text:
Who the hell is Chuck E and why is he in love?
DURING the Countdown era Rickie Lee Jones' Chuck E's in Love was always a bit of an oddity.
Rickie's delivery was whimsical and warm and the film clip featured her in a jaunty beret as I recall.
But who the hell was Chuck E? And why was he in love?
Of course, when she played Jambalaya tent at Bluesfest on Friday, THAT'S the song that everybody wanted to hear.
Apparently, Chuck E was a friend of Jones and her partner at the time Tom Waits.
Wait's got off the phone one day from their friend and supposedly uttered the line 'Chuck E's in Love'.
There was a lot of love for Rickie Lee on Friday and she looked genuinely chuffed to find an audience here in Australia after all these years.
On the way to Chuck E's in Love, Jones played another big hit in the form of Horses, which was given a rousing reception and enthusiastic sing along thanks to Darly Braithwaite's cover of it many years ago.
Jones explained the song was written for her daughter, who is now well into her adulthood.
Funny how the meanings behind songs don't always play out the way you think they might.


text:
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Healthhealth (helth),USA pronunciation n.
health′ward, adj., adv.
- the general condition of the body or mind with reference to soundness and vigor: good health; poor health.
- soundness of body or mind;
freedom from disease or ailment: to have one's health; to lose one's health.
- a polite or complimentary wish for a person's health, happiness, etc., esp. as a toast: We drank a health to our guest of honor.
- vigor;
vitality: economic health.
Andand (and; unstressed ənd, ən, or, esp. after a homorganic consonant, n),USA pronunciation conj.
- (used to connect grammatically coordinate words, phrases, or clauses) along or together with;
as well as;
in addition to;
moreover: pens and pencils.
- added to;
plus: 2 and 2 are 4.
- then: He read for an hour and went to bed.
- also, at the same time: to sleep and dream.
- then again;
repeatedly: He coughed and coughed.
- (used to imply different qualities in things having the same name): There are bargains and bargains, so watch out.
- (used to introduce a sentence, implying continuation) also;
then: And then it happened.
- [Informal.]to (used between two finite verbs): Try and do it. Call and see if she's home yet.
- (used to introduce a consequence or conditional result): He felt sick and decided to lie down for a while. Say one more word about it and I'll scream.
- but;
on the contrary: He tried to run five miles and couldn't. They said they were about to leave and then stayed for two more hours.
- (used to connect alternatives): He felt that he was being forced to choose between his career and his family.
- (used to introduce a comment on the preceding clause): They don't like each other--and with good reason.
- [Archaic.]if: and you please.Cf. an2.
- and so forth, and the like;
and others;
et cetera: We discussed traveling, sightseeing, and so forth.
- and so on, and more things or others of a similar kind;
and the like: It was a summer filled with parties, picnics, and so on.
- an added condition, stipulation, detail, or particular: He accepted the job, no ands or buts about it.
- conjunction (def. 5b).
Safetysafe•ty (sāf′tē),USA pronunciation n., pl. -ties.
- the state of being safe;
freedom from the occurrence or risk of injury, danger, or loss.
- the quality of averting or not causing injury, danger, or loss.
- a contrivance or device to prevent injury or avert danger.
- Also called lock, safety catch, safety lock. a locking or cutoff device that prevents a gun from being fired accidentally.
- the action of keeping safe.
- [Football.]
- an act or play in which a player on the offensive team is tackled in his own end zone or downs the ball there, or in which the ball goes out of bounds on a fumble, having last been in bounds in or over the end zone and having last been in the possession of an offensive player. Cf. touchback.
- an award of two points to the opposing team on this play.
- Also called safety man. a player on defense who lines up farthest behind the line of scrimmage.
- [Baseball.]a base hit, esp. a one-base hit.
- a condom.
- [Obs.]close confinement or custody.
Inin (in),USA pronunciation prep., adv., adj., n., v., inned, in•ning.
- (used to indicate inclusion within space, a place, or limits): walking in the park.
- (used to indicate inclusion within something abstract or immaterial): in politics; in the autumn.
- (used to indicate inclusion within or occurrence during a period or limit of time): in ancient times; a task done in ten minutes.
- (used to indicate limitation or qualification, as of situation, condition, relation, manner, action, etc.): to speak in a whisper; to be similar in appearance.
- (used to indicate means): sketched in ink; spoken in French.
- (used to indicate motion or direction from outside to a point within) into: Let's go in the house.
- (used to indicate transition from one state to another): to break in half.
- (used to indicate object or purpose): speaking in honor of the event.
- in that, because;
inasmuch as: In that you won't have time for supper, let me give you something now.
- in or into some place, position, state, relation, etc.: Please come in.
- on the inside;
- in one's house or office.
- in office or power.
- in possession or occupancy.
- having the turn to play, as in a game.
- [Baseball.](of an infielder or outfielder) in a position closer to home plate than usual;
short: The third baseman played in, expecting a bunt.
- on good terms;
in favor: He's in with his boss, but he doubts it will last.
- in vogue;
in style: He says straw hats will be in this year.
- in season: Watermelons will soon be in.
- be in for, to be bound to undergo something, esp. a disagreeable experience: We are in for a long speech.
- in for it, [Slang.]about to suffer chastisement or unpleasant consequences, esp. of one's own actions or omissions: I forgot our anniversary again, and I'll be in for it now.Also,[Brit.,] for it.
- in with, on friendly terms with;
familiar or associating with: They are in with all the important people.
- located or situated within;
internal: the in part of a mechanism.
- [Informal.]
- in favor with advanced or sophisticated people;
stylish: the in place to dine; Her new novel is the in book to read this summer.
- comprehensible only to a special or ultrasophisticated group: an in joke.
- well-liked;
included in a favored group.
- inward;
inbound: an in train.
- plentiful;
- being in power, authority, control, etc.: a member of the in party.
- playing the last nine holes of an eighteen-hole golf course (opposed to out): His in score on the second round was 34.
- Usually, ins. persons in office or political power (distinguished from outs).
- a member of the political party in power: The election made him an in.
- pull or influence;
a social advantage or connection: He's got an in with the senator.
- (in tennis, squash, handball, etc.) a return or service that lands within the in-bounds limits of a court or section of a court (opposed to out).
v.t. Brit. [Dial.]
- to enclose.
Thethe1 (stressed ᵺē; unstressed before a consonant ᵺə;
unstressed before a vowel ᵺē),USA pronunciation definite article.
- (used, esp. before a noun, with a specifying or particularizing effect, as opposed to the indefinite or generalizing force of the indefinite article a or an): the book you gave me; Come into the house.
- (used to mark a proper noun, natural phenomenon, ship, building, time, point of the compass, branch of endeavor, or field of study as something well-known or unique):the sun;
the Alps;
theQueen Elizabeth;
the past; the West.
- (used with or as part of a title): the Duke of Wellington; the Reverend John Smith.
- (used to mark a noun as indicating the best-known, most approved, most important, most satisfying, etc.): the skiing center of the U.S.; If you're going to work hard, now is the time.
- (used to mark a noun as being used generically): The dog is a quadruped.
- (used in place of a possessive pronoun, to note a part of the body or a personal belonging): He won't be able to play football until the leg mends.
- (used before adjectives that are used substantively, to note an individual, a class or number of individuals, or an abstract idea): to visit the sick; from the sublime to the ridiculous.
- (used before a modifying adjective to specify or limit its modifying effect): He took the wrong road and drove miles out of his way.
- (used to indicate one particular decade of a lifetime or of a century): the sixties; the gay nineties.
- (one of many of a class or type, as of a manufactured item, as opposed to an individual one): Did you listen to the radio last night?
- enough: He saved until he had the money for a new car. She didn't have the courage to leave.
- (used distributively, to note any one separately) for, to, or in each;
a or an: at one dollar the pound.
Computercom•put•er (kəm pyo̅o̅′tər),USA pronunciation n.
com•put′er•like′, adj.
- Also called processor. an electronic device designed to accept data, perform prescribed mathematical and logical operations at high speed, and display the results of these operations. Cf. analog computer, digital computer.
- a person who computes;
Roomroom (ro̅o̅m, rŏŏm),USA pronunciation n.
- a portion of space within a building or other structure, separated by walls or partitions from other parts: a dining room.
- rooms, lodgings or quarters, as in a house or building.
- the persons present in a room: The whole room laughed.
- space or extent of space occupied by or available for something: The desk takes up too much room.
- opportunity or scope for something: room for improvement; room for doubt.
- status or a station in life considered as a place: He fought for room at the top.
- capacity: Her brain had no room for trivia.
- a working area cut between pillars.
- to occupy a room or rooms;
Thatthat (ᵺat; unstressed ᵺət),USA pronunciation pron. and adj., pl.those;
- (used to indicate a person, thing, idea, state, event, time, remark, etc., as pointed out or present, mentioned before, supposed to be understood, or by way of emphasis): That is her mother. After that we saw each other.
