagoras, everything in the universe is made out of numbers. Which means the relationship between any two things — from musical notes to the sun and moon — can be described with a ratio.
But what was the ratio between the diagonal and the side?
Try to find two whole numbers such that .
We can easily put any ratio into lowest terms, so let's assume that our fraction x/y is in lowest terms. This is important, as you will see.
The product is obviously an even number. Only even numbers are even when squared, so we know that must also be an even number.
And since our fraction x/y was in lowest terms, it naturally follows that has to be an odd number.
But cannot be both odd and even — it's impossible!
Therefore, our original assumption must be wrong. There is no ratio .
That means we can never calculate the exact value of . Today we call numbers like irrational (not ratio-nal). Another famous irrational number is the circle constant .
To the Pythagoreans, however, there had to be a ratio. If there were no ratio, then couldn't be made of whole numbers, and everything was made of numbers. Wasn't it?
It was enough to drive a mathematical cultist crazy.
Read all the posts from the March/April 1999 issue of my Mathematical Adventures of Alexandria Jones newsletter.
This is a great story, and a deservedly famous proof, one of the best proofs ever in my opinion.
I used to think my students understood it. Then one year I did this proof in class, asked them to use the same method to prove that the square root of 3 is irrational for homework, which they did … and then asked them to use the same method to prove that the square root of 4 is irrational on the test … and most of them did. I think if a student can't find the flaw in using the same proof to prove that the square root of four is irrational, then they don't really understand the proof. Your explanation here is very good, so I'd give your students above average chances of figuring it out.
How funny! If I get enough students for a high school class at our co-op next year, I will definitely have to try that.
I find it tough to justify that we can just assume a/b is reduced thereby creating the setup that one of them has to be odd. It is a little too convenient that the only thing proving root two to be irrational here is that it contradicts the assumption. We do not use the assumption to generate the contradiction, only test ourselves in the end against our assumption.
I did try to prove that root 4 was irrational just as a test and I unfortunately got to the conclusion that b=a/2, which is what one would expect.
In university I did used to be confident in a form of this proof, which did rely on proving that a number was both even and odd. I'll try to find the more pleasing version to me.
Can't any fraction be reduced to lowest terms without loss of generality? If diagonal/side can be written as a ratio of natural numbers, then it must have a lowest-terms equivalent. We just assume from the beginning that a/b (or x/y, as I used in my article) is that lowest-terms equivalent.
In your proof that there is no largest prime, you may want to point out that the number constructed will not always be prime itself. 31 is prime, but if your list of primes had started out as 2 and 7, you would have constructed the number 15. That is not prime, which would tell you there is at least one prime number less than 15 that is not in your set.
Assuming something and then proving it later is called Mathematical Induction, and it is widely used in mathematics. It is a little hard to grasp sometimes, but when you do grasp it it makes sense.
* then it must be true for all natural numbers.
But assuming something and then proving it later — whatever that technique might be called — is certainly a useful trick for some problems, as long as one does actually come back and prove it. Usually my students want to just assume and leave it at that.
Pingback: Renée's Platonic Mobile « Let's Play Math!
Irrational numbers are also rational because we can speculate about objects with irrational sizes, for example, we can speculate about circumference with irrational length or about square with a diagonal of irrational length, but they are ideal, because in reality does not exist object with irrational size.
Length of the real circumference will never be equal to the length of a perfect circumference, and length of diagonal of a real square will never be equal to the length of diagonal of a ideal square.
Therefore, there will not be a problem of squaring the circle and a problem of incommensurability of the side and diagonal of the real square.
Incommensurability problem is just for ideal square.
Therefore irrational numbers should be renamed in ideal numbers, and rational numbers should be renamed in real numbers.
The set of real and ideal numbers will together constitute the set of rational numbers (for mathematics needs), but only real numbers (ex-rational) will be needed in practice.
Terminology grows from history, and it's not easy to change after it's established. The words "rational" and "irrational" seem pretty well settled to me. Students always have trouble remembering them at first, but the connection to "ratio" provides an opportunity to review that fundamental concept.
I'm not sure your suggested terms are an improvement. There is no perfect "2" in the real world, either — all numbers are "ideal" in that sense. Real world measurement is always an approximation, even if you use an electron microscope. But math lives in the ideal world of imagination, where both 2 and its square root are equally real.


