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Met Office Hadley Centre - Observations and Climate
The Met Office Hadley Centre is one of the UK's foremost climate change research centres.
The Hadley Centre produces world-class guidance on the science of climate change and provide a focus in the UK for the scientific issues associated with climate science.
Largely co-funded by Department of Energy and Climate Change (DECC) and Defra (the Department for Environment, Food and Rural Affairs), the centre provides in-depth information to, and advise, the Government on climate science issues.
As one of the world's leading centres for climate science research, the Hadley Centre scientists make significant contributions to peer-reviewed literature and to a variety of climate science reports, including the Assessment Report of the IPCC. The Hadley Centre climate projections were the basis for the Stern Review on the Economics of Climate Change.
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Toasting the ladies on National Toast Day that put so much time and effort into several successful book launch signings.
Thank you Ritz Carlton, Georgetown! Magnificent!
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An essay by Taylor Smith on Anthony Watts' Watts Up With That? blog caught my attention: "EPA 'Public Listening Session' Turns Into Sierra Club Talking Session."
An excerpt:
Although the EPA hearing yielded the same mix of speakers, this time I noticed they were all wearing green Sierra Club "Climate Action Now" shirts.
The reason for this, I would later learn, was that the Sierra Club had mobilized hundreds of activists, transported them via bus (I presume of the fossil-fuel powered kind), prepped their testimonies the night before, and completely dominated the morning speaker slots. (There were several coal industry representatives in the morning, and a few other dissenters, including Heartland Policy Adviser Paul Driessen, who covered his experience here). By the afternoon, the Sierra Club had completely monopolized the speaking time (at least in the room I was in).
After the hearing, everyone was invited to a "Climate Social" held at the Sierra Club's office with Sen. Dick Durbin (D-IL), Lt. Gov. Sheila Simon, and Illinois state Sen. Michael Frerichs.
Now maybe it's just me, but I felt a slight level of discomfort when I saw a single organization dominate a "public" hearing in the way that they did. I don't care what the organization is or what they say they stand for, because if their 2011 listed revenue is over $97 million, then you know not all of it could have fallen in their laps from heaven.
The session concerned EPA carbon regulations, but I have attended forestry-oriented public meetings and listening sessions at which most, if not all, attendees seemed to represent the same position, if not the same organization. I've been to others at which everyone seemed independent. In this case, the Sierra Club didn't do anything wrong; I'll bet that industry groups have done the same at hearings on various issues. It's a bit like asking its members to sign a form letter and e-mail it to an agency. But I'm curious about the effect of "packing" public meetings like this. Agencies these days often count and report the number of "original" letters and form letters for project or plan proposals. Do agencies somehow give more or less weight to public comments from attendees organized or transported by a single group?
Note that Driessen was one of the speakers and he certainly wasn't wearing a Sierra Club shirt. So, Smith was incorrect — they were not "all wearing green Sierra Club "Climate Action Now" shirts." The photo on the blog shows a lot of those green shirts in the audience.


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Division of Wildlife Conservation (DWC) Publication Details
An animal movement model incorporating home range and habitat selection
- Reference: Christ, A., J. Ver Hoef, and D. L. Zimmerman. 2008. An animal movement model incorporating home range and habitat selection. Environmental and Ecological Statistics 15(1):27-38. http://doi.org/10.1007/s10651-007-0036-x
- Audiences: General Public, Scientist, Wildlife Manager
- Authors: Aaron M. Christ, Jay M. Ver Hoef, Dale L. Zimmerman
- Funding Sources:
- Grants:
- GMUs or Areas: 01, 02, 03, 04
- Keywords: brown bear, Ursus arctos, GPS telemetry, Markov chain Monte Carlo, resource selection function, utilization distribution, vector autoregression
- Link: http://doi.org/10.1007/s10651-007-0036-x (Offsite)
- Partners: Federal Aid-Wildlife Restoration Program
- Primary Authors: Aaron M. Christ
- Programs: Wildlife Research
- Project Numbers:
- Publication Types: Journal Article/External Publication
- Regions: Region I - Southeast Alaska, Statewide
- Species: Brown Bear
- Species Categories: Big Game, Mammals
- Title: An animal movement model incorporating home range and habitat selection
- Topics: Habitat, Distribution and Movements (including Migration), Research, Behavioral Ecology
- Year: 2008
See more: Wildlife Publications