- (used to indicate one of two or more persons, things, etc., already mentioned, referring to the one more remote in place, time, or thought;
opposed to this): This is my sister and that's my cousin.
- (used to indicate one of two or more persons, things, etc., already mentioned, implying a contrast or contradistinction;
opposed to this): This suit fits better than that.
- (used as the subject or object of a relative clause, esp. one defining or restricting the antecedent, sometimes replaceable by who, whom, or which): the horse that he bought.
- (used as the object of a preposition, with the preposition standing at the end of a relative clause): the farm that I spoke of.
- (used in various special or elliptical constructions): fool that he is.
- at that:
- in spite of something;
nevertheless: Although perhaps too elaborate, it seemed like a good plan at that.
- in addition;
besides: It was a long wait, and an exasperating one at that.
- that is, (by way of explanation, clarification, or an example);
more accurately: I read the book, that is, I read most of it.Also, that is to say.
- that's that, there is no more to be said or done;
that is finished: I'm not going, and that's that!
- with that, following that;
thereupon: With that, he turned on his heel and fled.
- (used to indicate a person, place, thing, or degree as indicated, mentioned before, present, or as well-known or characteristic): That woman is her mother. Those little mannerisms of hers make me sick.
- (used to indicate the more remote in time, place, or thought of two persons, things, etc., already mentioned;
opposed to this): This room is his and that one is mine.
- (used to imply mere contradistinction;
opposed to this): not this house, but that one.
- that way, [Informal.]in love or very fond of (usually fol. by about or for): The star and the director are that way. I'm that way about coffee.
- (used with adjectives and adverbs of quantity or extent) to the extent or degree indicated: that much; The fish was that big.
- to a great extent or degree;
very: It's not that important.
- [Dial.](used to modify an adjective or another adverb) to such an extent: He was that weak he could hardly stand.
- (used to introduce a subordinate clause as the subject or object of the principal verb or as the necessary complement to a statement made, or a clause expressing cause or reason, purpose or aim, result or consequence, etc.): I'm sure that you'll like it. That he will come is certain. Hold it up so that everyone can see it.
- (used elliptically to introduce an exclamation expressing desire, a wish, surprise, indignation, or other strong feeling): Oh, that I had never been born!

subset: commoncrawl


text:
Rowsley, KOP and Sunmoon TODAY!
- Technically, the STI see immediate support at 3,275, with upside resistance pegged at 3,320.
- Not considering the 1 time gain from sale, SPH revenue fell as expected in my previous email
For investing: may consider bank shares, namely DBS. Property counters such as Wheelock and Capitaland too
For trading: personally I am watching Rowsley, KOP and sunmoon
- FY17 net profit grew 32% to $350.1m, mainly lifted by a $149.7m divestment gain arising from a 33% stake sale in online classified site 701Search.
- Otherwise, full-year core earnings of $200.4m (-24.5%) missed street forecasts.
- Operating revenue of $1.05b (-8.8%) continued to be pressured by the core media business (-13%).
- EBIT margin contracted to 19.5% (-7ppt), on impairment charges totalling $60.6m.
- Final and special DPS shaved to 9¢ (4Q16: 11¢), bringing FY17 DPS to 15¢ (FY16: 18¢).
- Group reducing headcount further and expects to incur retrenchment costs of $13m in 1QFY18.
- Last traded at 19.1x forward P/E and 2.7% dividend yield.
*Duty Free International
- 2QFY18 net profit crept 1.6% higher to RM14.1m, lifted by a RM1.6m fair value gain on option.
- This brought 1HFY18 earnings to RM29.1m (-13.6%), or 45% of full-year street estimate.
- Quarter revenue slipped 5.5% to RM148.3m, on lower demand due to the GST imposition at border outlets and duty free zones.
- Declared second interim DPS of 0.5¢ (2QFY17: nil).
- Trades at 13.9x forward P/E.
*TEE International
- Slumped into a 1QFY18 net loss of $0.9m (1QFY17: $0.6m profit) on gross margin compression.
- Revenue rose 9.6% to $70.1m from higher progressive sales from ongoing development properties, but gross margin contracted to 10.1% (-1.2ppt).
- Bottom line was further impacted by a 221.3% spike in selling & distribution expenses on promotional activity, as well as absence of tenant compensation (1QFY17: $0.4m) and FX gain (1QFY17: $0.2m).
- NAV/share at $0.189.
*TEE Land
- 1QFY18 net profit dived 96.3% to $22,000.
- Revenue surged 88.4% to $26m on higher progressive revenue from development projects Hibre 28, 183 Longhaus and Have Avenue project.
- But gross profit narrowed to 16.3% (-12.1ppt) on a shift in sales mix.
- Earnings fizzled on a 225% spike in selling & distribution costs from promotional expenses incurred and lower associate contribution (-20.3%).
- NAV/share at $0.352.
- 32.5% owned Nanjing Puzhen Rail Transport secured three metro train car supply contracts worth Rmb2.37b.
- The contracts are slated for delivery between Jun '18 and Mar '21.
- The counter is a beneficiary of China's push to develop and expand urban rail transit systems to meet the needs of urbanisation.
- Last traded at 11.9x forward P/E.
- Proposed placement of 500m new shares (8.7% enlarged share capital) at 0.8¢ to two parties.
- The placees include management consultancy firm, Summit Planners Advisory Group, and non-exec director, Liu Song.
- Net proceeds of $3.9m intended to support M&A of WE Crowdfunding and working capital.
- Proposed 11% investment in a cross-platform Malaysian B2B commerce solution provider, Boostorder, for RM2.5m.
- The investment is synergistic to the group's existing proprietary software and customer base.
- Last traded at 1.2x trailing P/E.
- Entered into an agreement to dispose a 60-year leasehold, underutilised cold storage and office at 5 Second Chin Bee Road for $7.8m.
- The sale price is at a 6% discount to a market valuation done back in 2015, and the group estimates a disposal gain of $4.2m.
- Net proceeds from the disposal will be used to pare debt and for working capital.
News for today 12/10/2017:
- Five Things You Need to Know to Start Your Dayhttps://www.bloomberg.com/news/articles/2017-10-11/five-things-you-need-to-know-to-start-your-day-j8nm4fkk
- IMF calls for fiscal policies that tackle rising inequality http://www.straitstimes.com/business/imf-calls-for-fiscal-policies-that-tackle-rising-inequality?xtor=CS3-18
- Oil prices settle up on demand forecasts, Kurdistan tensions http://www.businesstimes.com.sg/energy-commodities/oil-prices-settle-up-on-demand-forecasts-kurdistan-tensions
- Gold extends gains after latest Fed meeting minutes http://www.businesstimes.com.sg/energy-commodities/gold-extends-gains-after-latest-fed-meeting-minutes?xtor=CS3-25
- Dow, S&P 500, Nasdaq at record highs, extending rally http://www.straitstimes.com/business/companies-markets/dow-sp-500-nasdaq-at-record-highs-extending-rally?xtor=CS3-18
- 'Many' Fed members favour December rate hike: Minutes http://www.straitstimes.com/business/companies-markets/many-fed-members-favour-december-rate-hike-minutes?xtor=CS3-18; Federal Reserve should raise policy rate to 2.5% over two years: Williams http://www.businesstimes.com.sg/government-economy/federal-reserve-should-raise-policy-rate-to-25-over-two-years-williams?xtor=CS3-25
- US carrier drills with Japanese navy around Okinawa, south-west of Korean peninsula http://www.straitstimes.com/asia/east-asia/us-carrier-drills-with-japanese-navy-around-okinawa-south-west-of-korean-peninsula?xtor=CS3-18
- Condo, private apartment rents slip 0.1% in September; HDB rents slide 0.9% http://www.straitstimes.com/business/property/condo-private-apartment-rents-slip-01-in-september-hdb-rents-slide-09?xtor=CS3-18
- Women's CPF savings go up, narrowing gender gap http://www.straitstimes.com/singapore/manpower/womens-cpf-savings-go-up-narrowing-gender-gap?xtor=CS3-18
- Collective sales: Why some owners missed out http://www.straitstimes.com/business/property/collective-sales-why-some-owners-missed-out?xtor=CS3-18
- Sim Lim Square forms committee in first attempt http://www.straitstimes.com/business/property/sim-lim-square-forms-committee-in-first-attempt?xtor=CS3-18
- Many in finance, accounting 'not future-ready' http://www.straitstimes.com/business/companies-markets/many-in-finance-accounting-not-future-ready?xtor=CS3-18
Stocks to watch today 12/10/2017:
- Accrelist last close $0.007, 52wk high/low $0.008/$0.004 - Company to raise S$4m via proposed share placement to support e-medical and e-wallet initiatives http://www.businesstimes.com.sg/companies-markets/accrelist-to-raise-s4m-via-proposed-share-placement-to-support-e-medical-and-e?xtor=CS3-25
- Banyan Tree last close $0.645, 52wk high/low $0.68/$0.36 - Company marks homecoming with resort in Mandai http://www.businesstimes.com.sg/companies-markets/banyan-tree-marks-homecoming-with-resort-in-mandai?xtor=CS3-25
- Frasers Centrepoint last close $2.08, 52wk high/low $2.17/$1.47 - Company acquires three German companies http://www.straitstimes.com/business/companies-markets/frasers-centrepoint-acquires-three-german-companies?xtor=CS3-18
- Genting Singapore last close $1.18, 52wk high/low $1.215/$0.74 - Company markets debut Samurai bonds http://www.straitstimes.com/business/companies-markets/genting-singapore-markets-debut-samurai-bonds?xtor=CS3-18
- Lafe Corp last close $0.90, 52wk high/low $0.92/$0.305 - Chairman's buyout offer goes unconditional http://www.straitstimes.com/business/companies-markets/lafe-corp-chairmans-buyout-offer-goes-unconditional?xtor=CS3-18
- New Silkroutes last close $0.42, 52wk high/low $1.09/$0.35 - Company buys The Dental Hub's three clinics; auditor flags prepayments to a supplier http://www.straitstimes.com/business/companies-markets/new-silkroutes-buys-the-dental-hubs-three-clinics-for-32m-in-shares-to?xtor=CS3-18
- SPH last close $2.69, 52wk high/low $3.78/$2.54 - Company speeds up staff cuts; posts 32% rise in full-year net profit http://www.straitstimes.com/business/companies-markets/sph-posts-32-rise-in-net-profit-to-speed-up-staff-cuts?xtor=CS3-18; SPH revamps for better footing in digital information age http://www.businesstimes.com.sg/companies-markets/sph-revamps-for-better-footing-in-digital-information-age?xtor=CS3-25
- Spackman last close $0.121, 52wk high/low $0.199/$0.097 - Company buys Korean film production company Take Pictures for $3.9m in shares, cash http://www.straitstimes.com/business/companies-markets/spackman-buys-korean-film-production-company-take-pictures-for-39m-in?xtor=CS3-18
- SIIC last close $0.525, 52wk high/low $0.655/$0.45 - Company receives green light for upgrading, expansion of Wuhan water plant http://www.businesstimes.com.sg/companies-markets/siic-receives-green-light-for-upgrading-expansion-of-wuhan-water-plant?xtor=CS3-25


text:
A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects
Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.