text:
Build-A-Bear Workshop:
Springtime Surprises: New "Scratch & Match" Gifts with Purchase, Scrambles™ Mix 'n' Match Gifts and In-store Activities in Bloom at Build-A-Bear Workshop®
By: Build-A-Bear Workshop | 0 Shares 14 Reads
ST. LOUIS, April 11, 2019 // PRNewswire // - Build-A-Bear® is hatching a spring full of fun for every-bunny, including the opportunity to bring home FREE gifts with the purchase of furry friends, new creative collections to complete every Easter basket, and an in-store scavenger hunt - plus, Easter photo ops for the family.
Fun and Games: Gifts with Purchase and Events at the Workshop
Beginning tomorrow, April 12, Guests who visit any Build-A-Bear Workshop® location will receive a free Spring Surprise Scratch & Match card with the purchase of a furry friend, while supplies last. Upon receiving the card, participants can scratch to reveal a free-gift offer valid with a furry friend purchase. Surprises can include a free heartbeat, scent, furry-friend T-shirt or reusable drawstring backpack, while supplies last. Full details and a disclaimer for Spring Surprise Scratch & Match are available at buildabear.com/events.
Additionally, on weekends in April, families can hop into the Workshop for a free in-store Easter-egg token scavenger hunt, as well as a photo opportunity with the Build-A-Bear bunny mascot, Pawlette™! Pawlette will be available for photos on Saturday, April 13 and Saturday, April 20 at 12 p.m. in all time zones.
More details on springtime events at the Workshop can be found at buildabear.com/events.
Egg-hunt Finds: Spring Furry Friends + New Scrambles™ by Build-A-Bear
For those on the hunt for Easter gifts to complete their basket, several new 16-inch bunny furry friends are available in stores and online at buildabear.com, as well as colorful coordinating outfits, accessories and pre-stuffed gift sets. New 8-to-9-inch springtime Build-A-Bear Buddies™ are the perfect furry friends for taking along on Easter-egg hunts - and they fit right in the plush Easter Basket Accessory!
Gift-givers can mix up the Easter baskets this year with a slew of furry friends, plus the all-new Scrambles™ by Build-A-Bear! Available in stores only, Scrambles toy eggs come with a special, smiley 3-inch friend inside - from a unicorn to a puppy to a bear or bunny - plus, separate hands, feet and accessories for mix 'n' match creations. Collectors can scramble the pieces from all their Scrambles eggs to make fun new friends each time.
For the perfect (sugar-free) spring treat, Guests can now make their own Dylan's Candy Bar® Bear in Build-A-Bear Workshop stores and at buildabear.com - and add colorful Dylan's Candy Bar outfits and fun accessories, such as a Dylan's Candy Bar Pajama Set or Dylan's Candy Bar Whirly Pop® Wristie! This is the first time Build-A-Bear Workshop and Dylan's Candy Bar have teamed up to offer a collaborative collection that seeks to inspire creativity, heart, and the inner child in everyone - which is central to the missions of both brands.
Hop in to Give "Hugs N' Hope" to Children in Need
To further the company's mission to add a little more heart to life, Build-A-Bear and Build-A-Bear Foundation™ are continuing to offer Guests the opportunity to help share comfort and hugs by making their own limited-edition Hugs N' Hope Bear in stores or online. For every Hugs N' Hope Bear sold - while supplies last - Build-A-Bear will donate one teddy bear to Build-A-Bear Foundation to be given to a child in need.
Fans can stay tuned to the brand's social media channels for Build-A-Bear Foundation updates, and visit buildabear.com/giving for more information on Build-A-Bear's charitable giving efforts.
About Build-A-Bear®
Build-A-Bear® is a global brand kids love and parents trust that seeks to add a little more heart to life. Build-A-Bear Workshop® has over 450 stores worldwide where Guests can create customizable furry friends, including corporately-managed stores in the United States, Canada, China, Denmark, Ireland, Puerto Rico, and the United Kingdom, and franchise stores in Africa, Asia, Australia, Europe, Mexico and the Middle East. Buildabear.com is the online destination for unique furry-friend gifts, featuring The-Bear-Builder™, a shopping configurator that helps create customized gift options. Build-A-Bear Workshop, Inc. (NYSE: BBW) posted a total revenue of $336.6 million in fiscal 2018.
About Build-A-Bear Foundation™
Build-A-Bear® believes in the power of hugs and the simple comfort of having a furry friend by your side. Since 1997, Build-A-Bear and Build-A-Bear Foundation™ have donated more than $50 million to a variety of organizations and in a number of ways. The mission of Build-A-Bear Foundation is to add a little more heart to life by sharing hugs and making days a little bit brighter for those in need. The Foundation is committed to sharing teddy-bear hugs with nonprofit organizations and registered charities that support the well-being of children in areas where Build-A-Bear Guests and associates live, work and play. For more information, visit buildabear.com/giving.
About Dylan's Candy Bar®
Bar Dylan's Candy Bar was founded in 2001 by Dylan Lauren with a mission to awaken the creative spirit and inner child in everyone. Renowned for merging the worlds of art, fashion and pop culture with candy, Dylan's Candy Bar is the pioneer in changing the way we see candy today. As the largest state-of-the-art sweets emporium and candy lifestyle brand, Dylan's Candy Bar is not your average "candy store." The modern day candy land is home to over 7,000 candies from around the world, making it the most popular destination for the ultimate sugar rush experience.
Dylan's Candy Bar freestanding stores are currently located in New York City at 60th Street and in Union Square; Chicago; Los Angeles; Miami and East Hampton. In addition to luxury boutiques in premier hotels, international airports and leading department stores, Dylan's Candy Bar plans to continue expanding in major cosmopolitan cities in the U.S. and worldwide.
For more information about Dylan's Candy Bar, visit www.DylansCandyBar.com. Follow them on Facebook, Twitter, Instagram and Pinterest @DylansCandyBar
Maria Lemakis
marial@buildabear.com
Cision View original content to download multimedia:http://www.prnewswire.com/news-releases/springtime-surprises-new-scratch--match-gifts-with-purchase-scrambles-mix-n-match-gifts-and-in-store-activities-in-bloom-at-build-a-bear-workshop-300830494.html
SOURCE Build-A-Bear
Founded in St. Louis in 1997, Build-A-Bear, a global brand kids love and parents trust, seeks to add a little more heart to life.
Franchise News Room »
News By Industry »
Meineke Car Care Centers
Meineke Car Care Centers is a leader in the automotive aftermarket, providing high-quality, low-cost under-car repair services at more than 800...
Beverly Hills Rejuvenation Center
Beverly Hills Rejuvenation Center (BHRC) provides the highest quality medical spa services to our clients in a comfortable and supportive...
Fantastic Sams
Fantastic Sams® is one of the most recognized brands in the hair care industry with nearly 1,200 full-service salons in North America and 40 years...
HomeWell Cares
An Opportunity Like No Other; where personal fulfillment meets financial success.
Venture X
The coworking market is entering a new growth phase - join in on it by opening a Venture X coworking franchise. Learn all about the opportunity.