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www.leanblog.org - Mark Graban has been faithfully maintaining this blog since 2005. The earlier posts are more lean manufacturing focused, and the later posts are more lean hospital focused. This blog is updated daily and has lots of good info.
theleanedge.org - This is a site that looks like a blog at first glance, but is really a discussion between some of the top lean leaders. Lots of great discussion and learning can be found on this site.
www.lean.org/shook - These are John Shook's newsletters. John is now the CEO of LEI (Lean Enterprise Institute) and has a lot of lean experience.
www.lean.org/balle - This is a column written by Michael Balle that has great lean insights. As a side note, Micheal and Freddy Balle have written my favorite fiction style lean business books.
www.gembapantarei.com - Jon Miller's blog. This blog has great info, but isn't updated as regularly as leanblog and others.
www.shingoprize.org - The Shingo Institute has excellent training and an excellent lean model (the Shingo Model). The most eye opening lean training that I have attended was by The Shingo Institute.
www.gembaacademy.com - Gemba Academy has great lean and six sigma training at a reasonable price.
www.lean.org - Lean.org is LEI's website and has lots of great information from newsletters to webinars and simulations. Dig around a bit and you will be pleased what you can find.
Lean Tempo Basic is a plug and play productivity tracker for only $450.
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Manual Medium Incision Cataract Surgery with Descemet's Stripping Endothelial Keratoplasty: A Novel Triple Procedure
Purpose. To describe the surgical technique and outcomes of combined Descemet's stripping endothelial keratoplasty and medium incision manual cataract surgery (MICS) in Chinese eyes. Methods. Surgery was performed in 8 eyes of 7 patients (5 females, 2 males). Primary outcomes included success of the surgery and final outcomes. Results. Surgery was performed in patients with Fuchs' endothelial dystrophy and cataract (mean age years). MICS tunnel was used to insert the donor lenticule into the anterior chamber. All surgeries were performed successfully. Graft dislocation was seen in 1 eye requiring repositioning with intracameral sulfur hexafluoride gas on the first postoperative day. Graft rejection was noted in one patient at the end of one year. The mean decimal best-corrected visual acuity improved from to . Suboptimal visual acuity in 2 cases was due to radiotherapy-related optic neuropathy and myopic maculopathy . The mean target spherical refraction was diopters (myopic) and the mean achieved spherical refraction was 1.18 ± 0.87 diopters (hyperopic) resulting in a mean hyperopic shift of 2.2 diopters. Conclusions. The approach of combined Descemet's stripping endothelial keratoplasty and MICS is a viable surgical technique for cases with endothelial dysfunction and cataract.
1. Introduction
Lamellar corneal transplantation surgery allows for selective replacement of the diseased corneal endothelium [1–4]. Descemet's stripping endothelial keratoplasty (DSEK) and Descemet's membrane endothelial keratoplasty (DMEK) have been shown to have superior outcomes compared to penetrating keratoplasty in terms of postoperative astigmatism and visual function [5, 6]. Fuchs' endothelial dystrophy is one of the main indications for endothelial keratoplasty. However, patients with Fuchs' endothelial dystrophy frequently suffer from coexisting cataract. Cataract surgery has been successfully combined with penetrating keratoplasty since the 1970s and became popular as the "triple procedure." More recently, the combination of endothelial keratoplasty with cataract surgery was named the "new triple procedure" [7]. Advantages of the triple procedure include faster visual rehabilitation and no further endothelial damage induced by sequential cataract surgery. In the classic triple procedure, penetrating keratoplasty induces changes in the anterior and posterior corneal curvature with reduced predictability because of an alteration in the keratometric readings needed for intraocular lens power calculation. This leads to the increased likelihood of postoperative refractive errors and anisometropia. DSEK on the other hand induces no significant changes in corneal topography and therefore the refractive outcomes after triple DSEK are more predictable, although a mild postoperative hyperopic shift may be observed [8].
In the present study, we describe a novel surgical approach of combined Descemet's stripping endothelial keratoplasty and medium incision cataract surgery (MICS).
2. Materials and Methods
2.1. Surgical Technique
All surgeries were performed under retrobulbar anesthesia using a 1 : 1 mixture of 2% lignocaine and 0.5% bupivacaine. A temporal approach was used. Conjunctival limbal peritomy was started with two 3 mm oblique relaxation cuts at the 7- and 11-o'clock positions (for the right eye). This was followed by a 10 to 12 mm limbal peritomy (Figure 1(a)). An 8 mm long, straight, partial thickness scleral incision with its center 2 mm from the limbus was made with a 2.5 mm crescent knife (Alcon Surgicals, Fort Worth, TX, USA). Using the crescent knife, a 4 mm long sclerocorneal tunnel was dissected from the scleral incision, extending approximately 2 mm into clear cornea (Figure 1(b)). Three paracentesis sites were created with a 15° slit knife at the 3-, 6-, and 12-o'clock positions (for the right eye). 0.1 mL of trypan blue (0.6 mg/mL) (VisionBlue; Dutch Ophthalmic Research Center, Amsterdam, Netherlands) was used to stain the anterior capsule under air. A dispersive viscoelastic agent (Viscoat, Alcon Laboratories Inc.) was used to reform the anterior chamber. The anterior corneal surface was marked using an 8 mm marker. A 3 mm keratome (Alcon Surgicals, Fort Worth, TX, USA) was introduced into the center of the tunnel, and the anterior chamber was entered. Anterior capsulorhexis was performed using a pair of capsulorhexis forceps or a bent 27-gauge needle (Figure 1(c)). A gentle hydrodissection was performed to loosen the attachments of the nucleus to the capsular bag. Two Sinskey hooks were used to dislocate the nucleus from the bag as described previously [9].
The internal entry across the entire length of the sclerocorneal tunnel was completed with a keratome. An anterior chamber maintainer was then inserted into the distal paracentesis wound. Nucleus delivery was completed with a vectus (Figure 1(d)). Subsequently, irrigation and aspiration were performed using a 23-gauge aspiration cannula (Duckworth & Kent Ltd., Baldock, Hertfordshire, England). The anterior chamber was filled with a cohesive viscoelastic agent (ProVisc, Alcon Laboratories Inc.). An intraocular lens was inserted in the capsular bag. With the AC maintainer infusion on, the residual viscoelastic agent was removed using the aspiration cannula. Descemet's membrane was stripped with a reverse Sinskey hook utilizing the epithelial mark as a guide (Figure 1(e)). Descemet's membrane was removed in total.
Donor lenticules were prepared either manually in DSEK or by microkeratome in Descemet's stripping automated endothelial keratoplasty (DSAEK). In DSEK, the donor's cornea was mounted in a pressurized artificial anterior chamber filled with Optisol. Manual dissection was initiated in the periphery with a diamond knife, which was calibrated to a desired depth. The corneal stromal dissection was completed with a crescent knife. The donor lenticule was then placed endothelial side up and trephination was performed from the endothelial side. The anterior stromal cap was carefully separated from the underlying donor lenticule. For DSAEK, precut eye bank-prepared tissue was available from the local eye bank.
A 5 mm Sheet glide was inserted into the anterior chamber through the scleral wound (Figure 1(f)). Viscoelastic agent (Healon, Advanced Medical Optics, Santa Ana, CA) was placed on the surface of the glide. The donor lenticule was transferred endothelial side down onto the viscoelastic-coated Sheet glide (Figure 1(g)). In seven out of the eight cases, a pair of Tan's forceps (Asico, Westmont, USA) was utilized to draw the donor lenticule into the anterior chamber through the nasal paracentesis (Figure 1(h)). During this maneuver, anterior chamber was maintained via the infusion line. The infusion line was removed after the graft was pulled into the anterior chamber. In one case, the donor lenticule was inserted after being taco-folded and was then unfolded inside the anterior chamber with the injection of filtered air. At the end of the surgery, the anterior chamber was filled with air for 8–10 minutes (Figure 1(i)). Approximately 50% of the air was left in the anterior chamber. The side ports were hydrated, and the main wound was sutured with interrupted 10-0 nylon sutures when needed.
3. Results and Discussion
Combined EK and MICS surgery was performed in 8 eyes of 7 patients (5 females, 2 males) with Fuchs' endothelial dystrophy and cataract. The mean age of the patients was years (Table 1). Endothelial graft was prepared manually in 4 eyes and with microkeratome in 4 eyes. Surgery was performed successfully in all eyes. There were no intraoperative complications. Graft dislocation was seen in 1 eye requiring repositioning with intracameral sulfur hexafluoride (18%) gas on the first postoperative day. One case had mild inferior graft displacement that did not require any surgical intervention. Graft rejection was noted in one patient at the end of one year. Quick resolution of graft rejection was achieved with intensive corticosteroids.
The mean decimal best-corrected visual acuity (Snellen) improved from to . Six out of 8 cases (75%) achieved a best-corrected visual acuity of ≥0.3 at the end of 1 year. Suboptimal visual acuity in 2 cases was due to radiotherapy-related optic neuropathy () and myopic maculopathy (). Two cases had developed posterior capsular opacification postoperatively.
Sanders—Retzlaff—Kraff/Theoretical (SRK/T) formula was employed for the calculation of intraocular lens power before the surgery. The mean target spherical refraction was diopters (myopic) and the mean achieved spherical refraction was diopters (hyperopic) resulting in a mean hyperopic shift of 2.2 diopters.
Selective corneal transplantation has slowly replaced the conventional "one for all" full-thickness keratoplasty [10]. Consequently, the definition of a triple procedure has been expanded to include EK with cataract surgery. However, it may not be feasible to perform phacoemulsification in all cases undergoing a triple procedure due to the lack of resources (especially in developing economies) or expertise (very dense mature cataracts) or both. Both phacoemulsification and small-incision cataract surgery have been shown to be safe and effective for visual rehabilitation of cataract patients [11]. One prospective, comparative study found that although the effectiveness of MICS and phacoemulsification was not significantly different, phacoemulsification was associated with higher costs [12]. Similar observations were made in other studies [13]. It is often difficult to perform phacoemulsification in cases with severe corneal edema, which impairs adequate intraoperative visualization. Our novel approach of combined EK and MICS provides an effective solution to these issues, since the approach and surgical steps are inherently complementary to each other. The MICS technique used in our study has been described earlier [9]. The highlight of this surgical technique includes the use of a large scleral tunnel fashioned temporally in order to provide easy access during the surgery. This is pertinent in Chinese eyes with small palpebral fissures and shallow anterior chamber depth [3]. In our study, cataract surgery was performed through a sutureless scleral tunnel. After cataract extraction and intraocular lens implantation, we used the same scleral tunnel to insert the donor lenticule. The use of a large scleral tunnel and an anterior chamber glide does not require folding of the graft thereby minimizing the risk of endothelial trauma. Successful use of scleral tunnel during EK has been described previously using Busin's glide [14]. However, we feel that it is challenging to introduce Busin's glide into the anterior chamber in Chinese eyes that are characteristically small and have a shallow anterior chamber. Hence, we have adopted the use of pull-through technique and anterior chamber Sheet glide for graft insertion at our center. In the present study, all surgeries were performed successfully using the same surgical technique without any intraoperative problems. A good visual outcome was achieved in majority of the cases.
One case (12.5%) suffered donor dislocation in our case series. This may be related to retained viscoelastic agent in the donor-host interface. Although we tried to minimize the use of viscoelastic agent during the donor insertion, it is not possible to entirely eliminate the use of viscoelastic agents during EK using a Sheet glide. Nevertheless, intracameral sulfur hexafluoride was used to successfully reattach the donor lenticule. Graft dislocations after EK triple procedure have been reported to occur in 1.77% of the cases by Terry et al. [15] and up to 14.3% of the cases by Covert and Koenig [7]. Suh et al. reported the results of EK in 118 eyes of which a combination of phacoemulsification and EK was performed in 41 eyes [16]. Overall, graft detachment was the most commonly observed complication (23% of eyes) in their study [16]. However, the authors did not specify the proportion of graft dislocations after triple procedure. Although it is believed that the risk of graft dislocations is low with the use of anterior chamber maintainer thereby avoiding viscoelastic during EK surgery [14], a large, randomized, prospective study of EK surgery with or without the use of viscoelastic agent can verify the relative rates of tissue dislocation resulting from this single factor [15].
In our study, BCVA of 0.3 or better was achieved in 6 out of 8 cases. Visual outcomes were suboptimal in 2 cases due to associated problems in the posterior segment. Terry et al. reported a best spectacle corrected visual acuity of 0.5 or higher in 97% of the patients at the end of 12 months [15], while another study reported excellent visual outcomes (average 20/34) after EK triple procedure [7]. The visual outcomes after triple procedure have generally been reported to be good. One of the unresolved issues is the preoperative detection of posterior segment problems especially cystoid macular edema that might affect the visual acuity outcomes in these patients. Similar to conventional triple procedure, careful preoperative retinal screening (if the corneal clarity permits an adequate view of the posterior segment) should be performed.
In the present study, the mean target preoperative spherical refraction was 1.1 diopters (myopic). However, a mean hyperopic shift of more than 2 diopters was observed postoperatively. Because early experience with EK had demonstrated a trend towards postoperative hyperopic shift in refraction of approximately 1 diopter, eyes undergoing a triple procedure in our series were actually targeted between −0.89 and −1.34 diopters preoperatively. However, only two out of eight eyes included in this study achieved plano refraction. Our findings match the earlier report by Covert and Koenig [7] who reported a mean hyperopic shift of 1.13 diopters in their cases. Terry et al. however did not observe any significant hyperopic shift in their cases that underwent triple procedure [15]. The hyperopic shift observed in our study may be attributed to the learning curve in terms of intraocular lens power selection during EK triple procedure at our centre. The graft thickness would be variable in our cases that underwent DSEK with manual preparation of the donor lenticule. Another possibility is inaccurate preoperative keratometry values in these cases due to irregular corneal surface.
4. Conclusions
Overall, our novel approach of combined EK and MICS can be performed for patients with Fuchs' corneal dystrophy and dense cataract. The limitations of the current study include a small sample size and retrospective design. We did not have preoperative data for all our patients. Further studies with large sample size, a comparative group, and long-term outcomes are desirable.
Conflict of Interests
The authors declare that there is no conflict of interests regarding the publication of this paper.
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The Eagles put forth one of their best defensive efforts of the season and got two TDs from LeSean McCoy as they downed the Dolphins 26-10 at Sun Life Stadium. The win moves the Eagles to 5-8 and keeps their small playoff hopes alive.
The Eagles defense was everything they weren't on the Thursday night game in Seattle. In that game, Marshawn Lynch was running all over them and the defense could do nothing to stop him nor could they force a turnover. This afternoon against Miami, the Eagles were rock solid in short yardage and forced three Miami turnovers leading to 17 Eagles points. To top it all off, they also scored 2 points with a safety.
How good were the Eagles in short yardage? They stuffed Miami on two 3rd & 1s, two 4th & 1s, a 3rd and 3, a 2nd & goal from the 2 & a 3rd and goal from the 2. The D also registered a season high nine sacks, their highest total since a 2008 game against the Steelers. The defense was so stifling today that after the Brandon Marshall TD catch in the first quarter, nearly 35 minutes of game time would go by before the Dolphins would score again.
On offense, LeSean McCoy keeps rushing toward history with two more scores today. He now needs just one more rushing TD this season to equal Steve Van Buren's franchise record of 14, which has stood since 1945. Also. one more receiving or rushing TD would tie McCoy with Van Buren for the most total TDs in a season. With three and a half games left, it seems as though McCoy is very likely to own both franchise records before the end of the season.
McCoy's two TDs today are even more impressive coming against the Dolphins, who have one of the best run defenses in football. Prior to this game, they had allowed just three rushing TDs all season. McCoy is also the first RB with two rushing TDs in a game against Dolphins since Fred Jackson in 2009. Of course, this is not to say it was a great day for McCoy overall, who aside from the two TDs, had a very frustrating afternoon. The Eagles offensive line was completely dominated in both the pass and the run. McCoy had defenders in the backfield on most plays and could only manage 38 yards on 27 carries. The line wasn't much better against the pass as Michael Vick was sacked four times and forced to make at least two or three of those patented impossible Vick escapes.
Overall it was a comfortable win by the Eagles and one that at least keeps them in the playoff hunt for what that's worth. The Eagles still need to win out to have any shot. The Giants beating the Cowboys tonight would also help.