In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC0–168h)].
Steady-state exposure of semaglutide was similar for both populations: AUC0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (Cmax) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC0–168h ERR 1.11; Cmax ERR 1.14). Dose-dependent increases in AUC0–168h and Cmax occurred in both populations. Accumulation was as expected, based on the half-life (t1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.
The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.
Novo Nordisk A/S, Denmark.
Trial registration
ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.
KeywordsGLP-1 receptor agonist Japanese subjects Pharmacodynamics Pharmacokinetics Semaglutide Type 2 diabetes
The prevalence of type 2 diabetes (T2D) and prediabetes has increased significantly since the 1980s in the general Japanese population. The rising incidence of obesity and a marked decline in physical activity have both exerted an influence on this increasing T2D trend [1]. Despite the availability of numerous glucose-lowering drugs, there remains an unmet need for effective diabetes treatment [2], as a significant proportion of individuals with T2D are still not achieving recommended glycemic targets (e.g., HbA1c < 7.0% [American Diabetes Association (ADA) and Japanese Diabetes Society] and ≤ 6.5% [American Association of Clinical Endocrinologists]) [3, 4, 5].
Glucagon-like peptide (GLP-1) is an incretin hormone that has a glucose-dependent stimulatory effect on insulin and an inhibitory effect on glucagon secretion from the pancreatic islets [6, 7]. The effects of GLP-1 are reduced in individuals with T2D [8, 9, 10, 11]; however, the ability of GLP-1 to lower blood glucose levels is preserved when it is administered at supraphysiologic levels [12]. GLP-1 also has effects on appetite and energy intake [13, 14] and is, therefore, an attractive pharmacologic option for the treatment of T2D [15, 16, 17]. The short terminal elimination half-life (t1/2) of endogenous GLP-1 (< 1.5 min after intravenous administration [18]) has required the development of GLP-1 receptor agonists with longer half-lives.
GLP-1 receptor agonists have become recognized treatment options for T2D [19], which stimulate insulin and decrease glucagon secretion in a glucose-dependent manner, thereby improving glycemic control with a relatively low risk of hypoglycemia [20].
Semaglutide (Novo Nordisk A/S, Denmark) is a subcutaneously administered GLP-1 analogue for the treatment of T2D. It has 94% amino acid sequence homology to native GLP-1, and is structurally similar to liraglutide, a once-daily GLP-1 receptor agonist [21]. Semaglutide's structural modifications from native GLP-1 make it less susceptible to degradation by dipeptidyl peptidase 4 (DPP-4) and, in addition, increase its specific high-affinity binding to albumin [21]. The resultant half-life of approximately 1 week makes semaglutide appropriate for once-weekly administration [22, 23].
The phase 3 global SUSTAIN trials were designed to cover a broad spectrum of the T2D patient care continuum, including drug-naïve patients as well as those on a background of orally administered antidiabetic drugs and/or insulin. In these trials, semaglutide was superior to all comparators in reducing HbA1c levels, providing clinically meaningful improvements in glycemic control and body weight reduction in subjects with T2D [24, 25, 26, 27, 28]. In SUSTAIN 6—a 2-year placebo-controlled trial investigating cardiovascular outcomes—semaglutide led to a significant 26.0% reduction in risk of the primary outcome (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) versus placebo [29].
Clinical pharmacology studies have shown that pharmacokinetic properties of semaglutide are not significantly affected by renal function [30] or hepatic impairment [31], suggesting that no dose adjustment is warranted. Similarly, no clinically relevant impact of semaglutide on concomitant orally administered medications was observed [22, 32].
Genetic differences, diet, and other environmental factors can contribute to differences in therapeutic drug response across different regional populations [33]. Therefore, the objectives of this clinical pharmacology trial were to compare the pharmacokinetics, pharmacodynamics, safety, and tolerability of semaglutide in healthy Japanese and Caucasian subjects using the same doses (0.5 and 1.0 mg) and dose-escalation regimen to reach steady state as in the semaglutide global phase 3 program.
Trial Design, Subjects, and Dosing
This was a clinical pharmacology, single-center, parallel-group, randomized, double-blind, placebo-controlled trial with two doses of semaglutide (0.5 mg and 1.0 mg) administered subcutaneously to healthy male Caucasian and Japanese subjects.
Healthy male subjects, age 20–55 years, with good glycemic control [HbA1c 6.0% (42 mmol/mol) or less]; body mass index (BMI) in the range of 20–25 kg/m2 with body weight of at least 54 kg; and with both parents either Japanese (for Japanese subjects) or Caucasian (for Caucasian subjects) were eligible for inclusion. Exclusion criteria included the presence or history of endocrine disorders and the existence of a first-degree relative with T2D, and were otherwise standard criteria for clinical pharmacology studies in healthy subjects.
Subjects were randomized within each ethnic group (Japanese and Caucasian) to receive either semaglutide 0.5 mg, semaglutide 1.0 mg, placebo 0.5 mg, or placebo 1.0 mg in an 8:8:3:3 ratio. Subjects were assigned to the lowest available randomization number on a subject-specific prepacked trial product (Clinical Supplies Coordination, Novo Nordisk A/S). Randomization to either active treatment or placebo was double-blinded, but assignment across doses was not blinded, because of differences in treatment volume.
Prior to initiation, the trial protocol and any amendments, the consent form, and the subject information sheet were reviewed and approved according to local regulations by appropriate health authorities, and by an institutional review board (IRB). The IRB for this study was Medical Co. LTA Hakata Clinic IRB, Japan. The trial was conducted in accordance with the Declaration of Helsinki [34] and the International Conference on Harmonization Good Clinical Practice guidelines [35]. Informed consent was obtained before any trial-related activities were initiated.
Trial Endpoints
The primary endpoint of the trial was area under the plasma semaglutide concentration–time curve during a dosing interval (0–168 h) at steady state (AUC0–168h,sema,SS). Secondary pharmacokinetic endpoints for semaglutide at steady state after the last dose of semaglutide, 0.5 mg or 1.0 mg, included maximum plasma concentration (Cmax,sema,SS), time to Cmax,sema,SS (tmax,sema,SS), total apparent clearance (CL/Fsema,SS), terminal elimination half-life (t1/2,sema,SS), and apparent volume of distribution (Vz/Fsema,SS). Secondary pharmacokinetic endpoints after the first dose of semaglutide (0.25 mg) were AUC0–168h,sema,SD, Cmax,sema,SD, and tmax,sema,SD. Other secondary pharmacokinetic endpoints included trough plasma concentration, 168 h after each dose of semaglutide 0.25 mg, 0.5 mg, and 1.0 mg (Ctrough,sema). The dose-corrected accumulation ratio (Racc,DC,sema) was calculated on the basis of AUC0–168h,sema,SD after the first dose and AUC0–168h,sema,SS after the last dose.
