text:
Does survival hinge on innovation?
For the second time in 20 years, America is clawing its way out of an economic disaster.
While it’s still too early to pop any bottles of champagne and declare that the worst is behind us, there does seem to be economic light at the end of this seemingly endless COVID-19 tunnel. Work hours are on the rise for small businesses across the country, restaurant reservation numbers continue to climb, and investors are getting bolder as the stock market rebounds.
Still, all this seemingly good news is a bitter pill to swallow for the thousands upon thousands of small businesses (and large ones) that have shut down for good. Including many in the logistics and transport industry.
But what determines which businesses live or die? How have businesses who survived changed? And how can those of us in logistics improve our odds in the next economic disaster?
COVID-19 Survival Hinges on Tech
Survival for individual businesses looks very different depending on their size and flexibility. While it hasn’t been easy, there are plenty of small businesses who’ve managed to stay afloat despite the odds. The same can be said about retail giants, some of which have thrived despite adversity. Or even because of it. Here are the trends we’ve noticed in those who’ve made it this far.
For small business, local trucking companies, and small freight brokerages
For small businesses, the name of the game is efficiency and quick pivots. We’ve seen it in the consumer sector over and over as trendy bars rush to offer take home cocktail kits and celebrities flock to Cameo. But for those of us in logistics, “quick pivots” look very different than simply hosting virtual happy hours. Trucking companies who feel the squeeze can’t easily turn their dry vans into ice cream trucks, and logistics coordinators can’t magic more freight into the market.
However, while volumes cratered in some sectors – primarily manufacturing – they also spiked in others. The businesses who were able to survive were those who were already servicing “the right kind” or freight or could quickly move into a different vertical and make up the difference.
And one common thread of businesses who could quickly respond to the market shifts? Technology.
Small businesses and technology
Technology has helped businesses thrive through COVID-19 and may well be a deciding factor for those who’ve kept their doors open through the pandemic. It makes intuitive sense. Technology is fast. It’s efficient. If a business was already built to operate as quickly as possible, it’s easy to make and adapt to quick decisions. Even dramatic ones.
Owner operators who use virtual load boards are better equipped to quickly snatch up volume. Midsized carriers who’ve already virtually registered with digital brokers or freight networks can get loads in real time instead of waiting in line to be onboarded.
Meanwhile, shippers who rely on capacity that is suddenly under crunch need to prevent costly disruptions and delays. A feat that’s far easier if your provider has a digital portal that provides instant pricing and 24/7 access to capacity.
For large corporations, national 3PLs, and major trucking companies
For large entities, a “quick pivot” is much easier said than done. Nothing is fast when you have thousands of employees and potentially hundreds of offices. Even less so if you’re desperately trying to close those offices and move those employees online.
Being scrappy is much harder with the kind of overhead that comes with a big name, so the game is all about being proactive.
COVID-19’s biggest winners (ecommerce, telework providers) were already well positioned for the new normal, while the biggest losers (hotels, restaurants) were firmly at its mercy. For either end of the spectrum there isn’t much to be done, but for those in the middle looking to weather the storm it all comes down to efficiency.
That “overhead” problem we mentioned before equates to a lot of monthly expenses once covered by profits. If a company’s pockets aren’t deep enough to eat the costs, that means cutting those costs. A process that is especially painful if the company had been augmenting innovation and efficiency with additional workers.
But there’s only so much austerity measures can do, which means those companies who were already efficient were in a much better position to avoid layoffs, losses, and stoppages when their workforces were made to go remote.
The key to efficiency? Technology. Again.
Large corporations and technology
Offices that were already remote or partially remote were extremely well positioned for the lockdown, and managed to avoid the cost of vacating offices, providing additional equipment, or spending hours training staff on telework best practices. Businesses that had already switched from phone calls to organized internal communication tools improved their intercompany communications and potentially saved millions of dollars a year.
Those truisms similarly apply to major shippers. Streamlining pricing and booking saves time, and when your workforce is thousands strong, time is money. Not relying on confusing email chains and unrecorded phone calls cuts down on costly communication errors. And working with logistics providers who are already tech-enabled and highly efficient means cost savings get passed right back to shippers. It also ensures that big disasters don’t interrupt the supply chains that are vital to profits.
The New Freight Tech Normal
All this boils down to a lot of businesses either predisposed, or forced to be disposed, to using technology to improve their business. What does that mean for logistics moving forward?