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"Every moment is a fresh beginning."
Paula Boggs Band blends jazz and Americana, releasing a steady stream of music since 2010. Six years ago they released 3rd album Elixir, The Soulgrass Sessions, produced by Grammy© winning Trina Shoemaker, and after Elixir, multi-instrumentalists Paul Moore and Darren Loucas, bassist Alex Dyring and drummer Jacob Evans joined original members Boggs, on vocals, guitar and ukulele, percussionist Tor Dietrichson and banjo player Mark Chinen.
Moore, Dyring and Evans are conservatory trained. Dyring and Evans are second generation professional musicians. "Mistletoe & Shiny Guitars," the band's first holiday song came in 2018. EP "Electrokitty Sessions" and single "America 2020," produced by multi-Grammy© nominated Tucker Martine followed in 2020.
Paula Boggs Band is sponsored by Deering Banjos, Breedlove Guitars and Radial Engineering. Their 4th studio album, "Janus," also produced/engineered by Martine and featuring Carolina Chocolate Drops co-founder Dom Flemons, released in 2022. Their next releases are "Traces of You Instrumental" single and music video Fall 2023. Stay tuned.
"This Seattle combo dubs its sound "soulgrass," since it combines bluegrass and Americana idioms. This track is a story song telling of Paula's enslaved ancestor in Alabama and his journey through the postbellum Jim Crow South. Flemons, a veteran of the Carolina Chocolate Drops, shares lead vocals. " - MusicRow magazine
"The harrowing, chanted chorus [of Ponies] is immediately followed by verse after verse from Boggs, as she weaves soul, bluegrass, country, and even a little bit of jazz into a beautiful yarn about finding the romantic side of life in any given circumstance." - Billboard
"Rewriting the bluegrass story from a black perspective." - AmericanaUK
"["Ponies is a]n ambitious charmer that curates with Dylan "Desire" era multi-dimensional expressiveness along with storied lyrics worth continually revisiting." - Glide Magazine
"Boggs is like the Dylan, the Peter, Paul, and Mary, the Joan Baez of this era."
Phil King, AudioFuzz.com
"Paula Boggs Band sets themselves apart distinctly by Boggs' stunning vocals…this Seattle band sounds the part of a bygone era and part refreshingly modern, an exciting contributor to the Pacific Northwest's diverse music scene." Glide Magazine
Paula Boggs:
Mark Chinen:
Alex Dyring:
Tor Dietrichson:
Paul Matthew Moore:
Jacob Evans: drums
Darren Loucas:
mandolin, guitar, harmonica, fiddle, lap steel, vocals
"Paula Boggs Band joins with Dom Flemons to share "King Brewster," a song from Janus written about Boggs' enslaved-then-emancipated ancestor." - Americana Music Association
"The record [album Janus] includes deeply personal themes of ancestry, memory, and love. The storytelling on this record will pull you in, but it's the musicianship that ultimately takes center stage, thanks to an elegant, groove-laden soundscape crafted by an all-star backing band." - No Depression
"Boggs captures a raw nostalgia ...that might catch you by surprise. She has created a gentle groove for your heartache." - Americana Highways
"This veteran Americana act boasts a range of influences from classic — James McMurtry and Bruce Springsteen — to more contemporary — the Drive-By Truckers. The group describes itself as "soulgrass." An unfamiliar tag, sure, but not to be dismissed lightly in this age of microgenres." Current San Antonio
"Mark Chinen played...banjo. I have not heard anyone play a banjo quite like that before...he made it sound like a big city brother to the banjo...when this talented man moves his finger down the strings of a banjo it is magic!" Juanita Smith - From the Cradle to the Stave, Mobile AL
"Boggs makes...urban, jazzy music...within the structures of...folk, bluegrass, and...blues...[s]he calls... "soulgrass," and reminds me a little of Gil Scott-Heron, if only for the razor-intensity of her words...in a croony-rich street voice...evocative and easy to like." Dave Good, San Diego Reader