The pharmacodynamic endpoints were change from baseline to end of treatment—defined as 1 week after the last dose—in body weight, fasting plasma glucose (FPG), and other fasting glucose metabolism parameters (insulin, C-peptide, glucagon, and pro-insulin). Safety endpoints included incidence of adverse events, number of hypoglycemic episodes, incidence of anti-semaglutide antibodies at follow-up, and change in vital signs, electrocardiogram (ECG) readings, physical examination, and laboratory tests (hematology, biochemistry, calcitonin, and urinalysis).
Pharmacokinetic Assessments
Blood samples for pharmacokinetic assessment of semaglutide were taken before the first dose (0 h), for 1 week following a single 0.25 mg dose (6, 12, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 120, 144, 168 h), then weekly prior to the next dose (trough values), and for 5 weeks following the final dose (0 h then 6, 12, 18, 24, 30, 36, 42, 48, 60, 72, 84, 96, 120, 144, 168, 336, 504, 672 and 840 h).
Bioanalysis of blood samples was performed at a specialized laboratory (Celerion Switzerland AG; Fehraltorf, Switzerland), which used a validated liquid chromatography–mass spectrometry (LC–MS/MS) assay [22]. This assay measured the total semaglutide concentration and had a lower limit of quantification (LLOQ) of 0.7 nmol/L [22].
Pharmacodynamic Assessments
Body weight was measured at baseline (before first dosing) and at 8 and 12 weeks after first dosing and 1 week following the final dose. Subjects were weighed without shoes and wearing light clothing. Blood samples for assessment of glucose metabolism parameters (glucose, insulin, C-peptide, glucagon, and pro-insulin) were collected during fasting state: at baseline (before first dosing), 1 week after the fourth dose of 0.5 mg, and 1 week following the final dose. These parameters were analyzed using standardized procedures at a central laboratory (ICON Laboratory Services Inc., Dublin, Ireland) while Celerion Switzerland AG was responsible for the analysis of semaglutide and anti-semaglutide antibodies. Local laboratory facilities (Medical Co. LTA, Sumida Hospital; LSI Medscience Cooporation, and SRL Inc. [all Tokyo, Japan]) provided additional analyses including biochemistry, hematology, urinalysis, and other laboratory assessments.
Safety Assessments
Safety assessments included monitoring of adverse events/serious adverse event and vital signs, ECG, physical examination, hypoglycemic episodes, and laboratory testing (including presence of anti-semaglutide antibodies or hypersensitivity). All adverse events were coded using the Medical Dictionary for Regulatory Activities (MedDRA), version 17.1. Hypoglycemia was monitored at the trial site during the in-house visits by glucose measurement. Hypoglycemia was classified as severe according to ADA guidelines [36] or blood glucose-confirmed symptomatic hypoglycemia by a plasma glucose value of less than 56 mg/dL (3.1 mmol/L) with symptoms indicative of hypoglycemia.
Statistical Analysis
Sample size was not based on a formal statistical power calculation. A total of 44 subjects (22 Japanese and 22 Caucasian) were planned to be randomized to semaglutide 1.0 mg (n = 8), semaglutide 0.5 mg (n = 8), placebo 0.5 mg (n = 3), or placebo 1.0 mg (n = 3). In the analysis, the two placebo groups were pooled assuming no correlation between endpoints and placebo volume. A withdrawal rate of 15.0% was anticipated, which allowed for at least six steady-state pharmacokinetics profiles per dose and race group to be available for evaluation. All subjects who were randomized and exposed to at least one dose of trial product contributed to the pharmacokinetics, pharmacodynamics, and safety analyses.
The pharmacokinetic primary endpoint, AUC0–168h,sema,SS, was derived from the concentration–time curve during a dosing interval (0–168 h) at steady state using the linear trapezoidal method on the observed concentrations at actual time points. The AUC0–168h,sema,SS and other steady-state pharmacokinetic endpoints (Cmax,sema,SS and Racc,DC,sema) were analyzed separately by linear normal models based on log-transformed values with race (Japanese or Caucasian), dose group (0.5 mg or 1.0 mg), and race-by-dose group interaction as fixed factors. Estimated race differences (Japanese/Caucasian) by dose group and estimated dose-group differences (1.0 mg/0.5 mg) by race were transformed back to the original scale and presented as ratios with two-sided 95% confidence intervals (CI). A p value for the test of race-by-dose group interaction was also calculated. The race ratio for the pharmacokinetic endpoints (AUC0–168h,sema,SD and Cmax,sema,SD) after the first dose (0.25 mg) was estimated by linear normal models on log-transformed values.
For each pharmacodynamic assessment, treatment contrasts (semaglutide 0.5 mg and 1.0 mg versus placebo) at the end of treatment were estimated using a mixed model for repeated measurements using all post-baseline measurements up to the end of treatment. The model included visit, dose group, race, and race-by-dose interaction as fixed factors and baseline value as covariate. Furthermore, interaction terms of visit-by-dose group, visit-by-race, visit-by-race-by-dose group, and visit-by-baseline value were included. Fasting insulin, C-peptide, glucagon, and pro-insulin were logarithmically transformed.
Safety endpoints were summarized descriptively. We used SAS version 9.3 for all analyses.
Subject Disposition and Baseline Characteristics
Baseline characteristics of trial populations
Japanese subjects
Caucasian subjects
Semaglutide 0.5 mg
Semaglutide 1.0 mg
Semaglutide 0.5 mg
Semaglutide 1.0 mg
Mean [min.−max.]
Mean [min.−max.]
Mean [min.−max.]
Mean [min.−max.]
Mean [min.−max.]
Mean [min.−max.]
Age (years)
34.1 [23–44]
39.1 [29–47]
41.4 [27–51]
33.4 [26–52]
35.0 [25–51]
36.5 [26–49]
Height (m)
1.70 [1.62–1.81]
1.73 [1.65–1.86]
1.70 [1.65–1.75]
1.81 [1.74–1.90]
1.83 [1.72–1.95]
1.76 [1.71–1.81]
Body weight (kg)
63.9 [58.6–68.9]
64.3 [55.3–74.3]
62.4 [56.8–67.9]
74.9 [66.5–86.0]
73.5 [61.4–86.6]
69.8 [62.9–73.8]
BMI (kg/m2)
22.3 [20.0–24.7]
21.4 [20.1–24.5]
21.7 [20.4–23.6]
22.9 [21.2–24.9]
22.1 [20.0–24.5]
22.6 [20.0–24.5]
Pharmacokinetic endpoints at steady state
Japanese subjects
Caucasian subjects
Semaglutide 0.5 mg (n = 8)
Semaglutide 1.0 mg (n = 8)
Semaglutide 0.5 mg (n = 7)
Semaglutide 1.0 mg (n = 6)
AUC0–168h,sema,SS (nmol h/L)
3583 (17.8)
7449 (12.2)
3371 (2.4)
7490 (17.9)
Cmax,sema,SS (nmol/L)
25.1 (17.8)
51.6 (11.1)
23.7 (7.5)
50.6 (17.5)
tmax,sema,SS (h)†
30 [12; 72]
36 [18; 96]
36 [24; 72]
30 [24; 72]
CL/Fsema,SS (L/h)
0.034 (17.8)
0.033 (12.2)
0.036 (2.4)
0.032 (17.9)
t1/2,sema,SS (h)
145 (8.0)
163 (10.9)
159 (9.0)
167 (13.2)
Vz/Fsema,SS (L)
7.11 (12.8)
7.69 (14.0)
8.25 (11.1)
7.84 (19.6)
R acc,DC,sema
1.99 (10.2)
2.09 (6.8)
2.30 (10.2)
2.31 (9.5)
Statistical analyses of pharmacokinetic endpoints at steady state
Estimated treatment ratio [95% CI] (semaglutide 1.0 mg/semaglutide 0.5 mg)
Japanese subjects
Caucasian subjects
2.08 [1.80; 2.40]
2.22 [1.89; 2.60]
C max,sema,SS
2.06 [1.78; 2.38]
2.13 [1.82; 2.50]
R acc,DC,sema
1.05 [0.95; 1.15]
1.00 [0.90; 1.12]
Estimated race ratio [95% CI] (Japanese/Caucasian)
Semaglutide 0.5 mg
Semaglutide 1.0 mg
1.06 [0.92; 1.23]
0.99 [0.85; 1.16]
C max,sema,SS
1.06 [0.91; 1.23]
1.02 [0.87; 1.19]
R acc,DC,sema
0.87 [0.78; 0.96]
0.90 [0.82; 1.00]
The Cmax,sema,SS of semaglutide at steady state was also similar between Japanese and Caucasian subjects (Table 2), with estimated race ratios close to 1 and estimated treatment ratios close to 2 (Table 3). Other pharmacokinetic endpoints at steady state (tmax,sema,SS, CL/Fsema,SS) were comparable between the populations in both dose groups (Table 2). The elimination of semaglutide during follow-up, following the final dose, is shown in Supplementary Fig. S1. Although the Vz/Fsema,SS of semaglutide was similar between the populations and doses, the half-life of semaglutide (t1/2,sema,SS) appeared to be slightly lower in the 0.5 mg Japanese group versus the other dose groups (Table 2).