text:
Joan Fa, né le , à Barcelone, en Espagne, est un ancien joueur espagnol de basket-ball.

Biographie

Palmarès
 Champion d'Espagne 1967

Notes et références

Liens externes

Joueur international espagnol de basket-ball
Joueur de la Joventut Badalona
Naissance en décembre 1943
Naissance à Barcelone


4 X 1 US Gallon box. Rust Bullet Metal Blast Rust Dissolver, Surface Cleaner and Conditioner: provides superior bonding properties to surfaces with poor adhesive qualities.
Rust Bullet Metal Blast Rust Dissolver, Surface Cleaner and Conditioner. Rust Bullet Metal Blast is a cleaner and conditioner for metal that will provide superior bonding properties to surfaces with poor adhesive qualities. Metal Blast will remove surface rust and properly etch the metal for better paint adhesion. Metal Blast enhances the adhesive properties of all Rust Bullet Coatings on any surface including aluminium and shiny polished metal surfaces. Metal Blast delivers years of extra performance to any paint project.
4 X 1 Gallon box special saver deal. BUY NOW! Limited time offer.


text:
Daily Ratings & News for Capri
Complete the form below to receive the latest headlines and analysts' recommendations for Capri with our free daily email newsletter:
Frontier Capital Management Co. LLC Acquires New Position in Capri Holdings Ltd (CPRI)
Posted by Austin De'Marion on May 17th, 2019
Frontier Capital Management Co. LLC acquired a new stake in shares of Capri Holdings Ltd (NYSE:CPRI) during the first quarter, according to the company in its most recent disclosure with the Securities & Exchange Commission. The firm acquired 1,330,780 shares of the company's stock, valued at approximately $60,883,000.
Several other institutional investors and hedge funds also recently bought and sold shares of the stock. Geode Capital Management LLC acquired a new stake in Capri in the 4th quarter worth about $89,438,000. Janus Henderson Group PLC acquired a new stake in Capri in the 1st quarter worth about $43,256,000. Teacher Retirement System of Texas acquired a new stake in Capri in the 1st quarter worth about $41,733,000. Robeco Institutional Asset Management B.V. acquired a new stake in Capri in the 1st quarter worth about $33,653,000. Finally, Systematic Financial Management LP acquired a new stake in Capri in the 1st quarter worth about $30,418,000. 78.76% of the stock is currently owned by institutional investors and hedge funds.
Get Capri alerts:
A number of brokerages have issued reports on CPRI. Zacks Investment Research raised Capri from a "hold" rating to a "buy" rating and set a $47.00 price target on the stock in a research note on Wednesday, May 8th. Barclays began coverage on Capri in a research note on Tuesday, February 26th. They issued an "overweight" rating and a $53.00 price target on the stock. ValuEngine raised Capri from a "strong sell" rating to a "sell" rating in a research note on Friday, February 8th. Guggenheim reaffirmed a "hold" rating on shares of Capri in a research note on Wednesday, February 6th. Finally, Needham & Company LLC reduced their price objective on Capri from $67.00 to $61.00 and set a "buy" rating on the stock in a research note on Friday, February 1st. One research analyst has rated the stock with a sell rating, two have issued a hold rating and six have assigned a buy rating to the stock. Capri presently has an average rating of "Buy" and a consensus price target of $58.29.
NYSE CPRI opened at $40.28 on Friday. The stock has a market capitalization of $6.06 billion, a PE ratio of 8.91, a PEG ratio of 1.22 and a beta of 0.47. Capri Holdings Ltd has a 1-year low of $35.68 and a 1-year high of $75.96. The company has a current ratio of 2.48, a quick ratio of 1.93 and a debt-to-equity ratio of 0.86.
TRADEMARK VIOLATION WARNING: "Frontier Capital Management Co. LLC Acquires New Position in Capri Holdings Ltd (CPRI)" was originally posted by Macon Daily and is owned by of Macon Daily. If you are accessing this report on another site, it was illegally stolen and republished in violation of United States & international trademark & copyright law. The legal version of this report can be read at https://macondaily.com/2019/05/17/frontier-capital-management-co-llc-acquires-new-position-in-capri-holdings-ltd-cpri.html.
Capri Company Profile
Capri Holdings Limited design, markets, distributes, and retails branded women's and men's apparel and accessories. It operates in four segments: MK Retail, MK Wholesale, MK Licensing, and Jimmy Choo. The MK Retail segment sells women's apparel; handbags and small leather goods; men's apparel; footwear; and licensed products comprising watches, jewelry, fragrances, and beauty and eyewear.
Featured Story: Why do companies issue convertible shares?
Want to see what other hedge funds are holding CPRI? Visit HoldingsChannel.com to get the latest 13F filings and insider trades for Capri Holdings Ltd (NYSE:CPRI).
Receive News & Ratings for Capri Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Capri and related companies with MarketBeat.com's FREE daily email newsletter.
Quinn Opportunity Partners LLC Takes $497,000 Position in Teekay Co. (TK)
iShares Core MSCI EAFE ETF (IEFA) Shares Bought by MCF Advisors LLC