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text:
|Trade names
|Lariam, Mephaquin, Mefliam, others
|Clinical data
|Main uses
|Prevent or treat malaria[1]
|Side effects
|Vomiting, diarrhea, headaches, sleep disorders, rash[1]
|Routes of
|By mouth (tablets)
|Defined daily dose
|1 g [2]
|External links
|Legal status
|Extensive liver; main metabolite is inactive
|Elimination half-life
|2 to 4 weeks
|Primarily bile and feces; urine (9% as unchanged drug, 4% as primary metabolite)
|Chemical and physical data
|Molar mass
|378.318 g·mol−1
|3D model (JSmol)
|Racemic mixture
Mefloquine, sold under the brand names Lariam among others, is a medication used to prevent or treat malaria.[1] When used for prevention it is typically started before potential exposure and continued for several weeks after potential exposure.[1] It can be used to treat mild or moderate malaria but is not recommended for severe malaria.[1] It is taken by mouth.[1]
Common side effects include vomiting, diarrhea, headaches, sleep disorders, and a rash.[1] Serious side effects include potentially long-term mental health problems such as depression, hallucinations, and anxiety and neurological side effects such as poor balance, seizures, and ringing in the ears.[1] It is therefore not recommended in people with a history of mental health problems or epilepsy.[1] It appears to be safe during pregnancy and breastfeeding.[3]
Mefloquine was developed by the United States Army in the 1970s and came into use in the mid 1980s.[4][5][6] It is on the World Health Organization's List of Essential Medicines.[7] It is available as a generic medication.[1] The wholesale price in the developing world is about US$0.6–1.3 per dose.[8] In the United Kingdom it costs the NHS £1.82 per dose.[9] In the United States it costs about $10 a dose.[1]
Medical uses
Mefloquine is used to both prevent and treat certain forms of malaria.[10]
Malaria prevention
Mefloquine is useful for the prevention of malaria in all areas except for those where parasites may have resistance to multiple medications,[11] and is one of several anti-malarial medications recommended by the United States Centers for Disease Control and Prevention for this purpose. It is also recommended by the Infectious Disease Society of America for malaria prophylaxis as a first or second-line agent, depending on resistance patterns in the malaria found in the geographic region visited.[12][13] It is typically taken for one to two weeks before entering an area with malaria.[10] Doxycycline and atovaquone/proguanil provide protection within one to two days and may be better tolerated.[14][15] If a person becomes ill with malaria despite prophylaxis with mefloquine, the use of halofantrine and quinine for treatment may be ineffective.[16]: 4
Malaria treatment
Mefloquine is used as a treatment for chloroquine-sensitive or resistant Plasmodium falciparum malaria, and is deemed a reasonable alternative for uncomplicated chloroquine-resistant Plasmodium vivax malaria.[10][16] It is one of several drugs recommended by the United States' Centers for Disease Control and Prevention.[17] It is not recommended for severe malaria infections, particularly infections from P. falciparum, which should be treated with intravenous antimalarials.[10][16] Mefloquine does not eliminate parasites in the liver phase of the disease, and people with P. vivax malaria should be treated with a second drug that is effective for the liver phase, such as primaquine.[16]: 4
Resistance to mefloquine is common around the west border in Cambodia and other parts of Southeast Asia.[18] The mechanism of resistance is by increase in Pfmdr1 copy number.[19]
The defined daily dose is 1 gram (by mouth).[2] In adults the dose for prevention is 250 mg once per week.[1] This should be started 1 to 2 weeks before potential exposure and continued for 4 weeks after potential exposure.[1] For the treatment of malaria 750 mg followed by 500 mg after 6 to 12 hours may be used, but is generally only recommended if other options are not avaliable.[20]
Side effects
Common side effects include vomiting, diarrhea, headaches, and a rash.[1] Severe side effects requiring hospitalization are rare,[11] but include mental health problems such as depression, hallucinations, anxiety and neurological side effects such as poor balance, seizures, and ringing in the ears.[1] Mefloquine is therefore not recommended in people with a history of psychiatric disorders or epilepsy.[1]
Neurologic and psychiatric
In 2013 the United States Food and Drug Administration added a boxed warning to the U.S. label of mefloquine regarding the potential for neuropsychiatric side effects that may persist even after discontinuing administration of the drug.[21][22] In 2013 the FDA stated "Neurologic side effects can occur at any time during drug use, and can last for months to years after the drug is stopped or can be permanent."[23] Neurologic effects include dizziness, loss of balance, seizures, and tinnitus. Psychiatric effects include nightmares, visual hallucinations, auditory hallucinations, anxiety, depression, unusual behavior, and suicidal ideations.
Central nervous system events requiring hospitalization occur in about one in 10,000 people taking mefloquine for malaria prevention, with milder events (e.g., dizziness, headache, insomnia, and vivid dreams) in up to 25%.[24] When some measure of subjective severity is applied to the rating of adverse events, about 11-17% of travelers are incapacitated to some degree.[14]
Mefloquine may cause abnormalities with heart rhythms that are visible on electrocardiograms. Combining mefloquine with other drugs that cause similar effects, such as quinine or quinidine, can increase these effects. Combining mefloquine with halofantrine can cause significant increases in QTc intervals.[16]: 10
Mefloquine is contraindicated in those with a previous history of seizures or a recent history of psychiatric disorders.[10]
Pregnancy and breastfeeding
Available data suggests that mefloquine is safe and effective for use by pregnant women during all trimesters of pregnancy,[25] and it is widely used for this indication.[26] In pregnant women, mefloquine appears to pose minimal risk to the fetus,[26][27] and is not associated with increased risk of birth defects or miscarriages.[28] Compared to other malaria chemoprophylaxis regimens, however, mefloqinone may produce more side effects in non-pregnant travelers.
Mefloquine is also safe and effective for use during breastfeeding,[25] though it appears in breast milk in low concentrations.[11][16]: 9 The World Health Organization (WHO) gives approval for the use of mefloquine in the second and third trimesters of pregnancy and use in the first trimester does not mandate termination of pregnancy.[11]
Mefloquine is metabolized primarily through the liver. Its elimination in persons with impaired liver function may be prolonged, resulting in higher plasma levels and an increased risk of adverse reactions. The mean elimination plasma half-life of mefloquine is between two and four weeks. Total clearance is through the liver, and the primary means of excretion is through the bile and feces, as opposed to only 4% to 9% excreted through the urine. During long-term use, the plasma half-life remains unchanged.[29][30]
Liver function tests should be performed during long-term administration of mefloquine.[31] Alcohol use should be avoided during treatment with mefloquine.[32]
Specifically it is used as mefloquine hydrochloride.
Mefloquine is a chiral molecule with two asymmetric carbon centres, which means it has four different stereoisomers. The drug is currently manufactured and sold as a racemate of the (R,S)- and (S,R)-enantiomers by Hoffman-LaRoche, a Swiss pharmaceutical company. Essentially, it is two drugs in one. Plasma concentrations of the (–)-enantiomer are significantly higher than those for the (+)-enantiomer, and the pharmacokinetics between the two enantiomers are significantly different. The (+)-enantiomer has a shorter half-life than the (–)-enantiomer.[14]
Mefloquine was formulated at Walter Reed Army Institute of Research (WRAIR) in the 1970s shortly after the end of the Vietnam war. Mefloquine was number 142,490 of a total of 250,000 antimalarial compounds screened during the study.[4]
Mefloquine was the first Public-Private Venture (PPV) between the US Department of Defense and a pharmaceutical company. WRAIR transferred all its phase I and phase II clinical trial data to Hoffman-LaRoche and Smith Kline. FDA approval as a treatment for malaria was swift. Most notably, phase III safety and tolerability trials were skipped.[4]
The drug was first approved in Switzerland in 1984 by Hoffmann-LaRoche,[33] who brought it to market with the name Lariam.[34]
However, mefloquine was not approved by the FDA for prophylactic use until 1989. This approval was based primarily on compliance, while safety and tolerability were overlooked.[4] Because of the drug's very long half-life, the Centers for Disease Control originally recommended a mefloquine dosage of 250 mg every two weeks; however, this caused an unacceptably high malaria rate in the Peace Corps volunteers who participated in the approval study, so the drug regimen was switched to once a week.[14]
By 1991, Hoffman was marketing the drug on a worldwide basis.[34]
By the 1992 UNITAF, Canadian soldiers were being prescribed the drug en masse.[35]
By 1994, medical professionals were noting "severe psychiatric side effects observed during prophylaxis and treatment with mefloquine", and recommending that "the absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed."[36] Other doctors at the University Hospital of Zurich noted in a case of "a 47-year-old, previously healthy Japanese tourist" who had severe neuropsychiatric side-effects from the drug that[37]
The neuropsychiatric side effects of the antimalarial drug mefloquine are well documented. They include anxiety, depression, hallucinations, acute psychosis, and seizures. The incidence of these side effects is 1 in 13,000 with prophylactic use and 1 in 250 with therapeutic use.
The first randomized, controlled trial on a mixed population was performed in 2001. Prophylaxis with mefloquine was compared to prophylaxis with atovaquone-proguanil. Roughly 67% of participants in the mefloquine arm reported greater than or equal to one adverse event, vs 71% in the atovaquone-proguanil arm. In the mefloquine arm, 5% of the users reported severe events requiring medical attention, vs 1.2% in the atovaquone-proguanil arm.[4][38]
In August 2009, Roche stopped marketing Lariam in the United States.[39]
Retired soldier Johnny Mercer, who was later appointed Minister for Veterans Affairs by Boris Johnson, told in 2015 that he had received "a letter about once or twice a week" about ill-effects from the drug.[40] In July 2016, Roche took this brand off the market in Ireland.[39]
In 2006, the Australian military deemed mefloquine "a third-line drug" alternative, and over the five years from 2011 only 25 soldiers had been prescribed the drug, and only in cases of their intolerance for other alternatives.[39] Between 2001 and 2012, 16000 Canadian soldiers sent to Afghanistan were given the drug as a preventative measure.[39] In 2013, the US Army banned mefloquine from use by its special forces such as the Green Berets.[39] In autumn 2016, the UK military followed suit with their Australian peers after a parliamentary inquiry into the matter revealed that it can cause permanent side effects and brain damage.[39]
In early December 2016, the German defence ministry removed mefloquine from the list of medications it would provide to its soldiers.[39]
In autumn 2016, Canadian Surgeon General Brigadier General Hugh Colin MacKay told a parliamentary committee that faulty science supported the assertion that the drug has indelible noxious side effects. An expert from Health Canada named Barbara Raymond told the same committee that the evidence she had read failed to support the conclusion of indelible side effects.[39] Canadian soldiers who took mefloquine when deployed overseas have claimed they have been left with ongoing mental health problems.[41]
In June 2010, the first case report appeared of a progressive multifocal leukoencephalopathy being successfully treated with mefloquine. Mefloquine can also act against the JC virus. Administration of mefloquine seemed to eliminate the virus from the patient's body and prevented further neurological deterioration.[42]
WRAIR has published several papers outlining ongoing efforts at that institution to make mefloquine safer by producing a drug composed of only the (+)-enantiomer.
Mefloquine alters cholinergic synaptic transmission through both postsynaptic [43] and presynaptic actions.[44] The postsynaptic action to inhibit acetylcholinesterase changes transmission across synapses in the brain.[45]
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 "Mefloquine Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 2015-12-08. Retrieved 27 Nov 2015.
- ↑ 2.0 2.1 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 3 August 2020. Retrieved 22 September 2020.
- ↑ "Mefloquine (Lariam) Use During Pregnancy". Drugs.com. Archived from the original on 31 March 2019. Retrieved 31 March 2019.
- ↑ 4.0 4.1 4.2 4.3 4.4 Croft, AM (2007). "A lesson learnt: the rise and fall of Lariam and Halfan". J R Soc Med. 100 (4): 170–4. doi:10.1258/jrsm.100.4.170. PMC 1847738. PMID 17404338.
- ↑ Ravina, Enrique (2011). The evolution of drug discovery : from traditional medicines to modern drugs (1. Aufl. ed.). Weinheim: Wiley-VCH. p. 136. ISBN 9783527326693.
- ↑ Jeremy Farrar; Peter J. Hotez; Thomas Junghanss (2013). Manson's tropical diseases (23rd ed.). Oxford: Elsevier/Saunders. p. 569. ISBN 9780702053061.
- ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ↑ "Mefloquine". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 27 November 2015.
- ↑ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 607. ISBN 9780857113382.
- ↑ 10.0 10.1 10.2 10.3 10.4 "Lariam". The American Society of Health-System Pharmacists. Archived from the original on 7 January 2012. Retrieved 3 April 2011.
- ↑ 11.0 11.1 11.2 11.3 Schlagenhauf, P; Adamcova, M; Regep, L; Schaerer, MT; Rhein, HG (2010-12-09). "The position of mefloquine as a 21st century malaria chemoprophylaxis". Malaria Journal. 9: 357. doi:10.1186/1475-2875-9-357. PMC 3224336. PMID 21143906.
- ↑ "www.idsociety.org" (PDF). Archived (PDF) from the original on 2015-03-19.
- ↑ "Malaria - Chapter 3 - 2014 Yellow Book | Travelers' Health | CDC". Archived from the original on 2014-12-26.
- ↑ 14.0 14.1 14.2 14.3 Schlagenhauf, P. (1999). "Mefloquine for malaria chemoprophylaxis 1992-1998". Travel Med. 6 (2): 122–123. doi:10.1111/j.1708-8305.1999.tb00843.x. PMID 10381965.
- ↑ Tickell-Painter, M; Maayan, N; Saunders, R; Pace, C; Sinclair, D (30 October 2017). "Mefloquine for preventing malaria during travel to endemic areas". The Cochrane Database of Systematic Reviews. 10: CD006491. doi:10.1002/14651858.CD006491.pub4. PMC 5686653. PMID 29083100.
- ↑ 16.0 16.1 16.2 16.3 16.4 16.5 "Lariam medication guide" (PDF). Hoffman La Roche. Archived (PDF) from the original on 2 October 2013. Retrieved 27 September 2013.
- ↑ "www.cdc.gov" (PDF). Archived (PDF) from the original on 2015-02-09.
- ↑ "Malaria Information". Traveldoctor. Archived from the original on 28 June 2016. Retrieved 9 July 2016.
- ↑ Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Patel R, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S (2004). "Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number". Lancet. 364 (9432): 438–47. doi:10.1016/S0140-6736(04)16767-6. PMC 4337987. PMID 15288742.
- ↑ "Treatment of Malaria (Guidelines for Clinicians)" (PDF). CDC. Archived (PDF) from the original on 29 August 2017. Retrieved 17 August 2020.
- ↑ "www.accessdata.fda.gov" (PDF). Archived (PDF) from the original on 2016-03-04.
- ↑ "www.fda.gov" (PDF). Archived (PDF) from the original on 2014-06-30.
- ↑ "FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects". Archived from the original on 2019-12-13. Retrieved 2019-06-15.
- ↑ AlKadi, HO (2007). "Antimalarial drug toxicity: a review". Chemotherapy. 53 (6): 385–91. doi:10.1159/000109767. PMID 17934257.
- ↑ 25.0 25.1 "Mefloquine" (PDF). Medicines for the Prevention of Malaria While Traveling. Atlanta, Georgia: Centers for Disease Control and Prevention. 2019. Archived (PDF) from the original on 2020-08-03. Retrieved 2019-03-30.
- ↑ 26.0 26.1 González R, Hellgren U, Greenwood B, Menéndez C (2014). "Mefloquine safety and tolerability in pregnancy: a systematic literature review". Malaria Journal. 13: 75. doi:10.1186/1475-2875-13-75. PMC 3942617. PMID 24581338.
- ↑ Croft AM (2010). "Malaria: prevention in travellers". Clin Evid (Online). 2010. PMC 3217660. PMID 21418669.
- ↑ Schlagenhauf P, Blumentals WA, Suter P, et al. (2012). "Pregnancy and fetal outcomes after exposure to mefloquine in the pre- and periconception period and during pregnancy". Clin Infect Dis. 54 (11): e124–31. doi:10.1093/cid/cis215. PMC 3348951. PMID 22495078.
- ↑ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 3. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ↑ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 4. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ↑ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 6. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ↑ "Lariam product monogram" (PDF). Hoffman La Roche Limited. p. 18. Archived from the original (PDF) on 17 December 2011. Retrieved 24 April 2011.
- ↑ "Roche Submission to Committee Secretary Senate Foreign Affairs Australia". Archived from the original on 2020-01-24. Retrieved 2020-01-24.
- ↑ 34.0 34.1 "'It's not a benign drug - it has ruined my life'". Guardian News & Media Limited. 24 October 2002. Archived from the original on 3 August 2019. Retrieved 3 August 2019.
- ↑ Adams, Sharon (6 September 2017). "Cure or curse?". Canvet Publications Ltd. Legion Magazine. Archived from the original on 4 August 2019. Retrieved 4 August 2019.
- ↑ Hennequin, C.; Bourée, P.; Bazin, N.; Bisaro, F.; Feline, A. (1994). "Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine". Archives of Internal Medicine. 154 (20): 2360–2. doi:10.1001/archinte.1994.00420200116012. PMID 7944858.
- ↑ Speich, Rudolf; Haller, Alois (1994). "Central Anticholinergic Syndrome with the Antimalarial Drug Mefloquine". New England Journal of Medicine. 331 (1): 57–58. doi:10.1056/NEJM199407073310120. PMID 8202114.
- ↑ Overbosch D, Schilthuis H, Bienzle U, et al. (October 2001). "Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study". Clin. Infect. Dis. 33 (7): 1015–21. doi:10.1086/322694. PMID 11528574.
- ↑ 39.0 39.1 39.2 39.3 39.4 39.5 39.6 39.7 "Germany bans drug linked to brain damage, ramps up pressure on Canada". iPolitics. 9 December 2016. Archived from the original on 3 August 2019. Retrieved 3 August 2019.
- ↑ "Did Lariam send Cambridge student Alana Cutland to her death… and what anti-malarials should children take on their gap year?". Telegraph Media Group Limited. 3 August 2019. Archived from the original on 3 August 2019. Retrieved 3 August 2019.
- ↑ Haines, Avery (18 October 2019). "Canadian soldiers allege anti-malaria medication left them with intense rage, suicidal ideations". W5. Archived from the original on 16 April 2020. Retrieved 16 April 2020.
- ↑ Gofton TE, Al-Khotani A, O'Farrell B, Ang LC, McLachlan RS (June 2010). "Mefloquine in the treatment of progressive multifocal leukoencephalopathy". J Neurol Neurosurg Psychiatry. 82 (4): 452–455. doi:10.1136/jnnp.2009.190652. PMID 20562463. Archived from the original on 2012-03-21.
- ↑ McArdle JJ, Sellin LC, Coakley KM, Potian JG, Quinones-Lopez MC, Rosenfeld CA, Sutatos LG, Hognason K (June 2005). "Mefloquine inhibits cholinesterases at the mouse neuromuscular junction". Neuropharmacology. 49 (8): 1132–1139. doi:10.1016/j.neuropharm.2005.06.011. PMID 16081111.
- ↑ McArdle JJ, Sellin LC, Coakley KM, Potian JG, Hognason K (September 2006). "Mefloquine selectively increases asynchronous acetylcholine release from motor nerve terminals". Neuropharmacology. 50 (3): 345–353. doi:10.1016/j.neuropharm.2005.09.011. PMID 16288931.
- ↑ Zhou C, Xiao C, McArdle JJ, Ye JH (February 2006). "Mefloquine enhances nigral gamma-aminobutyric acid release via inhibition of cholinesterase". Journal of Pharmacology and Experimental Therapeutics. 317 (3): 1155–1160. doi:10.1124/JPET.106.101923. PMID 16501066. Archived from the original on 2021-08-28. Retrieved 2019-12-01.
External links
|External sites:
- Manufacturer's information
- Roche Medication Guide for Lariam Archived 2018-11-01 at the Wayback Machine
- Mefloquine (Lariam) Action, Clearinghouse for information on mefloquine news, research, toxicity
- Controversies and Misconceptions in Malaria Chemoprophylaxis for Travelers Archived 2011-12-17 at the Wayback Machine
- The position of mefloquine as a 21st century malaria chemoprophylaxis Archived 2015-07-08 at the Wayback Machine (Paper based on data collated for an F. Hoffmann-La Roche regulatory update)
- Crazy Pills - NYTimes Op-Ed Archived 2018-11-01 at the Wayback Machine
- The Lariam Files - Keith Epstein, Washington Post Archived 2017-02-09 at the Wayback Machine
- Pages using duplicate arguments in template calls
- Chemical articles without CAS registry number
- Articles without EBI source
- Chemical pages without ChemSpiderID
- Chemical pages without DrugBank identifier
- Articles without KEGG source
- Articles without UNII source
- Drugs missing an ATC code
- Drugboxes which contain changes to verified fields
- Drugboxes which contain changes to watched fields
- Articles with hatnote templates targeting a nonexistent page
- Articles with changed EBI identifier
- Webarchive template wayback links
- American inventions
- Antimalarial agents
- Chirality
- Chloroarenes
- Drug safety
- Hoffmann-La Roche brands
- Medical controversies
- Piperidines
- Quinolines
- Racemate
- Trifluoromethyl compounds
- World Health Organization essential medicines