The exposure (AUC0–168h,sema,SD) and Cmax,sema,SD after a single dose (0.25 mg) of semaglutide was slightly higher in Japanese versus Caucasian subjects, as shown by estimated race ratios above 1 (Supplementary Table S1; Supplementary Fig. S2) and the tmax,sema,SD was earlier for Japanese subjects than for Caucasian subjects.
Trough plasma concentrations (Ctrough,sema concentration 1 week after the fourth dose of all dose levels) were similar between race groups and across doses, and trough levels were greater with the higher 1.0 mg dose upon dose escalation (Fig. 2). The dose-corrected accumulation ratio (Racc, DC,sema) was slightly lower in Japanese subjects than in Caucasian subjects (Table 3) but was comparable among dose groups (0.5 and 1.0 mg).
Mean body weight was decreased by 1.4 and 5.0 kg with semaglutide 0.5 and 1.0 mg, respectively, compared with an increase of 1.1 kg with placebo in Japanese subjects [estimated treatment difference versus placebo − 2.4 kg (p ≤ 0.05) and − 6.1 kg (p ≤ 0.05)]. In Caucasian subjects, mean body weight was reduced by 3.6 kg with semaglutide 0.5 mg and 7.5 kg with semaglutide 1.0 mg, versus an increase of 0.7 kg with placebo [estimated treatment difference − 4.3 kg (p ≤ 0.05) and − 8.3 kg (p ≤ 0.05)] (Supplementary Table S2).
No clinically significant changes in the different parameters of glucose metabolism from baseline to end of treatment were observed. There was a slight reduction in FPG in Japanese subjects receiving semaglutide 0.5 and 1.0 mg, compared with placebo and in Caucasian subjects receiving semaglutide 1.0 mg (Supplementary Table S2).
Overall, 32 subjects were exposed to semaglutide and 12 subjects to placebo across both populations. No deaths, serious adverse events, or adverse events leading to withdrawal were reported. The proportions of Japanese subjects reporting adverse events were 75.0% and 62.5% with semaglutide 0.5 and 1.0 mg, respectively, compared with 16.7% of subjects receiving placebo. In the Caucasian population, 50.0%, 62.5%, and 33.3% of subjects reported adverse events with semaglutide 0.5, 1.0 mg, and placebo, respectively (Supplementary Table S3). The number of events was higher in the semaglutide 1.0 mg group, compared with the 0.5 mg group (driven by three subjects having multiple events), with no apparent difference between the race groups. All adverse events were mild to moderate in severity; none were severe. Gastrointestinal adverse events were the most frequently reported events, and more common with semaglutide than placebo. A higher proportion of Japanese subjects reported gastrointestinal adverse events than Caucasian subjects: 62.5%, 37.5%, and 16.7% of Japanese subjects receiving semaglutide 0.5, 1.0 mg and placebo, respectively, versus 25.0%, 25.0% and 0.0% of Caucasian subjects, respectively (Supplementary Table S3). No hypoglycemic events were reported during the trial.
There was an elevation in pulse rate from baseline to end of treatment in subjects receiving semaglutide, with no apparent difference across the races and doses. Pulse rate increased by 8.5 beats per minute (bpm) and 10.4 bpm in Japanese subjects receiving semaglutide 0.5 and 1.0 mg, respectively, versus a decrease of 0.5 bpm with placebo. In Caucasian subjects, pulse rate increased by 14.6, 10.5, and 2.8 bpm with semaglutide 0.5, 1.0 mg, and placebo, respectively.
There were no clinically significant abnormalities in ECG readings or physical examinations. No noticeable trends were found in the biochemistry parameters, including amylase, lipase and calcitonin, in any of the treatment or race groups. No subjects developed anti-semaglutide antibodies as a consequence of semaglutide treatment.
This trial investigated whether the pharmacokinetics, pharmacodynamics, safety, and tolerability profile of semaglutide in healthy male Japanese subjects were similar to those in Caucasian subjects. The primary objective was to assess and compare exposure after multiple doses of semaglutide using the clinical therapeutic doses of 0.5 and 1.0 mg.
Semaglutide pharmacokinetic profiles and pharmacokinetic parameters were similar across both populations, and showed an expected higher exposure with the 1.0 mg dose, as demonstrated by the mean semaglutide concentration–time curves from first dosing to follow-up, which is supported by the statistical analyses. Furthermore, the pharmacokinetic properties of semaglutide reported in this clinical trial were comparable with those reported from other reported clinical pharmacology trials [22, 30, 31, 32].
Following multiple doses of semaglutide, the Cmax and tmax were found to be comparable between the races, despite a slightly higher mean semaglutide exposure and Cmax after the first single 0.25 mg semaglutide dose in Japanese subjects.
The dose-corrected accumulation ratio of approximately 2 was as expected on the basis of the half-life of semaglutide of approximately 1 week [21] and the once-weekly dosing frequency. Semaglutide 1.0 mg resulted in double the exposure of the 0.5 mg dose, with no difference between the two races.
Dose-dependent reductions in body weight were observed in all subjects receiving active treatment; however, this was more pronounced in Caucasian subjects, who had a higher mean body weight at baseline. Weight reduction is a known effect of GLP-1 receptor agonist therapies, and some, such as liraglutide, are licensed to treat individuals with obesity in some countries [37, 38]. Semaglutide was shown to provide significant and clinically meaningful improvements in glycemic control and body weight reduction in the global phase 3 trials versus all comparators [24, 25, 26, 27, 28], and in phase 3 trials of Japanese subjects with T2D versus sitagliptin and orally administered antidiabetic agent add-on therapy [39, 40]. As would be expected in a trial population of healthy volunteers, there were no clinically significant changes in glucose metabolism in the current trial.
No new safety and tolerability issues related to semaglutide were observed in this trial. There were no serious adverse events and no subjects withdrew because of adverse events, while three withdrew for personal reasons. Although semaglutide-treated Japanese subjects reported more gastrointestinal adverse events, the overall safety and tolerability profile of semaglutide was comparable between Japanese and Caucasian subjects and was similar to that reported in other semaglutide trials [24, 25, 26, 27, 28]. In line with results from other trials, gastrointestinal adverse events—an established side effect of GLP-1 receptor agonist therapy [41]—were reported more frequently with semaglutide.
In this trial of healthy volunteers, there was an elevation in pulse rate in semaglutide-treated subjects; however, considering the low sample size, the change observed in Japanese and Caucasian subjects was comparable. Only minor increases in pulse rate from baseline were observed across the phase 3 SUSTAIN program in subjects with T2D [24, 25, 26, 27, 28]. In SUSTAIN 6, the largest trial investigating semaglutide, with the longest duration reported to date in subjects with high cardiovascular risk, mean pulse rate increases of 2.1 and 2.4 bpm were reported with semaglutide 0.5 and 1.0 mg, respectively, versus no change with placebo. Despite this slight elevation, it should be noted that semaglutide-treated patients had a 26.0% lower risk of the primary composite outcome (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) than those who received placebo [29].
GLP-1 receptor agonists are known to affect pulse rate [42] and, accordingly, when semaglutide was compared head-to-head with another once-weekly GLP-1 receptor agonist, exenatide extended release, the elevation in pulse rate was not significantly different [26]. There were no cases of positive anti-semaglutide antibodies or episodes of hypoglycemia reported during this trial.
This trial had a relatively short duration and a small sample size. Furthermore, the subjects enrolled were healthy, lean individuals with no expected effects on pharmacodynamic parameters. A key limitation of the study is that participants were not entirely representative of the population for which semaglutide treatment is intended, in individuals with T2D. It has been proposed that the pathophysiology of T2D in Japanese patients is primarily characterized by β-cell dysfunction, while obesity and insulin resistance are believed to be the key drivers of T2D in Caucasians [43]. As semaglutide improves β-cell function and corrects insulin secretion [44], these actions may be highly beneficial to Japanese patients [45]. The efficacy and safety of semaglutide in Japanese patients with T2D have previously been reported in larger, phase 3 trials [39, 40]. These investigations showed that the responses were similar in the two populations. It may be of clinical interest to understand if there are any differences in mechanism of action across these different populations in regards to improving glycemic control.
In summary, while this study reached its objective and enabled the analysis of pharmacokinetics and safety across healthy Japanese and Caucasian subjects, future studies may investigate the differences in pharmacokinetics and pharmacodynamics across Japanese and Caucasian patients with T2D.