It means an increase in automation and digitalization across multiple facets of the global supply chain. In fact, a post COVID-19 survey of over 300 shipping and freight professionals revealed that a whopping 67.6% of them plan to invest in technology. This could mean a serious overhaul in the industry that will send ripples across the globe. There is a major push in logistics to go digital to be better prepared for big disasters, but also to improve business in the interim.
Experts are already extolling the virtues of automation and warning that those in logistics who don’t invest in technology are “going to go under.”
Even freight tech itself is evolving. Automation and AI have both been cited as key for traditional brokers and digital brokers alike in the coming years. SaaS solutions may well be key to giving mom and pop logistics shops a competitive edge against industry titans. Visibility in particular continues to be one of the most important aspects of the freight tech revolution. So much so that a Gartner study on the logistics response to COVID-19 revealed that by 2023, 50% of global leading enterprises will have invested in real-time transportation visibility solutions. It makes sense, you can’t respond quickly unless you know you need to respond.
Long story short: logistics technology adoption has gotten a huge boost, which will mean faster supply chain management, and better shipment visibility.
Preparing for the worst
Unfortunately, there is always another disaster on the horizon.
The next hurdle could be natural or economic, and it could spell doom for many more businesses. It’s impossible to be fully prepared for every possible scenario (alien invasion, anyone?) but it is possible to take precautionary measures and learn from the past. COVID-19 is driving unparalleled tech adoption across the board, and it’s largely fueled by a fundamental truth of nature and business.
We must adapt, or our businesses will die.

domain: finance


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"Please don't consider Galactic as just another 'jam band,'" a Capricorn Records publicist requests in a letter that announces the April 4 arrival of the New Orleans sextet's "Late For the Future" album. The disc (the group's third) is another deeply grooving affair, with saxophones, keyboards and guitars slicing slinky riffs through the sticky, Crescent City rhythms pumped out by mighty modern-funk drummer Stanton Moore. Theryl "Houseman" de Clouet adds supersonic soul vocals to five of the 14 tracks and Roger Lewis of the Dirty Dozen Brass Band injects his gritty baritone saxophone into two tunes.
No, we never did think of Galactic as just another bunch of tattooed backwoods guitar slingers, ready at a moment's notice to thrill themselves -- and maybe others, too - with endless dueling guitar jams and paeans to the Southern way of life. Nor did we quite peg Moore, bassist Robert Mercurio, guitarist Jeff Raines and the rest of the squad as sunshine-mellow musicians intent on devising the perfect musical accompaniment to psychedelic experiences. (Not that there's anything wrong with that.)
As demonstrated by their convincing recordings and raucous, bracing shows, Galactic instead occupy a sort of middle ground between groove-jazz territory -- as exemplified by Medeski, Martin and Wood, Charlie Hunter and the Jazz Mandolin Project -- and the realm of bona-fide jam bands like Phish, Widespread Panic and Blues Traveler. (Galactic has shared stages with several of the neo-Dead types on the H.O.R.D.E. tour and elsewhere.) Even more integral to the group's concept is the irresistible urban funk practiced by the Meters, James Brown and the '60s soul-jazz artists who were signed to the Blue Note label.
"It depends on how you define 'jam band,'" muses bassist Robert Mercurio. "‘Jam band' means Southern hippie-rock to a lot of people. I don't think we're like that at all. We tour a lot, play long shows and try to improvise a lot. That's where I think we crossover with the Widespread stuff."
To Mercurio, Galactic's penchant for regularly departing from a tune's road map to explore uncharted terrain is the chief trait the band has in common with the new-school jammers. "That's the essence of a jam band," he asserts. "I think it's more about that than it is a particular style. Some nights it'll be really raging and the next night it's really mellow. It's really about what comes out."
Moore -- a New Orleans native who hooked up with the Washington, D.C.-bred Mercurio, Raines and organ/piano man Rich Vogel in the early '90s -- has a similar take on the "to jam or not to jam" question: "We definitely don't think it's a musical connection," he declaims. "It's a similar approach where you just hit the road as much as you can and develop a large fan base without the help of too much radio or MTV. We consider ourselves a New Orleans funk band who happen to tour and improvise on stage. We try to allow that spontaneity to happen, as opposed to just getting up there and playing radio hits."
Airplay, however, may be a real possibility this time around for Galactic (whose growing list of supporters includes Adam Duritz of Counting Crows, Sean Lennon, Jon Bon Jovi and actors Matthew McConaughey, Vince Vaughn and Emilio Estevez). The potential for big-time exposure is keyed to the harder-edged sound -- and increased emphasis on vocals -- heard on "Late For the Future," a record produced by knob man Nick Sansano (Sonic Youth, Manic Street Preachers).