text:
Ramsey McGrory, Vice President, Yahoo! North American Marketplaces and Head of the Right Media Exchange
Ramsey McGrory leads the Right Media Exchange business, and is also responsible for establishing and growing Yahoo!'s strategic use of data and insights for Yahoo! North American Marketplaces, whose mission is to leverage customer needs and marketplace dynamics to create winning strategies for the company's display, search and video solutions. Prior to these roles, Ramsey was on the Yahoo! U.S. Partnerships team and oversaw Yahoo!'s strategic relationships with major agency holding companies. He also led a team that drove participation and growth of the Right Media Exchange, which was acquired by Yahoo! in 2007.
With ten years of online media, banking and military experience, Ramsey brings a diverse background to Yahoo!. As a is a veteran of the Persian Gulf War and the early Internet days, he thrives in chaotic, fast-paced environments. Before joining Right Media, Ramsey worked in media and technology sales at DoubleClick and Excite. When there wasn't an Internet, he spent six years at NationsBank and in the Treasury and Derivatives Trading Groups at Citigroup, where he focused on Internet banking and credit/debt derivatives structuring. He was in the military from 1985-1993.
Ramsey received a Bachelor's degree in Economics from the University of the South, and a Master's degree in Management from Georgia Tech. He is based in New York City, where he is active in the William J. Clinton Foundation, sits on the board of The Jericho Project and co-founded Billions.org.
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text:
Supplementary Components01
Supplementary Components01. component for spatial legislation of Rock and roll activity, actomyosin contractility and epithelial PCP. Launch Actomyosin contractility in nonmuscle cells is certainly a central regulator of cell form change and tissues morphogenesis (Lecuit et al., 2011). Actin filaments Tilbroquinol as well as the myosin II electric motor, which includes two large chains, two important light chains and two regulatory light chains (RLC), assemble into contractile subcellular buildings and supracellular systems to drive different physiological procedures, including cell department, cell migration and tissues morphogenesis (Vicente-Manzanares et al., 2009). During advancement, dynamic actomyosin systems have been Tilbroquinol proven to mediate the collective behavior of the interacting network of cells. For instance, during gastrulation and vertebrate neural pipe closure, coordinated apical constriction, or contraction from the cell apex, leads to twisting and invagination of the epithelial cell sheet (Martin et al., 2009; Sawyer et al., 2010). During embryonic axis elongation in and anisotropic contractile makes mediate directional cell intercalation and convergent expansion (Blankenship et al., 2006; Rauzi et al., 2010; Skoglund et al., 2008). Nevertheless, systems underlying precise temporal and spatial control of actomyosin set up on the tissues size remain poorly understood. Emerging evidence signifies that planar cell polarity (PCP) signaling has an important function in spatial legislation of actomyosin contractility during vertebrate tissues morphogenesis. First uncovered in where it regulates polarity inside the plane from the wing epithelial cell sheet, Tilbroquinol an evolutionarily conserved primary PCP pathway regulates morphogenesis of both epithelial and non-epithelial tissue in vertebrates, including convergent expansion, neural pipe closure and PCP in the auditory sensory epithelium (Goodrich and Strutt, 2011). The primary PCP pathway indicators through the tiny GTPase RhoA and its own downstream effector Rho-associated kinases (Rock and roll), which phosphorylates myosin RLC to stimulate actomyosin contractility (Goodrich and Strutt, 2011). As well as the primary PCP pathway, both invertebrates and vertebrates make use of alternative systems for spatial legislation of actomyosin contractility to operate a vehicle planar polarized cell behavior. In convergent expansion, or germband expansion, is certainly powered by anisotropic junctional contractility separately of the primary PCP pathway and is probable mediated by cadherin-mediated mechanotransduction and junctional redecorating (Blankenship et al., 2006; Rauzi et al., 2010; Wieschaus and Zallen, 2004). In the mouse, hereditary evidence claim that a (encodes a conserved receptor-tyrosine kinase (RTK)-like molecule, which is certainly predicted to absence endogenous kinase activity as the invariant DFG theme essential for appropriate setting Tilbroquinol of ATP is certainly changed with ALG. In the mouse, as well as the primary PCP genes are necessary for a variety of developmental procedures likewise, including convergent expansion, neural pipe closure, PCP in the auditory sensory epithelium, and center and lung morphogenesis (Lu et al., 2004; Paudyal et al., 2010; Yen et al., 2009). Oddly enough, research in and zebrafish implicate vertebrate orthologs in both PCP and Wnt signaling and recommend different and occasionally conflicting features of in regulating PCP and Wnt signaling (Bin-Nun CXCR6 et al., 2014; Hayes et al., 2013; Borchers and Shnitsar, 2008; Wehner et al., 2011). Our latest function shows that regulates through modulation of junctional contractility PCP, but the root mechanism is certainly unknown. Right here we utilized cultured Madin-Darby canine kidney (MDCK) epithelial cells as well as the mouse auditory sensory epithelium to reveal the mechanisms where regulates actomyosin contractility during mammalian epithelial morphogenesis. We present that in MDCK cells, PTK7 stimulates Src kinase signaling at cell-cell connections, which Src signaling amounts are crucial for junctional Rock and roll2 localization. We after that present proof that SFK signaling at intercellular junctions regulates PCP in the mouse auditory sensory epithelium which PTK7-SFK signaling mediates tyrosine phosphorylation of junctional Rock and roll2. Outcomes knockdown in MDCK cells leads to flaws in cell form and actomyosin firm MDCK II cells exhibit PTK7 endogenously, which colocalizes with E-cadherin along cell-cell connections (Fig. 1A). When appearance was knocked down (KD) using brief hairpin RNAs (shRNAs), cells shown flattened morphology with an increase of apical surface and reduced elevation (Fig. 1A and C). The cell form defect had not been a secondary aftereffect of reduced cell thickness in confluent monolayers, as KD cell islands also shown flattened morphology and occupied bigger surface in comparison to control islands with similar amounts of cells (Fig. S1A). The localizations of E-cadherin, -catenin, plakoglobin as well as the.