Following multiple doses of semaglutide 0.5 and 1.0 mg, exposure of semaglutide at steady state was comparable between Japanese and Caucasian subjects, with an expected dose-dependent increase. The safety findings were comparable across the populations. These findings suggest that no dose adjustment would be required for the clinical use of semaglutide in Japanese subjects.
Sponsorship for this study, article processing charges, and the open access fee were funded by Novo Nordisk, A/S.
Editorial Assistance
We also thank Gurudutt Nayak (Novo Nordisk A/S, Denmark) for his review and input to the manuscript, and Nicole Antonio, PhD (AXON Communications, UK) for medical writing and editorial assistance. Support for this assistance was funded by Novo Nordisk.
All of the named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published. All authors had full access to all of the data in this study and take full responsibility for the integrity of the data and accuracy of the data analysis.
We thank all the participants, investigators, and trial-site staff from Medical Co. LTA, Sumida Hospital in Tokyo, Japan who were involved in the conduct of the trial.
Shin Irie's institution has received funding to conduct clinical trials from Novo Nordisk, Eli Lilly and Company, Teijin Pharma, Daiichi Sankyo Company, Takeda Pharmaceutical Company Limited, Sanofi K.K., Nippon Boehringer Ingelheim Co., and AstraZeneca. Ippei Ikushima's institution has also received funding to conduct clinical trials from Novo Nordisk, Eli Lilly and Company, Teijin Pharma, Daiichi Sankyo Company, Takeda Pharmaceutical Company Limited, Sanofi K.K., Nippon Boehringer Ingelheim Co., and AstraZeneca. Lene Jensen is an employee and shareholder of Novo Nordisk A/S. Anne Flint is an employee and shareholder of Novo Nordisk A/S. Jeppe Zacho is an employee and shareholder of Novo Nordisk A/S. Tomoyuki Nishida is an employee of Novo Nordisk Pharma Ltd. and shareholder of Novo Nordisk A/S.
Compliance with Ethics Guidelines
Prior to initiation, the trial protocol and any amendments, the consent form, and the subject information sheet were reviewed and approved according to local regulations by appropriate health authorities, and by an institutional review board (IRB). The IRB for this study was Medical Co. LTA Hakata Clinic IRB, Japan.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments and the International Conference on Harmonization Good Clinical Practice guidelines. Informed consent was obtained from all individual participants included in the study.
Data Availability
The datasets generated and/or analyzed during the current study are not publicly available as this was a phase I study, but are available from the corresponding author on reasonable request.
Open Access
This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Supplementary material
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- 28.Rodbard H, Lingvay I, Reed J, et al. Efficacy and safety of semaglutide once-weekly vs placebo as add-on to basal insulin alone or in combination with metformin in subjects with type 2 diabetes (SUSTAIN 5). Diabetologia. 2016;59(Suppl 1):S364–5.Google Scholar
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- 35.International Conference on Harmonisation Working Group. ICH harmonised tripartite guideline: guideline for good clinical practice E6 (R1). 1996. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E_R1_Guideline.pdf. Accessed Oct 2016.
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School Students & Faculty
Pattison School circa 1907
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The teacher is Beulah White, seated in center front. Eddie Gus Neuman Sr. is the fifth boy seated from the left with hat. Ora Halbison Neiman (not Neuman) is kneeling to the left of the teacher. Ethel Clark is the fair-haired girl at teacher?s left shoulder. The Baronian girls are in the top row in matching dark dresses. This Pattison School was located on the present school grounds across from the old Baker house. Photo from the collection of Marie Neuman Gottfried.


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Name: Where does zinio reader 4 store s
File size: 74mb
Language: English
Rating: 6/10
A: The Zinio Alert Messenger runs alongside the Zinio Reader 4 and, when you' re online, will notify you when a new must logout of the Reader before closing to save preferences). You can do so by clicking here. For a Mac, they are stored in a folder. To bookmark (or mark a page as a favorite) in the Zinio Reader 4: Open the comments and tags for the bookmark; Click Save to store the bookmark you have experience is to use our apps within iPad or Android or the online reader at.
All publications which have been downloaded can be read offline. To download a publication in the Zinio Reader 4: Ensure you are in. Hello, I am using zinio service. feelfreshmedia.com The reader is installed in /opt /Zinio Reader 4 What is the directory where the publications. Part 3) How to download and use Zinio Reader 4. .. to select, store and access your library magazines; building your own unique collection. to locate your checked out magazine(s). 4. You can now view your magazines online or download.
Part 3) How to download Zinio Reader 4. . 4. A second browser window will open to feelfreshmedia.com "Pick up your digital subscription to " to select, store and access your library magazines; building your own unique collection. (in some cases, where magazine publishers have allowed this) and zoom the page(s) to enjoy. 5) Do I need to be online to checkout magazines in Zinio for Libraries? . .. 6. 6) Do I need to be online to read . 1) What is the feelfreshmedia.com Personal Reading Account? secure server that stores all the issues. If you download a . ZINIO is the world's first and largest digital newsstand, giving you access to magazine content .. Enhanced text mode for optimal reading on mobile devices. 9 Jul When I walk into my local book stores I sometimes cringe when I see the number of magazines As it stands now, Zinio Magazine & Reader (iTunes Store link) is the most useful digital magazine publication app for the iPad. Has anyone figured out where Zinio stores our MR's on our local computers? The other day I was reading some MR's in the Zinio Reader and started This is there the actual odf files for each issue of MR in the 75 year.
Part 3) How to download Zinio Reader 4 Scroll through the pages clicking " Next" or the page numbers at the top and 4. A second browser window will open to feelfreshmedia.com "Pick up your digital . Type "zinio" into your App Store and install: 1. ZINIO is the world's first and largest digital newsstand, giving you access to magazine content from the best publishers across the globe. For over a decade, Zinio. Thank you for your interest in our Zinio for Libraries Collection. Our publications are always You will only need to download the Reader 4 software once. You may your Zinio account page or from the Apple Store (iPhone, iPad, Mac) or Play Store (Android). most cases) and zoom the page(s) to enjoy more page detail. Is there an app magazine quantity limit for my feelfreshmedia.com Personal Account collection? How do I How do I access my library's magazine collection from the Zinio Reader 4 app to checkout .. global secure server that stores all the issues.
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AAA: Shoppers Plan to Spend More this Holiday Season
Broadcast Quality Sound Bites (
View and Download
AURORA, Ill.
(November 24, 2017) — Nearly one in four shoppers in Illinois (23%) say they will spend more on gifts in 2017, according to a recent
AAA Consumer Pulse survey
. The boost in spending comes from a strong labor market, which is generating higher incomes and boosting consumer confidence. Overall, AAA has seen a 40% increase in shoppers who say they will spend more money on gifts this holiday season.
When Will They Shop?
November is the busiest time of year for holiday shopping, according to AAA research. The majority (80%) of consumers will begin their holiday shopping before December. The top shopping days for consumers are all in November: Black Friday (52%), Cyber Monday (51%), and Thanksgiving Day (20%). The average Illinois shopper plans to spend $956 on gifts this holiday season.
"According to our research, Black Friday and Cyber Monday are expected to be the busiest shopping days," said Beth Mosher, director of public affairs for AAA - The Auto Club Group. "Gift cards and apparel will be at the top of most lists this holiday season."
Gifts Consumers Want Under the Tree
Gift Cards (27%)
Cash (23%)
Clothing (11%)
Travel (9%)
Electronics (7%)
Gift cards, cash, and clothing are the top gifts people want this holiday season. The top selling gift cards are Amazon, Home Depot, and Lowes, according to AAA.
"Gift cards can take some of the stress out of holiday shopping," said Mosher. "Purchasing a gift card allows the recipient to purchase items they enjoy and the savvy shopper can also enjoy some benefits as well. Many companies, including AAA, have some great perks for gift card buyers this holiday season.
Those who purchase gift cards online at the
AAA Gift Card Center
can earn 2 percent in AAA Dollars
, plus receive free digital personalization.
More Consumers Will Use Their Phones to Shop
More than one in three (36%) will use their smart phone to purchase gifts this year, a 16% increase over 2016.
Online shopping
continues to gain ground this holiday season as 74% of shoppers say they will do at least half of their shopping on the web.
Cyber Monday
will be the second busiest shopping day of the year behind Black Friday. More than half (53%) of shoppers plan to buy gifts on the Monday after Thanksgiving, and retailers are responding. Holiday vendors, hungry for a piece of the online shopping share, are advertising on social media, and optimizing their websites and apps for mobile phones and tablets.
"Shoppers are increasingly drawn to the convenience of online shopping," continued Mosher. "Shopping online allows people to avoid the crowds and shop at their convenience. AAA members can find even deeper discounts and rewards opportunities by going to the AAA Dollars Online Mall at
or using the new AAA Mobile app."