With its mutating horn section now trimmed to saxophonist Ben Ellman, the sextet opens the CD with the six-string scorch, juicy Hammond B-3 melody and percolating rhythms of "Black Eyed Pea," which originally appeared on 1995's "Is That Jazz" compilation on acid-jazz label Ubiquity. "We kind of reworked it, and gave it a new tone and sound," Mercurio says. A gritty two-sax section anchors the sounds of "Baker's Dozen" and the Middle Eastern-tinged "Hit the Wall," the former a direct nod to the best-known of the modern Crescent City street bands.
"That's a little shout-out for the Dirty Dozen," says Moore. "It's cool that Roger Lewis came in and played on it. It kind of gave it the seal of approval." Drum loops and other effects are heard on the free-leaning "Two Clowns."
The Houseman, a permanent special guest since contributing two tracks to "Coolin' Off," Galactic's 1996 debut, lends a sense of impassioned urgency with his in-your-face singing on "Thrill," "Century City," "Running Man," "Vilified" (a duet with ex-Anders Osborne Orchestra singer Theresa Andersson) and "Action Speaks Louder Than Words."
De Clouet's profile within the band has gradually risen over the years, and his voice was heard on three tracks from 1998's "Crazyhorse Mongoose." But there's never been a vocals-versus-instrumentals debate within the band, Moore says. "That's just been a natural progression," he testifies. "We worked a long time on the vocals for this one and really got it to where we felt comfortable. We kind of enjoy both aspects of it. I think a lot of people like the variety."

domain: entertainment


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The article of Angle Steel Stool Company was posted on November 29, 2018 at 9:00 am. This article is published on the Stool category. Angle Steel Stool Company is labelled with Angle Steel Stool Company, Angle, Steel, Stool, Company..
Anglean•gle1 (ang′gəl),USA pronunciation n., v., -gled, -gling.
- the space within two lines or three or more planes diverging from a common point, or within two planes diverging from a common line.
- the figure so formed.
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30ʺ, which is read as 12 degrees, 10 minutes, and 30 seconds.
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a projecting corner: the angles of a building.
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- See angle iron (def. 2).
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slant: She angled her column toward teenagers.
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Steelsteel (stēl),USA pronunciation n.
- any of various modified forms of iron, artificially produced, having a carbon content less than that of pig iron and more than that of wrought iron, and having qualities of hardness, elasticity, and strength varying according to composition and heat treatment: generally categorized as having a high, medium, or low-carbon content.
- a thing or things made of this metal.
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- steels, stocks or bonds of companies producing this metal.
- a sword.
- a rounded rod of ridged steel, fitted with a handle and used esp. for sharpening knives.
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- to cause to resemble steel in some way.
- to render insensible, inflexible, unyielding, determined, etc.: He steeled himself to perform the dangerous task.
Stoolstool (sto̅o̅l),USA pronunciation n.
- a single seat on legs or a pedestal and without arms or a back.
- a short, low support on which to stand, step, kneel, or rest the feet while sitting.
- [Hort.]the stump, base, or root of a plant from which propagative organs are produced, as shoots for layering.
- the base of a plant that annually produces new stems or shoots.
- a cluster of shoots or stems springing up from such a base or from any root, or a single shoot or layer.
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- an artificial duck or other bird, usually made from wood, used as a decoy by hunters.
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- the fecal matter evacuated at each movement of the bowels.
- the sill of a window. See diag. under double-hung.
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- the sacred chair of certain African chiefs, symbolic of their kingship.
- fall between two stools, to fail, through hesitation or indecision, to select either of two alternatives.
- to put forth shoots from the base or root, as a plant;
form a stool.
- to turn informer;
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Companycom•pa•ny (kum′pə nē),USA pronunciation n., pl. -nies, v., -nied, -ny•ing.
- a number of individuals assembled or associated together;
group of people.
- a guest or guests: We're having company for dinner.
- an assemblage of persons for social purposes.
association: I always enjoy her company.
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- (cap.) the members of a firm not specifically named in the firm's title: George Higgins and Company.
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- any relatively small group of soldiers.
- [Army.]a basic unit with both tactical and administrative functions.
- a unit of firefighters, including their special apparatus: a hook-and-ladder company.
- Also called ship's company. a ship's crew, including the officers.
- a medieval trade guild.
- the Company, [Informal.]a nation's major intelligence-gathering and espionage organization, as the U.S. Central Intelligence Agency.
- keep company:
- to associate with;
be a friend of.
- [Informal.]to go together, as in courtship: My sister has been keeping company with a young lawyer.