text:
There's a new phone on the market called the "Freedom Phone", and the basic idea behind it is solid. It's a phone that gives you more privacy and less of the tracking from companies like Google and Apple, and I think most of us can agree that's a good thing. The problem is that the phone simply doesn't do that.
First, it's still running a version of Google's Android operating system. It's hard to build a new phone operating system from scratch, for sure, but using Google's is a tough angle to start from if you're trying to show how bad Google is. Plus, you still need to get service through Verizon or AT&T or similar. Those folks are essentially impossible to escape when it comes to mobile phones, but they can still watch everything you do.
Taking it further, though, this phone is just the UMIDIGI A9 Pro, rebranded as the "Freedom Phone" with some different apps preloaded, and being sold for 4x the cost. (note: it's been confirmed that it's a UMIDIGI phone, though whether it's the exact same specs as the A9 Pro is still being uncovered). If you want privacy, buying a cheap phone from a Chinese manufacturer isn't likely the best way to go.
The App Store
Perhaps of greater concern is the app store on the phone, and their hard push to make it completely uncensored. This means it will likely find plenty of spam and malware in the store soon, but we'll see what happens.
You can find plenty of articles about this phone, but here are two good ones to start with:
- The Freedom Phone Smells Like a Stupid, Cynical Grift
- MAGA-Branded 'Freedom Phone' Is a Black Box That Should Be Avoided at All Costs
So what to do?
If you're wanting privacy, and the Freedom Phone isn't a good solution, what should you do? You have a few good choices.
First, you can replicate pretty much all of the privacy-focused features on your own phone in a matter of minutes. Use Signal for messaging, DuckDuckGo for search, and Brave for browsing. Those apps are very privacy focused, and available to all Android and iPhone users already.
If the "censored" apps are a concern (like when Parler was removed from the Google Play Store), every Android phone allows you to sideload apps, so you're never limited anyhow. Sideloading comes with risks, though, so be careful if you go down that road.
If you really want to be secure, you can use a PinePhone instead. It uses a custom Linux-based operating system (not a trace of Google or Apple in there), and is likely the best bet for privacy-minded folks. With that custom OS and privacy comes some big downsides, though. In particular, most of your apps aren't available on there — that's the cost you need to be willing to pay.
Our diminishing privacy online is a major problem, and something that needs to be continually addressed, but this new phone is certainly not the answer.