How to Save on Holiday Shopping
Utilize Discounts
– Search for retailer coupons or join mailing e-mail lists for exclusive discounts. Savvy shoppers looking for a bargain this holiday season can utilize the benefits of membership organizations like AAA. AAA members receive instant discounts at many retail locations including Reebok Outlet Stores, LensCrafters®, and Sprint. AAA members can also earn
AAA Dollars
® online, on top of any online offers, at over 80 name-brand partners, including Walmart.com, iTunes, Target.com, Kohl's, QVC, and Macy's through AAA.com. Earned AAA Dollars® are like reward points which can be used to lower the renewal price of your AAA membership.
Shop Online
– Shoppers can easily compare retailers online and find the best price for the products they want to purchase. Many retailers also offer exclusive online discounts and coupons through their app or website. Shoppers can download the new AAA Mobile app to find retailers that offer additional discounts for AAA members in their area. Just visit
to download
Shop your budget
– Set a spending limit before you start your gift purchasing. Nearly half of consumers (47%) will use a credit card for purchases this year. If using a credit card, use one that offers rewards that can help defray the cost of gift giving. Credit cards such as the AAA Dollars Plus® Mastercard® offer 3% AAA dollars on AAA and travel purchases; 2% on grocery, gas, and drug store purchases; and 1% on other everyday purchases.
About the AAA Consumer Pulse™ Survey
The AAA Consumer Pulse™ Survey
was conducted online among residents living in The Auto Club Group territory from October 10, 2017 – October 18, 2017. A total of 4,011 residents completed the survey, with 3,646 planning to purchase gifts during the 2017 holiday season. Overall results have a maximum margin of error of ± 1.6 percentage points. Illinois results have a maximum margin of error of ± 5.2 percentage points. Responses are weighted by gender and age within state to ensure reliable and accurate representation of the adult population (18+).
About The Auto Club Group
The Auto Club Group (ACG) is the second largest AAA club in North America. ACG and its affiliates provide membership, insurance, financial services and travel offerings to over 9.4 million members across eleven states and two U.S. territories including Florida, Georgia, Iowa, Michigan, Nebraska, North Dakota, Tennessee, Wisconsin, Puerto Rico and the U.S. Virgin Islands; most of Illinois and Minnesota; and a portion of Indiana. ACG belongs to the national AAA federation with more than 57.7 million members in the United States and Canada and whose mission includes protecting and advancing freedom of mobility and improving traffic safety. Motorists can map a route, identify gas prices, find discounts, book a hotel, and access AAA roadside assistance with the AAA Mobile app for iPhone, iPad and Android. Learn more at
. AAA clubs can be visited on the Internet at
AAA Dollars
is a free loyalty program where members can earn
AAA Dollars
on transactions through AAA and participating partners. The
AAA Dollars
you earn will be applied toward your next membership renewal. To learn more go to
The creditor and issuer of the AAA Dollars Plus® Mastercard card is U.S. Bank NA dba ACG Card Services, pursuant to a license from Mastercard International Incorporated. Mastercard is a registered trademark, and the circles design is a trademark of Mastercard International Incorporated. © 2017 ACG Card Services. All rights reserved. Equal Credit Opportunity Lender.


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Thursdays, 4:00-5:00 pm
1-434 Physics and Astronomy (map)
Reception from 3:30-4:00 p.m.
(unless otherwise posted)
Guest Speaker: Cristiano Galbiati (Princeton University)
Talk Title: "The DarkSide Program for Direct Dark Matter Searches at LNGS"
The DarkSide-50 dark matter detector is a two-phase argon TPC installed at Laboratori Nazionali del Gran Sasso at the center of two nested veto detectors, a 30-tonne liquid scintillator neutron veto and a 1,000-tonne water Cherenkov muon veto. While operating in 2014 with a fill of argon extracted from the atmosphere, DarkSide-50 demonstrated its capability to operate in a background-free mode even in presence of the strong radioactive background due to the 39Ar isotope produced by cosmic rays. Today DarkSide-50 is the only noble liquid dark matter detector operating in background-free mode. In 2015 DarkSide was filled with 150 kg of argon extracted from deep underground reservoirs, which was demonstrated to be highly depleted in 39Ar. The combination of these two successes allows to project that DarkSide-20k, a 20-tonne depleted argon detector just proposed for installation at LNGS, will be able to operate completely free of background. The DarkSide-20k detector is set to start operating by 2019 and is projected to be the most sensitive dark matter experiment to start data taking by 2020, with a sensitivity reaching well past the ultimate value possible for xenon-based detectors and close to the ultimate background due to nuclear recoils induced by neutrino cohere scattering.
DarkSide-20k will be followed after five years at LNGS by Argo, a 300-tonne dark matter detector also capable of performing a set of very high precision measurement of several solar neutrino sources.
Both programs are made possible by significant investments by MIUR and INFN in the procurement of underground argon (Urania Project) and in its additional isotopic rejection of 39Ar (Aria Project).
For more information, contact Jay Hauser
We thank the following people for their contributions to the wine fund for the post-colloquium reception:
Prof. Dolores Bozovic, Prof. Mike Cornwall, Prof. Bob Cousins, Prof. Andrea Ghez, Prof. Karoly Holczer, Prof. Eric Hudson, Robert Huff, Prof. Alex Kusenko, Prof. Myank Mehta, Prof. John Miao, Prof. Roberto Peccei, Prof. Claudio Pellegrini, Prof. David Saltzberg, Prof. Jean Turner and Prof. Ben Zuckerman.
Copyright © 2018 by UCLA Physics & Astronomy, 475 Portola Plaza, Los Angeles, CA 90095-1547, (310) 825-3440. Template by OS Templates | Sitemap


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NCM Motorsports Park Calendar of Events
Events for September 8, 2018 › Karting
Events Search and Views Navigation
9:00 am
Junior Kart Clinic
Is your child interested in go-karts, but they don't have a lot of experience driving or not sure where to start? The new Junior Kart Clinic is designed to teach kids the fundamentals of karting combining both curriculum and behind-the-wheel practice. 8 spots available. $50 per child and includes all equipment. We will keep class […]Find out more »
10:00 am
Go-Karts Open to Public
Arrive and drive for a fun racing session against your friends on the new go-kart track! Karts and safety equipment provided. Hours of Operation: Monday CLOSED Tuesday 12:00PM-7:00PM Wednesday 12:00PM-7:00PM Thursday 12:00PM-7:00PM Friday 12:00PM-7:00PM Saturday 10:00AM-7:00PM Sunday 12:00PM-7:00PM *Hours are subject to change due to inclement weather. Interested in a private party? Check out details here. […]Find out more »


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GE's Next CEO to Get $5 Million in Target Pay but No Special Stock Award
John Flannery to receive $2 million salary; finance chief Jeff Bornstein granted some $7.2 million in restricted stock
General Electric Co.'s leadership reshuffle left the company's new chief with target annual pay of $5 million and a runner-up for the job with a shot at more than $7 million in GE shares if he sticks around for five years.
John Flannery, who on Monday was named GE's chief executive effective Aug. 1, will receive salary of $2 million and a target bonus of $3 million a year, according to a securities filing. Any long-term incentive paid to Mr. Flannery for company performance through 2018 will be made in stock....


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A critical analysis (sometimes called a critique, critical summary, or book review) is a systematic analysis of an idea, text, or piece of. Whenever it gets a critical airing at all, essays and fiction on the craft of writing, as bright lights film journal points out,. Essays on film noir film noir studios features some great reading by essayist john blaser this site offers numerous, insightful pieces and is a great resource for. Download and read america rediscovered critical essays on literature and film of the vietnam war america rediscovered critical essays on literature.
Best help on how to write an analysis essay: critical essays are very popular among college students, although not all of them like these essay types. Download and read film genre 2000 new critical essays the suny series cultural studies in cinema video film genre 2000 new critical essays the suny series. The critical thinking goal: i might find that some of the essays were drawn out too long, what are his reasons to support his overall judgment of each film. Writing a critical essay about literature the idea behind critical analysis of literature is to write an infinite number of essays might randomly hit upon mla.
Application essays how to review a play several critical or problematic points within the play that may be of particular interest to watch for in the. Critical analysis template in a critical analysis essay, you systematically evaluate a work's effectiveness including what it does well and article or film. Encuentra shakespeare on film: contemporary critical essays (new casebooks) de robert shaughnessy (isbn: 9780333720172) en amazon envíos gratis a partir de 19. Formatting your critical essay title: an essay is an examination of a single topic because critical essays must back each point with solid evidence, it's much easier. 'the others' is a film written and directed by movie analysis of the others film film studies essay writing service essays more film studies essays.Free critical analysis papers, essays, and research papers. » literature and literary criticism movies and film music philosophy psychology essays, broadsides and more critical schools and movements,. We are glad to introduce you our database of free critical essay samples these critical essay examples are to help you understanding how to write this type of essays. Arrow is a american television series which can be classified in the action adventure genre the central character is oliver queen a playboy billionaire who was lost. In an essay, and even in longer essays like 4,000 word essays, examples, theories, other people's writing - question it, adopt a critical standpoint,. Download and read film genre 2000 new critical essays film genre 2000 new critical essays introducing a new hobby for other people may. Higher english critical essays: getting i got 19 and 20 for my two critical essays that i just completed i love the novel and the film but just doing a. Scholarly or focused critical writing about particular films--both current and historical--can be found in an amazingly wide variety of sources, including film.