Marietta Waters is an American vocalist, born and raised in the Philadelphia area. Singing was a way of life in her musically talented family.
Both of Marietta's parents were professional entertainers–Mary Waters a dancer and Arthur J. Waters a pianist.
As a child, Marietta loved to sing and perform with her parents on stage. In the years to follow she evolved into a successful solo singer, songwriter, producer, and vocal coach.
Marietta's solo career flourished in the post-disco eighties era. Under the name Marietta she released several singles and appeared on movie soundtracks for several top grossing films, including Top Gun and Fire & Ice.
In an enviable career spanning four decades, Marietta toured and recorded with a number of top musical artists. The long list includes Sergio Mendes, Oscar Castro-Neves, Harold Faltermeyer, Giorgio Moroder, Berlin, Animotion, Donna Summer, Elton John, Olivia Newton-John, Crystal Lewis, Dave Grusin, Cyndi Lauper, The Cars, Huey Lewis, Jeffrey Osborne, Lee Ritenour, Ringo Starr, Tony Bennett, Stevie Wonder, and Maurice White and Verdine White of Earth, Wind & Fire.
Marietta has a special voice that transcends musical styles.
Marietta's latest release was inspired by her pop, soul, Latin, jazz, R&B, and gospel influences.
Now living in southern California, Marietta continues to work as a songwriter, performer, recording artist, and singing coach.


Anthony & Jessica –Wedding Photography– A wedding can be summed up as wealth of emotions that have developed over a lifetime of experiences that comes to this destination in this moment and time. It provides the definition of a mother and her daughter, the anticipation of a first look or reveal and the tears of joy of a life that will be. Anthony & Jessica, their family and friends provided all this and more!
And a special thanks to Matt in capturing some incredible photos all day.
Plymouth Grand Opening – Today is the Day!