- part company:
- to cease association or friendship with: We parted company 20 years ago after the argument.
- to take a different or opposite view;
differ: He parted company with his father on politics.
- to separate: We parted company at the airport.
- [Archaic.]to associate.
- [Archaic.]to accompany.
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SKF 61805 bearing
SKF 61805 bearing | Deep Groove Ball Bearing | 25x37x7Best Price
- Bearing number : 61805
- Size (mm) : 25x37x7
- Brand : SKF
- Bore Diameter (mm) : 25
- Outer Diameter (mm) : 37
- Width (mm) : 7
- d - 25 mm
- D - 37 mm
- B - 7 mm
- d1 - - 28.5 mm
- D1 - - 33.15 mm
- r1,2 - min. - 0.6 mm
- da - min. - 27 mm
- Da - max. - 35 mm
- ra - max. - 0.3 mm
- Basic dynamic load rating - C - 4.4 kN
- Basic static load rating - C0 - 2.6 kN
- Fatigue load limit - Pu - 0.125 kN
- Reference speed - 38000 r/min
- Limiting speed - 24000 r/min
- Calculation factor - kr - 0.015
- Calculation factor - f0 - 14.2
- Mass bearing - 0.0218 kg
Deep groove ball bearings, single row 61805
Bearing dimensions and specification in SKF catalogue:
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Garden Rectangular Planter Ideas Image
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domain: hobby


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CRYSVITA was evaluated in 2 clinical studies of patients with TIO. Studies 6 and 7 were Phase 2, open-label studies in adults with TIO aged 33 to 73 years in which patients received CRYSVITA for at least 88 weeks.
|ADVERSE REACTIONS REPORTED IN CRYSVITA-TREATED ADULT PATIENTS IN STUDY 6 AND STUDY 7|
(N=27) n (%)
|Tooth abscessa||5 (19)|
|Muscle spasms||5 (19)|
|Injection site reactionb||4 (15)|
|Vitamin D deficiency||2 (7)|
|Restless legs syndrome||2 (7)|
n, number of patients with an event; N, total number of patients who received at least 1 dose of CRYSVITA.
- aTooth abscess includes: tooth abscess and toothache.
- bInjection site reaction includes: injection site reaction, injection site pain, and injection site swelling.
- cRash includes: rash and rash papular.
In the Phase 2 studies, 22% of patients experienced a hypersensitivity reaction, which were mild or moderate in severity.1
In the Phase 2 studies, 7% of patients experienced hyperphosphatemia, which was managed with dose reduction.1
Injection site reactions
In the Phase 2 studies, 15% of patients reported an injection site reaction (e.g., injection site reaction, injection site pain, and injection site swelling). Injection site reactions were generally mild in severity, required no treatment, and resolved in all cases.1
Restless legs syndrome
In the Phase 2 studies, 7% of patients experienced symptoms of restless legs syndrome, which were mild and did not require treatment interruption.1
No patients withdrew from the study due to adverse reactions.
There were no significant changes in frequency, type, or severity of adverse reactions reported through 144 weeks, compared with prior clinical studies in patients receiving CRYSVITA (N=162).
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of the antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to CRYSVITA in the studies described in this website with the incidence of antibodies in other studies or to other products may be misleading.
14% of patients in Study 6 and no patients in Study 7 developed anti-drug antibodies (ADA) with no neutralizing antibody detected, and ADA did not impact drug efficacy.1
CRYSVITA (burosumab-twza) US Prescribing Information; June 2020.

domain: medical


text:
Google Advertising versus Non-advertising revenue 2016-2022.
The chart above compares the advertising and non-advertising revenue of Google from 2016 to 2022. While Google’s revenue from advertising has continued to grow at an impressive rate, it has also experienced significant growth in its revenue from non-advertising sources. In 2022, Google experienced slightly more than 17% growth in its revenue from the non-advertising sources. The company generated $55.3 billion from non-advertising and $224.5 billion from advertising in fiscal 2022.
Alphabet (NASDAQ: GOOG, GOOGL) has been experiencing a sharp rise in its non-advertising revenue. Its business is divided into two reportable segments that include Google & Other Bets.
Alphabet’s main source of revenue from the Google segment is advertising which accounted for more than 85% of the company’s entire revenue in 2018. In 2019, the share of advertising revenue has declined to less than 85% of the company’s net revenue and in 2021 to around 81% of the company’s total revenues. It dropped to 79.4% in fiscal 2022.