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The D25980K 1-1/8" 80lb demolition hammer delivers a concrete pulverizing 52 joules of impact energy. The dependable and hard hitting German engineered mechanism, delivers long life. With its all metal housing and barrel, this demo hammer was meant for heavy-duty applications like floor trenching for pipe, breaking out stairs/risers, creating openings into shafts, breaking asphalt, loosening/breaking hard packed dirt/gravel/clay and confined space work when big power is needed. The Active Vibration Control® technology employed delivers reduced user vibration for less user fatigue and greater productivity.
• (1) D25980 Pavement Breaker
• (1) D259804 Hammer Truck Cart with bits
• (1) Flat Foot Plate for Hammer Truck
• (1) Pegged Foot Plate for Hammer Truck
• (1) Bull point chisel
• (1) 1" Cold Chisel
• (1) 3" Wide Chisel
•SHOCKS - Active Vibration Control reduces vibration felt by the user at the handles. A Perform and Protect feature.
•15 amp motor provides maximum power and overload protection
•Uses 1-1/8" Hex Demo Steel
•Rubber coated handles provide greater comfort and control
•Electronic soft start increases productivity by reducing bit walking
•Hammer Truck provides easy transportation of pavement breaker
•52 joules of impact energy provides maximum performance
•Compatible with DWH052K chiseling dust extraction system
•Impact Energy 61 ft/lbs
•15 Amps
•Loaded Speed (bpm) 900 bpm
DeWalt D25980K Heavy-Duty Pavement Breaker with Cart
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- Product Code: BTH978647807
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When Wi-Fi was in its infancy, it was looked at as a novelty. Often it was only installed in certain areas of a building to accommodate a few devices. Fast forward to today and you will find a very diverse group of "things" that use Wi-Fi. With wireless chipsets and the cost of compute dropping, wireless network connections have found their way into refrigerators, thermostats and exercise equipment, just to name a few.
Over the last 20 years, Wi-Fi has spread across all verticals and has become an essential part of the network infrastructure. One vertical I am very familiar with is education, specifically K-12. I started my career 17 years ago at a newly constructed high school. The high school was state-of-the-art at the time and included brand new VoIP phones, wireless access points and laptops that were Wi-Fi-capable. I remember installing the access points, not knowing anything about the technology, in what seemed to be an even arrangement across the entire school.
With no real requirements or design knowledge to back it up, this network ACTUALLY WORKED! Thinking of the demands thrown at today's school wireless network, I realize my first wireless network, left the way it was on day one, would melt off the ceiling.
Expectations in the wireless classroom change significantly from year to year. In the last five years, I have seen only enterprise-owned devices allowed on the network change into enterprise-owned devices plus bring your own device (BYOD). That easily doubled device counts on the wireless network with little change to infrastructure. Move forward a couple more years and we now see enterprise-owned devices include devices issued to students and BYOD. A classroom that once supported a couple of wireless devices transformed into a classroom with three to 40 devices, only to change again and now have to support 60 to 70 devices.
Laptops and tablets have been the predominant device in classrooms for the last handful of years. We are now seeing this change to include wireless displays, environmental monitors, lighting controls, public address equipment, alarms, bells and clocks. Many of these devices are considered life-safety devices and are critical for the safety of students and must remain usable at all times. Our once nice-to-have wireless network is now a critical component to the safety of students and staff across an entire school campus.
With every increasing device count and device diversity, our wireless networks have to be able to perform at a high level at all times. Efficiency and throughput gains in new Wi-Fi standards, such as Wi-Fi 6 (802.11ax), as well as overall growth in radio technology are critical to keep ALL devices functioning at peak performance. Getting devices on and off the air as quickly as possible should be the goal of all infrastructure manufacturers to meet the high expectations of end users.
A couple of questions to think about:
- What kind of unusual wireless network connected devices do you see in your schools?
- What instructional demands challenge your wireless network in your classrooms?
- What traditionally un-networked device do you have in your school that can't function without network connectivity now?
Go Deeper
Educational institutions among early adopters embracing Aruba Wi-Fi 6
Why OFDMA is a Magical Feature in 802.11ax
Deliver an Exceptional Experience with Aruba 802.11ax
Read My Other Blogs
Wi-Fi 6: Should You Believe the Hype?
Is Early Wi-Fi 6 Buy-In Worth It in The Budget-Conscience Public Sector?


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About the Volkswagen Taos
Volkswagen adds Taos to its growing crossover utility vehicle linuep. It wasn't too long ago that Volkswagen had one utility vehicle and that model was an undersized and understated compact Tiguan. Fast forward to 2018 and an all-new three-row midsize Atlas rolled out, followed closely by the second-generation and noticeably … Read more


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We ran out of stock of jumpers and some sizes of t-shirts a few weeks ago, if you've made an order in the last 6 weeks and you've not received it yet, please accept our apologies and please be patient, the order is in with our supplier in Edinburgh and you will be first to get sent out when we receive them. We should get them this week, so you should have them by next week.
If you make an order this week it should be with you in the next week or so, as we should have plenty of stock from our supplier this week.


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Diego's Umbrella
San Francisco's ambassadors of gypsy rock, Diego's Umbrella captures California's cultural multiplicity with enthusiasm, humor, decadence and a bit of fury.
These urban, gringo, gypsy mariachis have performed well over a thousand live shows, cloaked in sleek, often homemade, outfits and create an infectious good time for all walks of life. With a mix of Eastern European tradition, pop sensibility and punk rock energy, the band's unforgettable performance has visually and aurally captivated diverse audiences throughout the U.S. and Europe. Influenced heavily by flamenco, klezmer, rock, Balkan and Latin music, Diego's Umbrella has blurred musical lines to give the world what they call Gypsy Rock. Where Gogol Bordello meets Muse.
While the origins of Diego's Umbrella date back to the Fall of 2001, with the collaboration of founding members Vaughn Lindstrom (acoustic guitar, vocals) and Tyson Maulhardt (electric guitar), they officially hit the scene in 2005 with consistent west coast touring and the release of their first full-length album Kung Fu Palace. Violinist Jason Kleinberg came on board early in the project, Ben Leon (vocals, guitar) and Jake Wood (drums) teamed up in early 2009 and the 6-some was rounded out by new bass player Marcus Schmidt in 2011.
The Group has put out 3 studio albums including Viva la Juerga '07, Double Panther '09, and is currently working on their fourth full-length with Bay Area producers the Rondo Brothers, set for a mid 2012 release. They have been featured in major motion pictures, network television, and numerous documentaries, in addition to countless worldwide radio and print. The band recently signed with Ninth Street Opus, put out a two song single in the summer of 2011, tours throughout the year and has played numerous domestic festivals including Musikfest, High Sierra and Outside Lands, in addition to festivals across Europe.
"Both Diego's albums, Viva La Juerga and Double Panther, are exciting twists on popular gypsy fusion, encompassing DeVotchKa's dramatic sound and Gogol Bordello's intensity."
-Crawdaddy Magazine


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On Thursday, Bank of Japan (BOJ) board member Hitoshi Suzuki said that the central bank should allow super-long bond yields to rise moderately as part of efforts to make its stimulus program sustainable.
Under its yield curve control policy, the BOJ seeks to keep short-term interest rates at around -0.1% and 10-year bond yields at around zero as part of efforts to revive the economy with low borrowing costs.
But years of ultra-low rates have strained financial institutions' profits, stoking fears that they may not earn enough to boost lending and help support the economy.
"Allowing the super-long end of the yield curve to steepen moderately, while keeping 10-year bond yields around zero, would help financial institutions earn more profits," Suzuki told business leaders in Fukushima, northeastern Japan.
"As such, this will be desirable from the standpoint of maintaining financial system stability, as our monetary easing is prolonged," he said.
Suzuki also said the BOJ must seek to make its policy structure "flexible and sustainable," including its purchases of hazardous assets such as exchange-traded funds.
His remarks mark a growing concern among policymakers over the rising costs of the BOJ's monetary easing, which has failed to fire up inflation to its elusive 2% inflation target.


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User Details
- User Since
- May 13 2014, 8:36 PM (489 w, 2 d)
May 10 2016
Having tested it after randomly happening upon the issue I've found it is caused by every piece of clothing (to some degree or another) other than underwear or the default clothing when you're not wearing anything in the inventory slot. Vests and backpacks also add to the clipping, but helmets for sure don't interact with the scope.
Best guess: the Zafir's camera position (that you change to when aiming down the sights) for the RCO and ARCO is put too far back on the weapon and is clipping into the shoulder, especially when moving to the right which causes the biggest clipping issue of all directional movements. I assume this has to do with some design decision to keep the Zafir's iron sights still visible in any optic with dual purposes built in. Short range holo optics have no issue and long range sights like the Thermal sight for machine guns do not have issues with this either.
Testing on the MRCO yielded nothing for me, oddly enough, but the image definitely suggests there's something to check with it.


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Portrait of Young Girl Feeding Ducks Along the Ohio River
Helen Feeding the Ducks by the Mike Fink Resturant, oil on canvas, 3' x 4', October 2007
Tom started this work as his Tall Stacks Painting. Every three or four years Cincinnati, Ohio hosts 15 riverboats for four days of boating and music. Tom decided to paint his daughter with the main symbols of Tall Stacks, a paddle wheel and the pier of the Suspension Bridge. Tom grew up on the Ohio River and work on this paddle wheel while in high school. He later worked for Captain Beatty on various salvage jobs on the Ohio. His family had a house boat docked behind the restaurant and he spent many a night studying and fishing off the bow. The singing of the cars driving across the Suspension Bridge played ever in the backgroound. Tom changed the water's edge to the pavers used across the river at the Cincinnati public landing. The background is just as it is in 2004. You cna just barely see Paul Brown Stadium just to the left of the stern wheel. The Mike Fink was moved to dry dock in March of 2008 and if all goes well will return soon.
Painted for Cincinnati's Tall Stacks Celebration 2007, every four years the Cincinnati River front transformed into a nostalgic by gone era with old time riverboats lining the riverbank. Long weekend festivities, river cruises, fireworks and education about river lore take place along both sides of the Ohio River. In the past, Tom painted nostalgic views of the river on location amongst the crowds but this year he set up his easel in front of the Mike Fink's Restaurant, the place of his first job. He combined the best of both sides of the river to show a modern view but still indicative of little change of the view since 1864 when the Robeling Suspension bridge opened at the end of the Civil War.
Photo montage for the work
Other Children's Portraits