text:
Transition to invasive breast cancer is associated with progressive changes in the structure and composition of tumor stromaRisom, et al., BioRxiv Jan 2021
Abstract: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that is thought to be a precursor to invasive breast cancer (IBC). To understand how the tumor microenvironment (TME) changes with transition to IBC, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and a 37-plex antibody staining panel to analyze 140 clinically annotated surgical resections covering the full spectrum of breast cancer progression. We compared normal, DCIS, and IBC tissues using machine learning tools for multiplexed cell segmentation, pixel-based clustering, and object morphometrics. Transition from DCIS to IBC was found to occur along a trajectory marked by coordinated shifts in location and function of myoepithelium, fibroblasts, and infiltrating immune cells in the surrounding stroma. Taken together, this comprehensive study within the HTAN Breast PreCancer Atlas offers insight into the etiologies of DCIS, its transition to IBC, and emphasizes the importance of the TME stroma in promoting these processes.
Risom, et al., BioRxiv Jan 2021
doi: https://doi.org/10.1101/2021.01.05.425362
Multiplexed single-cell metabolic profiles organize the spectrum of cytotoxic human T cellsHartmann, et al., Nat. Biotechnology Aug 2020
Abstract: Cellular metabolism regulates immune cell activation, differentiation and effector functions to the extent that its perturbation can augment immune responses. However, the analytical technologies available to study cellular metabolism lack single-cell resolution, obscuring metabolic heterogeneity and its connection to immune phenotype and function. To that end, we utilized high-dimensional, antibody-based technologies to simultaneously quantify the single-cell metabolic regulome in combination with phenotypic identity. Mass cytometry (CyTOF)-based application of this approach to early human T cell activation enabled the comprehensive reconstruction of the coordinated metabolic remodeling of naïve CD8+ T cells and aligned with conventional bulk assays for glycolysis and oxidative phosphorylation. Extending this analysis to a variety of tissue-resident immune cells revealed tissue-restricted metabolic states of human cytotoxic T cells, including metabolically repressed subsets that expressed CD39 and PD1 and that were enriched in colorectal carcinoma versus healthy adjacent tissue. Finally, combining this approach with multiplexed ion beam imaging by time-of-flight (MIBI-TOF) demonstrated the existence of spatially enriched metabolic neighborhoods, independent of cell identity and additionally revealed exclusion of metabolically repressed cytotoxic T cell states from the tumor-immune boundary in human colorectal carcinoma. Overall, we provide an approach that permits the robust approximation of metabolic states in individual cells along with multimodal analysis of cell identity and functional characteristics that can be applied to human clinical samples to study cellular metabolism how it may be perturbed to affect immunological outcomes.
Hartmann, et al., Nat. Biotechnol. 31 Aug 2020: s41587-020-0651-8
Single-nucleus and spatial transcriptomics of archival pancreatic cancer reveals multi-compartment reprogramming after neoadjuvant treatmentHwang, et al., BioRxiv Aug 2020
Abstract: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory disease. Characterizing PDAC by mRNA profiling remains particularly challenging. Previously identified bulk expression subtypes were influenced by contaminating stroma and have not yet informed clinical management, whereas single cell RNA-seq (scRNA-seq) of fresh tumors under-represented key cell types. Here, we developed a robust single-nucleus RNA-seq (snRNA-seq) technique for frozen archival PDAC specimens and used it to study both untreated tumors and those that received neoadjuvant chemotherapy and radiotherapy (CRT). Gene expression programs learned across untreated malignant cell and fibroblast profiles uncovered a clinically relevant molecular taxonomy with improved prognostic stratification compared to prior classifications. Moreover, in the increasingly-adopted neoadjuvant treatment context, there was a depletion of classical-like phenotypes in malignant cells in favor of basal-like phenotypes associated with TNF-NFkB and interferon signaling as well as the presence of novel acinar and neuroendocrine classical-like states, which may be more resilient to cytotoxic treatment. Spatially-resolved transcriptomics revealed an association between malignant cells expressing these basal-like programs and higher immune infiltration with increased lymphocytic content, whereas those exhibiting classical-like programs were linked to sparser macrophage-predominant microniches, perhaps pointing to susceptibility to distinct therapeutic strategies. Our refined molecular taxonomy and spatial resolution can help advance precision oncology in PDAC through informative stratification in clinical trials and insights into differential therapeutic targeting leveraging the immune system.
Hwang, et al., BioRxiv 25 Aug 2020: 10.1101/2020.08.25.267336
PREPRINT doi: 10.1101/2020.08.25.267336
Multimodal analysis of composition and spatial architecture in human squamous cell carcinomaJi, et al., Cell Jul 2020
Abstract: To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), Ji et al. combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging (MIBI, a multiplexed spatial proteomics platform) from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.
Ji, et al., Cell (2020) July 23
Multiplexed imaging of human tuberculosis granulomas uncovers immunoregulatory features conserved across tissue and bloodMcCaffrey, et al., BioRxiv Jun 2020
Abstract: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that is distinctly characterized by granuloma formation within infected tissues. Granulomas are dynamic and organized immune cell aggregates that limit dissemination, but can also hinder bacterial clearance. Consequently, outcome in TB is influenced by how granuloma structure and composition shift the balance between these two functions. To date, our understanding of what factors drive granuloma function in humans is limited. With this in mind, we used Multiplexed Ion Beam Imaging by Time-of-Flight (MIBI-TOF) to profile 37 proteins in tissues from thirteen patients with active TB disease from the U.S. and South Africa. With this dataset, we constructed a comprehensive tissue atlas where the lineage, functional state, and spatial distribution of 19 unique cell subsets were mapped onto eight phenotypically-distinct granuloma microenvironments. This work revealed an immunosuppressed microenvironment specific to TB granulomas with spatially coordinated co-expression of IDO1 and PD-L1 by myeloid cells and proliferating regulatory T cells. Interestingly, this microenvironment lacked markers consistent with Tcell activation, supporting a myeloid-mediated mechanism of immune suppression. We observed similar trends in gene expression of immunoregulatory proteins in a confirmatory transcriptomic analysis of peripheral blood collected from over 1500 individuals with latent or active TB infection and healthy controls across 29 cohorts spanning 14 countries. Notably, PD-L1 gene expression was found to correlate with TB progression and treatment response, supporting its potential use as a blood-based biomarker. Taken together, this study serves as a framework for leveraging independent cohorts and complementary methodologies to understand how local and systemic immune responses are linked in human health and disease.