Rereading: three decades after she first read the go-between as a teenager, ali smith finds that lp hartley's masterpiece can also be read as a sophisticated gay novel. Examples of film studies essays content by carter staub and savannah gillespie, site by megan venable a look at a real paper: here are two examples of analytical papers. Retrieved from topics and well written essays.
While watching your film: a strong film analysis will include a lot of be prepared to stop the film at critical segments so that you can jot down. The telegram iain crichton smith's short story the telegram tells of the escalating fear of two women, related as and a level war poetry essays. ¾ two types of lens essays: your expectations for the lens essay from a gratuitous sequence of crass jokes into a film using at least one of our critical.
She also suggests that while critical essays have more brain than the heart, jean-luc godard describes his recent work as film-essays. Critical reading: identify the author remember that the purpose of a critical analysis is not merely to inform, but also to evaluate the worth, utility. The help- a critical review there is the narrative itself, both as book and film there is the personal narrative of the author, kathryn stockett,.Download
2018. Term Papers.


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Northern Arizona University
I'm pursuing a degree in Computer Science with an eye toward continuing with Graduate work and possibly teaching. In any event, here are some links relating to my work there:
- Media:Hiragana_keyboard_layout.doc - A keyboard layout for MS Windows Input Method
- Media:Composition_Form1.doc - A printable Composition Form for Japanese essays
- Media:Japanese_101_Notes.doc - Japanese 101 Grammar Notes
- Media:Japanese_101_Vocabulary.doc - Japanese 101 Vocabulary List
CS 499 - Virtual Worlds
Quick example projects listed below. Just unzip into a directory and run the project executable. You may enjoy the images and sounds in the /res directory. Starting with project 2 there is a resource.txt file for configurable params and replacement of sounds and images. Sorry, no code but feel free to email questions.
- Project 1 - PlasmaCore API test.
- Project 2 - Simple Battleship game, no AI. State Machine example.
- Project 3 - 3D Pong. No real challenge but fun to play with the parameters.
- Project 4 - Procedural Animation music video
- Project 5 was a virtual robot on an arena server. Since the server is proprietary to the instructor, the code is basically useless for upload.
- Project 6 - Demo using tiles to build a roadway. Hypnotic. I should add a subliminal message...
- Project 7 - Extension of the last project to add procedural graphics. Still no game.
- Project 8 - AI project; this one solves those peg puzzles from Cracker Barrel.
- Final Project - 'Turbo Gauntlet': a maze-running, puzzle-solving game. You can make your own levels...
CS 499 - Virtual Worlds 2
This sequel to the popular class leads us into game production. While one team builds an actual arcade cabinet with controls and even a working coin slot, another implements a menu system to allow multiple student-created games to be showcased on the system. That leaves the rest of the students to produce games to run on the system.
- ZAP (Asteroids) - An Asteroids clone for the game cabinet
- ZAP Duel (SpaceWars) - A SpaceWars clone for the game cabinet
CS 486C - Capstone
This "class" is the Senior Design Project that must be completed before receiving a degree from NAU. I am Team Leader for Team Celestial, whose project is to develop a target scheduler for the Discovery Channel Telescope here in Arizona, working with Lowell Observatory.
- Team Celestial - Capstone Web Site


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"Since I can remember, my eyes have always grown big at
tales of the marvelous."
- L. Frank Baum
- Who's the girl behind the book?Or learn about the book...
Top Posts & Pages
Archives (since Nov, 2010)
Recommended BlogsBook BloggersMegwritesAuthors
More to come as I find them. Have a favorite? Tell me!
Share the love of reading with others...all around the world.
Category Archives: Historical Fiction
Book and TV Review: Father Brown
I've been watching the TV series Father Brown (a BBC series, available on Netflix) for many months now, and it's quite delightful. I thought I'd try the original stories, written by G. K. Chesterton, and got The Innocence of Father … Continue reading
Posted in Historical Fiction, Reviews Tagged Books 1 Comment
Book Review: The Go-Between
Based on anecdotal evidence, you likely have never heard of The Go-Between by L.P. Hartley, but you might know its opening line: "The past is a foreign country. They do things differently there." I picked the book up recently because … Continue reading
Posted in Historical Fiction, Reviews Tagged Books, Michael Crawford 2 Comments
Book Reviews: Good Masters, Sweet Ladies and Crispin
I accidentally paired two Newberys lately, and found myself reading two books about small medieval villages in a row. Which actually worked out well, as a lot of historical elements paralleled and supported each other. First I read Good Masters, … Continue reading
Posted in Historical Fiction, Reviews Tagged Books Leave a comment
Book Review: Kira-Kira
Continuing the pattern of last year, I'm making a good run through the Newbery winners. I picked Kira-Kira by Cynthia Kadohata in part because it also serves my diversity challenge, centering on a Japanese-American family living in Georgia in the … Continue reading
Posted in Historical Fiction, Reviews, Young Adult Tagged Books 1 Comment
Book Review: Mansfield Park
I recently reread (via audiobook) Mansfield Park by Jane Austen, one of my favorite Austen novels–although it rather surprises me that it is a favorite! As sometimes happens, rereading gave me a few more insights. Our heroine is Fanny Price, … Continue reading
Posted in Historical Fiction, Reviews Tagged Books 1 Comment


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In a recent post I looked at the role that parenting plays in the onset of Borderline Personality Disorder (BPD). I wanted to draw attention away from what most people who don't live with this illness experience – the behaviours – and look at the causes, because hopefully if we understand the causes we can … Continue reading Mental Illness: Born with Imperfection, Living with Compassion
Month: October 2017
ME: Working with a Neuropsychologist
I've recently been given a new member to the ever-growing team who care for my mental and physical health needs, one that I didn't even know existed until a few months ago. Her name is Nita. Nita is a neuropsychologist. Probably like me you have no idea what a neuropsychologist does or how they can … Continue reading ME: Working with a Neuropsychologist
Mental Illness: The Bruising Effect of the Dysfunctional Childhood
In my next couple of posts, I'm going to share in simple terms what I've learned about the two major contributors to emotional illness – a dysfunctional family life during childhood and natural temperament. I hope that by spending a few minutes reading this you will be able to get a better understanding of how … Continue reading Mental Illness: The Bruising Effect of the Dysfunctional Childhood


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by Ed Cherry
(from Jersey Coast Anglers Association October 2002 Newsletter)
On the Matter of Amendment 4, Interstate Weakfish Management, hearings are going to be held October 7, 2002, 6:00 P.M., Vineland Public Library, Doris Tripp Room, 1058 E. Landis Avenue, Vineland, N.J. and October 16, 2002, 7:00 P.MN., Ocean County Administration Building, 101 Hooper Avenue, Toms River, N.J.
It is important that you get, read and comment on this plan. The way the plan currently reads, New Jersey and Delaware take the BIGGEST HIT. The best-case scenario for New Jersey is a 65% reduction in recreational catch and the worst-case scenario is a 76% hit. The plan is a disaster. This is an open-ended fishery, with no quotas either on the commercial or recreational sides. However, the recreational anglers of New Jersey and Delaware are being asked to subsidize the rest or the other states' recreational and commercial fisheries by being hit with more restrictions. New Jersey has been arbitrarily removed from its historical position in the southern management zone and placed in the northern zone. This on a stock the amendment admits is in a good state and rebuilding rapidly. A weakfish stock assessment [Stock Assessment Workshop (NMFS 2000)] indicated that weakfish were "at a high level of abundance and subject to low fishing mortality rates." It is really not doing much on the commercial sector, which harvests 70% of the catch, except proposing the relaxing of some commercial regulations. With only a modest increase in market price of fish the commercial fishery could triple overnight. What is even stranger is that it is other recreational anglers in other states that are the drivers behind this amendment and their state directors, seeing this as a way to allow an increase in their commercial fishery, are more than happily respecting their request. This is the same scenario that is taking place in the Striped Bass fishery which proposes reducing the mortality rate and allowing for an increase in commercial catch. What is even worse is that the weakfish amendment is proposing a north-south line that has no scientific basis. We must tell our ASMFC Commissioners and Governors from New Jersey and Delaware that they cannot allow this to happen and if it does to sue the ASMFC for being discriminatory.
Interested parties should obtain a copy of the draft as outlined below.Written comment will be accepted until October 31, and should be submitted to:Carrie SelbergWeakfish FMP Coordinator 1444 Eye Street, NW Washington, DC, 20005 (202) 289-6051 (fax) or firstname.lastname@example.com. For more information, please contact Carrie Selberg, at (202) 289-6400.Write or call for a copy of the draft amendment 4, or download the .PDF format document from http://www.asmfc.org.


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