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Andy Grabowski
Director of Strategic Development
As the Director of Strategic Development, Andy focuses on identifying and evaluating business growth opportunities, operational partnerships, and internal efficiencies. Andy helps us find new ways to leverage our IT systems and processes and keep us as productive and efficient as possible.
He joins Intervine with over 8+ years sourcing experience with wine, beer, and spirits at a major domestic airline. Prior to his work in Procurement, Andy utilized all his business and finance skills as a Management Consultant with Gibson Consulting and Accenture supporting companies ranging in size from startups to Fortune 500. Andy has his B.S. in Finance from Eastern Illinois University.
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With plenty to see and do in the area, Cannon Beach is a great spot for a romantic getaway or families on their annual holidays. Walk along the sandy beach with the iconic Haystack Rock, with gorgeous coastline views set within a charming village by the sea.
Location of Cannon Beach
Located on the west coast of Oregon, Cannon Beach is a popular destination due it offering both adventure and relaxation. You will be able to enjoy great beach access, hiking trails and beautiful landscapes, unique art galleries, high-end hotels and delicious restaurants.
Haystack Rock is an icon for Cannon Beach, especially as it is considered to be the world's third-largest monolith. This is a great photo opportunity spot as the sand, water and sky combine to create beautiful scenery. You may even have the chance to see puffins and many other sea creatures who inhabit this particular area. Many of the hotels and bed and breakfasts often offer views over the coastline and this incredible rock. You should then explore Ecola State Park which is home to two sandy beaches as well as plenty of hiking trails, areas for picnics and plenty of spots for camping. At the Ecola State Park, you will have incredible coastal views. Any history buffs will have the chance to walk the same trails of Lewis and Clark. You can also take one of the hiking trails to Indian Beach which is a great spot for Oregon Coast Surfers. Explore some of the wonderful caves at Hug Point when the low tide is in. Only three miles south of Cannon Beach, you will be able to find sea caves, a small waterfall and the remains of the old cliff-side roadway, making for some spectacular sights.
You will find a variety of unique and interesting art galleries throughout Cannon Beach, each carrying different media from fine art to affordable crafts. A lot of the works that can be found in the art galleries are made by local artists and craftsmen. If you want fine paintings, sculptures and ceramics then the Northwest by Northwest Gallery is a great place to stop by. For fine art, paintings and cast bronze sculptures you should stop by the Bronze Coast Gallery. If more colourful and fun art or fine crafts are up your alley, then the Dragon Fire Studio and Gallery is the right choice for you. Another great pastime is to explore the shops of Cannon Beach, often found in the buildings along with Spruce and Hemlock beach. Each shop has fun and unique items for you to browse. Souvenirs and delicious sea saltwater taffy and old-fashioned sweets are best to get from Bruce's Candy Kitchen. If you want to find some unique toys or souvenirs to take home, Gepetto's Toy Shoppe is a great place to stop by. You may even want to get something a bit more festive in the year-round Christmas store called Yuletide Christmas Shop.
For some more unique activities, you should check out live glassblowing at the Icefire Glassworks. You will be able to get up close and learn about the wonderful and complicated art of glassblowing. You will get a chance to shop for unique pieces and watch as new glass pieces are being created in the shop by the artists. If you are a bit partial to whiskey then you should head over to the Cannon Beach Distillery for a delectable tasting. Using top of the line ingredients to distil, mature and bottle the whiskey, you will be able to enjoy each sip neat and at room temperature. None of the whiskeys features dyes, sweeteners or artificial ingredients, so enjoy sipping on some premium flavours and watch the world go by with coastline views. If you want to learn a new skill on your trip, look no further than enjoying a culinary experience at EVOO. You will be able to have dinner, a demonstration and a cooking lesson in your visit. As the dinner is prepared you will be given tips on preparing food and how to serve as a chef. The menu is never the same as it changes seasonally, but you will be able to enjoy a three-course meal that has a paired wine for every course, plus dessert and coffee to finish the evening.
Where to Stay
Cannon Beach has plenty of options to stay during your visit, especially with a great selection of oceanfront lodging that give you beautiful coastal views across the beach and maybe even featuring Haystack Rock. With resorts, classic hotels, home rentals and campsites, Cannon Beach accommodates all types of travellers, be it couples, families, large groups and even pets. The Wayside Inn is a great spot to stay for ocean views, as well as being set at the quieter end of Cannon Beach, having access to local grocery shops, coffee shops and bakeries. It is only a short walk to the centre of Cannon Beach where you will find a variety of restaurants, galleries and shops. The Sea Sprite Guest Lodgings have two properties that are perfect for families, honeymoons or even hosting intimate weddings. Both properties offer ocean views and have unique rooms that offer the comforts and conveniences of being at home. If you are looking for a bit more privacy with a holiday rental property, Anchor's Retreat is a great option. With five bedrooms and the capacity for ten people, you will be able to look out over the beach on the wraparound deck and enjoy delicious meals in the large kitchen.
When to Go to Cannon Beach
Being a seaside town, the best time to visit Cannon Beach will be when you can enjoy the hot-weather activities that the area has to offer. The best time to visit is between late July and early September, with August usually having the peak of hot weather.
How to Get to Cannon Beach
You can get to Cannon Beach from Portland Airport, with plenty of shuttle buses to pick and drop you off.
Check out the best flight deals.


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Getting into your Morning Grove….
I've always been a morning person. I don't remember sleeping much as a teenager either. That was many years ago now! During my early twenties I had multiple shift jobs and dreaded the alarm going off to start the day. Fast forwarding into pregnancy and the early infant days I lost track of my morning and evening routine being exhausted…View Post


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A sports fan take on the world of sports. Out is what the media wants me to think, in is what people should be following. Listed Top 75 Sports Blog by Social Animal https://socialanimal.com/blog/best-sports-blogs/
Who am I?
Follow me on Twitter: @lhd_on_sports
Wednesday, December 19, 2018
Sportsman of the Week Ending 12/16/2018
Posted by longhorndave at 9:21 PM
Labels: Arizona State, College Football, Fresno State, Las Vegas Bowl, LHD_PotW, Mountain West Conference, NCAA, Pac 12
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"Camera Crew" Figure #3 "Boom Operator" For 1:24 Scale Diecast Models by American Diorama
- Brand New 1/24 scale model of "Camera Crew" Figure #2 "Crew Holding Reflector" For 1:24 Scale Diecast Models by American Diorama.
- Officially licensed product.
- Comes in a blister pack.
- Hand painted poly-resin material.
- Does not come with the vehicle or other figures shown.
- Fits all 1/24 scale buildings and dioramas.
- Figure is approximately 3.25 inches tall.


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Slab Sicilian Street Food
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Slab Sicilian Street Food
25 Preble St, Portland, 04101
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Slab Sicilian Street Food
Slab Sicilian Street Food is located in the old Portland Public Market building on Preble Street, a convenient location in beautiful downtown Portland, Maine. Nationally-acclaimed for their unique spin on Sicilian street food and best known for our namesake 'slab' pizza, a favorite of locals, and a must-taste tourist experience. Tap takeovers, food events, and live music are popular at Slab, especially in the summer on their outside patio. #feedkidsmaine
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text: It's hard to believe that only one week ago the Triangle area had a massive snow storm, and yet we are only a few weeks away from graduation. With thousands of graduates about to enter the job market, it's time to take pause and ask ourselves, are we ready to face life from beyond the campus walls? Many of us will leave shortly with newly minted job offers currently in hand. Many will take a job temporarily in any field just to have a job until the economy improves and enhances our chances of entering the field of our choice. Many will also go to graduate school as it seems like the next logical choice. But is it smart to immediately enter graduate school without at least a few years experience? From the experts in job placement and career services that I have talked to the job market is still weak right now. Should we be worried, or is this the same problem every graduate faces upon the thought of reality? What are your thoughts?


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Benny Tai: movement too big2014.10.07
OCCUPY Central (佔領中環) organiser Benny Tai Yiu-ting (戴耀廷 ) admitted that no single group can now dominate the movement as citizens have joined the civil disobedience campaign.
Tai made the remark after a group of Occupy volunteers tried to remove some of the metal barricades outside the government headquarters in Tamar (添馬艦).
Others were dismayed at this action and claimed the barriers were put up to prevent the police from clearing the site.
"Through mutual trust and discussion among ourselves, with the same object, all these problems can be solved," Tai said.
He said there are many community groups and citizens who joined voluntarily.
Tai said that they will think about how to prolong the campaign and get citizens to accept their way.
Meanwhile, the dean of the Chinese University's Faculty of Medicine (中文大學醫學院), Francis Chan Ka-leung (陳家亮), revealed in a letter on the internet that some of the medical students who had joined the protests called him at 3am to ask for help and counselling.
"I have been in unspeakable agony with all the developments," Chan said.
"When I saw the class boycott turning into a full-scale confrontation between police and protesters and when the police fired tear gas canisters into the crowd, my heart sank.
"There were several instances when my telephone conversations with students were suddenly cut ... my anxiety had reached a point that I felt like an ant in a hot frying pan.
"As of this point in time, I am glad that no students were injured or arrested.
"I exhort them to make use of this opportunity to reflect on how to pursue an ideal, just and righteous society."
Chief Executive (行政長官) Leung Chun-ying (梁振英) and Chief Secretary for Administration (政務司司長) Carrie Lam Cheng Yuet-ngor (林鄭月娥) appeared in a press briefing at Government House (禮賓府) to offer an olive branch to the protesters. But that offer was rejected after anti-Occupy protesters attacked students and the police were accused of reacting slowly.
He appointed Lam to start a dialogue on political reform with Federation of Students' (專上學生聯會) representatives as soon as possible.
(The Standard, Qi Luo and Mary Ann Benitez, 3 October, 2014)


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Call me to schedule a FREE consultation!
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Kristina is an amazing source of knowledge, a true wise woman and an amazing support to her community. Having worked beside her on occasion, she is a natural with people. She works with a range of modalities and is excellent in each one.
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