PREPRINT – McCaffrey, et al., BioRxiv (2020) June 09
MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structureKeren, et al., Science Advances Oct 2019
Abstract: Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements. We image fields of view up to 800 μm × 800 μm at resolutions down to 260 nm with sensitivities approaching single-molecule detection. We leverage these properties to interrogate intrapatient heterogeneity in tumor organization in triple-negative breast cancer, revealing regional variability in tumor cell phenotypes in contrast to a structured immune response. Given its versatility and sample back-compatibility, MIBI-TOF is positioned to leverage existing annotated, archival tissue cohorts to explore emerging questions in cancer, immunology, and neurobiology.
Keren, et al., Science Advances 09 Oct 2019: 5(10), eaax5851
doi: 10.1126/sciadv.aax5851
Tissue imaging by mass spectrometry: a practical guide for the medicinal chemistJohnson, et al., ACS Medical Chemistry Letters Jan 2019
Abstract: Understanding the tissue distribution of therapeutic molecules is often critical for assessing their efficacy and toxicity. Unfortunately, standard methods for monitoring localized drug distribution are resource-intensive and are typically performed late in the discovery process. As a result, early development efforts often progress without detailed information on the effect that changes in structure and/or formulation have on drug localization. Recent innovations in mass spectrometry (MS) provide new options for mapping the spatial distribution of drug in tissue, and allow parallel detection of endogenous species. These advances are improving access to drug distribution data early in discovery, and provide insight into local biochemical changes that are directly related to drug activity. The literature on these topics is voluminous and the technology is advancing rapidly, offering a bewildering array of options for researchers who are new to the field. To guide medicinal chemists who wish to apply these methods in their research, this technology perspective provides our views on practical applications that are currently enabled by various MS imaging (MSI) approaches, along with recommendations for how best to implement these methods in pharmaceutical R&D.
Johnson et al. ACS Medical Chemistry Letters. January, 2019
A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imagingKeren, et al, Cell Sept 2018
Abstract: The immune system is critical in modulating cancer progression, but knowledge of immune composition, phenotype, and interactions with tumor is limited. We used multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to simultaneously quantify in situ expression of 36 proteins covering identity, function, and immune regulation at sub-cellular resolution in 41 triple-negative breast cancer patients. Multi-step processing, including deep-learning-based segmentation, revealed variability in the composition of tumor-immune populations across individuals, reconciled by overall immune infiltration and en-riched co-occurrence of immune subpopulations and checkpoint expression. Spatial enrichment analysis showed immune mixed and compartmentalized tumors, coinciding with expression of PD1, PD-L1, and IDO in a cell-type- and location-specific manner. Ordered immune structures along the tumor-immune border were associated with compartmentalization and linked to survival. These data demonstrate organization in the tumor-immune microenvironment that is structured in cellular composition, spatial arrangement, and regulatory-protein expression and provide a framework to apply multiplexed imaging to immune oncology.
Keren et al. Cell, Volume 174, Issue 6, P1373-1387. E19. September 06, 2018
Multiplexed ion beam imaging analysis for quantitation of protein expression in cancer tissue sectionsRost, et al., Lab. Invest. Aug 2017
Abstract: Part of developing therapeutics is the need to identify patients who will respond to treatment. For HER2-targeted therapies, such as trastuzumab, the expression level of HER2 is used to identify patients likely to receive benefit from therapy. Currently, chromogenic immunohistochemistry on patient tumor tissue is one of the methodologies used to assess the expression level of HER2 to determine eligibility for trastuzumab. However, chromogenic staining is fraught with serious drawbacks that influence scoring, which is additionally flawed due to the subjective nature of human/pathologist bias. Thus, to advance drug development and precision medicine, there is a need to develop technologies that are more objective and quantitative through the collection and integration of larger data sets. In proof of concept experiments, we show multiplexed ion beam imaging (MIBI), a novel imaging technology, can quantitate HER2 expression on breast carcinoma tissue with known HER2 status and those values correlate with pathologist-determined IHC scores. The same type of quantitative analysis using the mean pixel value of five individual cells and total pixel count of the entire image was extended to a blinded study of breast carcinoma samples of unknown HER2 scores. Here, a strong correlation between quantitation of HER2 by MIBI analysis and pathologist-derived HER2 IHC score was identified. In addition, a comparison between MIBI analysis and immunofluorescence-based automated quantitative analysis (AQUA) technology, an industry-accepted quantitation system, showed strong correlation in the same blind study. Further comparison of the two systems determined MIBI was comparable to AQUA analysis when evaluated against pathologist-determined scores. Using HER2 as a model, these data show MIBI analysis can quantitate protein expression with greater sensitivity and objectivity compared to standard pathologist interpretation, demonstrating its potential as a technology capable of advancing cancer and patient diagnostics.
Rost et al., Lab Invest. 2017 Aug;97(8):992-1003
doi: 10.1038/labinvest.2017.50.
SITC 2020 - P48
Advances in Multiplexed Ion Beam Imaging (MIBI) for immune profiling of the tumor microenvironment
Segmentation and Classification of Single Cells using Multiplexed Ion Beam Imaging (MIBI)
Cancer Immunotherapy
Multiplexed Ion Beam Imaging (MIBI) For Characterization of the Tumor
Microenvironment Across Tumor Types
SITC 2018 - P106
Multiplexed Ion Beam Imaging For Characterization of the Tumor Microenvironment Across Tumor Types
A Structured Tumor Immune Microenvironment in Triple Negative Breast Cancer Revealed by Multiplexed Imaging
Pathology Visions 2018
Web Application for Management & Visualization of Highly Multiplexed Imaging Data


content of his pictures talks without doubt about North America and its most characteristic rituals of the new millennium.
out. It is a photography that transforms the most trivial things into unknown and unexpected ones.
what is photographed by Iñaki Bergera, may lack aesthetic value and therefore interest.
graffiti on a flaked wall.
interlude. Even though, as architecture, it is made out of craftwork and mechanical reproduction.


text:
Spud Thornhill: It's not always been kind to us but the FA Cup is still special to me
Spud Thornhill
Action from the last time Norwich City won an FA Cup tie - in the third round against Peterborough in 2013. Picture: Paul Chesterton/Focus Images
©Focus Images Limited www.focus-images.co.uk +447814 482222
The first weekend of the year means one thing, the third round of the FA Cup.
Another great time of the year for us football fans up and down the country. The oldest club competition in the world maybe slowly losing its magic, but I'm sure there are many fans like myself who will still have the buzz of the FA Cup and who may be thinking, maybe, just maybe, this is the year where we finally get some cup magic.
It may be a competition which has not given us Norwich fans much to shout about in the last 25 odd years, but I still have a lot of happy memories on why this great competition will always have a place in my heart.
I'm just old enough to remember when the FA Cup draw would be on a Monday lunchtime and the draw would be made live on the radio.
I remember hearing the fourth round draw in January 1987. Lunchtime at school, there were a few of us huddled round one of my teacher's radio and I still remembering hearing Wigan Athletic, versus Norwich City or Huddersfield Town.
Wigan who? I thought. Well we'll get past Huddersfield (Which we did) and easily get past Division Three Wigan.
The road to Wembley is ours this year I thought. Little did I know it would be the first time in my short time as a Canary where a team in a league lower than us would beat us. A goal from a certain Paul Jewell would do the damage.
At least we got revenge on Jewell in April 2011 when we beat his Ipswich 5-1!!
Wigan would be the first side to embarrass Norwich in the cup in my time as a City fan. Little did I know years later it would be a regular occurrence, with Sunderland, Brentford, Grimsby, West Ham, Bury, Leicester, Luton and Preston, all teams in a lower division than us at the time, knocking us out. Sunderland was probably the most painful.
Losing in the 1992 semi final against the Black Cats is one of my lowest and painful moments as a Canary. If I close my eyes, I can still see John Bryne heading the ball home in front of us at Hillsborough.
We may not have won an FA Cup tie since Peterborough in 2013, but at least we don't hold the current record for a league club without an FA Cup tie win. That's Ipswich Town. No surprises there. They haven't won since 2010. You know what to do Accrington Stanley!
I have happy memories from when I was a kid watching the FA Cup final at my grandparents. My brother, Martin, and I would from midday watch the whole build up of the final. We would constantly switch back and forwards between BBC and ITV as they provided coverage from breakfast at the hotel to the coach journey to Wembley.
Sadly after Norwich are knocked out and it just leaves the so-called bigger clubs, I lose interest in the FA Cup each year. With that, I don't think I have watched a whole cup final since 1998, when I was there at Wembley when Arsenal beat Newcastle.
Other memories are great away trips when Norwich have taken thousands away.
One of my first away days was at West Ham in the quarter finals. I still remember us taking 4,500 with plenty of inflatable canaries. But my all time favourite must be Paulton Rovers in November 2009. Not just because of the 7-0 win but the whole day. Going to the club and place similar to Wroxham was just great.
So on the 60th Anniversary this week when the famous Norwich team of 1959 beat Manchester United's Busby Babes 3-0, can the team of 2019 make our season even more special and produce an FA Cup run? Well, why not?
Daniel Farke has always respected our cup ties and I'm sure he'll be no different today, even if it does give some players a well deserved rest.
So come on you yellows, I'm greedy, not only do I want promotion, I want a cup run.
Que Sera Sera………
Spud's poser
Which former Norwich City player won a FA Cup winners medal with Portsmouth in 2008?
Answer: James Ashdown (Had a loan spell at Norwich in 2006 and made 2 appearance and was on the bench when Portsmouth won in 2008)
Daniel Farke


Falls are a big problem.
Falls in healthcare settings are a serious problem in Utah and around the country. Studies suggest that an estimated 2% to 10% of hospital inpatients fall during a hospital stay. According to the U.S. CDC, falls are the leading cause of death from unintentional injuries among U.S. adults 65 or older. The direct medical costs to treat individuals 65 and older injured in falls is estimated at over $19 billion dollars annually in the U.S.
The most common serious injury sustained from falls is a hip fracture. Of course, other serious injuries such as excessive bleeding, other fractures, and death also occur due to falls in hospitals, nursing homes, long-term care facilities, physical therapy offices, and other health care settings.
As a Utah medical malpractice attorney, I have successfully represented individuals in claims against health care providers, hospitals, and nursing homes for injuries sustained in falls.
I have found there are many things that can be done by hospitals and other health care professionals to reduce the risk of falls. Nursing homes, hospitals, and many other providers have a duty to develop and maintain fall prevention policies, procedures and tools. Patients should be assessed and reassessed for fall risk. Environmental inspections can be done to identify and eliminate risks for falls. In addition, staff should be educated about fall prevention and risk and how to respond and report falls.
Failure to take appropriate steps to prevent falls or to properly treat patients when they occur may be medical malpractice. Medical malpractice is a type of professional negligence where health care providers fail to follow the standards in their industry.
Of course not all falls in a hospital or doctor's office are the fault of the health care professional. However, if proper precautions are not taken, liability for falls may exist.
A mentally compromised elderly man fell from a window at a nursing home resulting in his death. The nursing home failed to properly supervise the individual and secure his environment.
A man suffered a hip fracture getting down from an examination table after a procedure. He was medicated and unstable, yet staff failed to assist him as required.
A woman was seriously injured during physical therapy. She was given an inappropriately difficult exercise on an improper machine, improperly monitored, and improperly assisted.
Each of these lawsuits resulted in significant settlements for the injured party. If you or a loved one have been injured in a fall at a Utah hospital, nursing home, or other medical facility, you need a Utah lawyer with experience in these types of claims. Please call attorney Jared Faerber at The Faerber Law Firm, PC for a free consultation.


text:
Another Louisiana Scenic River Saved From The Frackers
Sierra Club has been notified that Louisiana Department of Wildlife and Fisheries has denied a request from Comstock Resources to withdraw 12,600,000 gallons of water from the Amite River in East Feliciana Parish for use in fracking for oil and gas. The water would have been withdrawn from the Scenic River, used for fracking and then disposed as hazardous waste.
Update - LDWF will hold public hearing on Oct 29, 2014 to consider permit application to withdraw water from the Amite River for fracking
LDWF will hold public hearing on Oct 29, 2014 to consider Scenic River permit application #906 to withdraw water from the Amite River for hydraulic fracturing. The permit application is submitted by Comstock Resources to withdraw 12.6 million gallons from the Scenic Amite River.
We are asking Sierra Club members and allies who are opposed to fracking in the Florida parishes to show up at this public hearing. You can also submit written statements to the hearing record.
Four of the five permits to be considered at public hearing have been withdrawn
In a victory for the environment four out of the five applications to withdraw huge amounts of water from our scenic rivers have been withdrawn. This represents a significant victory for Sierra Club Delta Chapter. We have been in the forefront of the battle to protect our Louisiana Scenic Rivers by keeping the oil and gas companies from using huge quantities of scenic rivers water for fracking in the Florida parishes.
Sierra Club had filed comments on all the applications for withdrawal of water from scenic rivers pointing to numerous areas in which insufficient or contradictory information has been provided. And we demanded that public hearings be held regarding the permit applications. A public hearing had been set for Oct 29, 2014 for five recent applications to withdraw water. That public hearing is in now in doubt because four out of the five applications to be considered at that hearing have now been withdrawn. We have sent a request for clarification to LDWF and will update you here.
Recently withdrawn permits include #s 902, 903 and 911 on the Tickfaw River in St. Helena Parish, and #904 on the Amite River in East Feliciana Parish. The withdrawal of these permit applications means that we have saved a total of 75 million gallons of scenic river water from being turned into toxic waste.
Frackers Withdraw from the Tangipahoa River
The Delta Chapter Sierra Club has worked for years to protect Louisiana's Scenic Rivers. Our work has paid off on the Tangipahoa River. On 8-29-2014, Goodrich Petroleum voluntarily withdrew its Application for a Scenic River Permit to "extract" twenty five million (25,000,000) gallons of "outstanding natural resource" water from the tiny river for use as fracking fluid.
Fracking Threatens Scenic Rivers in the Florida Parishes
Oil and gas development companies are proposing to drill wells and conduct fracking operations in the Tuscalusa Shale in East Feliciana, St. Helena, Tangipahoa and St. Tammany Parishes in eastern Louisiana. One of the major impacts of the proposed fracking for natural gas and oil will be the huge volumes of water required. Each fracking operation can have three, five or up to ten or twelve wells and can use anywhere from 3 to 8 million gallons of fresh water. The water for each well may be mixed with 60 to 160 tons of chemicals used to facilitate the fracking process.
Wilma Subra's Fracking Presentation at the Castine Center May 12, 2014
This is a highly informative presentation about the potential effects of fracking in St. Tammany Parish. The presentation was given by Dr. Wilma Subra representing LEAN at the Castine Center in Mandeville Louisiana on May 12, 2014.