The share of non-advertising revenue in the net revenue of Alphabet (Google) has kept rising over the past several years. Total non-advertising revenue of Google grew by more than 90% from 2016 to 2018. According to 2018 form 10K of Alphabet, non-advertising revenue in 2016 stood at $10.6 billion which grew to $19.9 billion in 2018. The fourth quarter non-advertising revenue of Alphabet in 2018 reached $6.5 billion compared to $4.97 billion in 2017 Q4.
In fiscal 2021, Alphabet (parent company of Google) experienced a sharp jump in its total net revenues. The net revenues of the company grew by 41% driven mainly by growth in its revenues Google services and Google cloud. Its total net revenues increased by around $75 billion reaching $257.637 billion. The share of advertising revenues of Google in its total net revenues was $209.5 billion in 2021 compared to $146.9 billion in the previous year.The non-advertising revenues of Google increased to $47.24 billion in 2021 compared to $34.8 billion in the previous year. Alphabet’s total revenues from other bets also increased to $753 million in 2021 from $657 million in 2020.
While Google’s non-advertising revenue grew 34% in 2020 compared to 2019, it increased by around 36% in 2021 compared to 2020. Its growth rate has continued to improve over the past several years. In 2019, Google’s non-advertising revenue had increased 30% compared to 2018.
Here is how much Google generated from non-advertising businesses during 2016-2022:
Google’s Non-Advertising and Advertising Revenues in millions 2017-2021
|Year||Non-Ad Revenue ($mn)||%change in non-ad revenue||Ad Revenues (m)|
The sources of non-advertising revenues of Google include sales of apps, in-app purchases, digital content products, and hardware; and licensing and service fees, including subscription fees for Google Cloud offerings.
The following table shows the quarterly non-ad revenue of Google for fiscal 2019. Sums are in millions.
|2019/Quarter||Non ad revenue (millions)|
As you can see, Google’s non-advertising revenue has gained significantly compared to the previous year in 2019. Total revenue of Google during fiscal 2019 at the end of the third quarter was $18,058 million compared to $13,419 million during the same period previous year. Net revenue of Google during the fourth quarter of 2019 grew to $45.8 billion compared to $39 billion in 2018.
Google is the leading search engine in the world with the largest market share. Its core source of revenue is digital advertising where it leads the industry. The parent company of Google is Alphabet which also operates other businesses (collectively termed as other bets) apart from Google. Google is the largest business segment of Alphabet which has enjoyed revenue growth from cloud as well as YouTube ads in recent years. The company has its headquarters in Mountain View, California, United States. The CEO of Alphabet is Sundar Pichai. Google was founded on 4th September, 1998 at Menlo Park, California, United States. The head office of Google at Mountainview, California, is known as Googleplex.


text:
Duloxetine 40 mg gastro-resistant capsules, hard
Each capsule contains 40 mg of duloxetine (as hydrochloride).
Excipient with known effect:
Each 40 mg capsule contains 128.33 mg sucrose.
For the full list of excipients, see section 6.1.
Gastro-resistant capsule, hard.
40 mg: Opaque blue cap and opaque orange body size '2' (17.80 ± 0.40 mm) hard gelatin capsule imprinted with 'H' on cap and 'D3' on body with black ink, filled with white to off white colored pellets.
Duloxetine is indicated for women for the treatment of moderate to severe Stress Urinary Incontinence (SUI).
Duloxetine is indicated in adults.
For further information see section 5.1.
The recommended dose of Duloxetine is 40 mg twice daily without regard to meals. After 2-4 weeks of treatment, patients should be re-assessed in order to evaluate the benefit and tolerability of the therapy. Some patients may benefit from starting treatment at a dose of 20 mg twice daily for two weeks before increasing to the recommended dose of 40 mg twice daily. Dose escalation may decrease, though not eliminate, the risk of nausea and dizziness.
However, limited data are available to support the efficacy of Duloxetine20 mg twice daily.
The efficacy of Duloxetine has not been evaluated for longer than 3 months in placebo-controlled studies. The benefit of treatment should be re-assessed at regular intervals.
Combining Duloxetine with a pelvic floor muscle training (PFMT) programme may be more effective than either treatment alone. It is recommended that consideration be given to concomitant PFMT.
Duloxetine must not be used in women with liver disease resulting in hepatic impairment (see sections 4.3 and 5.2).
No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/min). Duloxetine must not be used in patients with severe renal impairment (creatinine clearance <30 ml/min; see section 4.3).
The safety and efficacy of duloxetine for the treatment of stress urinary incontinence has not been studied. No data are available.
Caution should be exercised when treating the elderly.
Discontinuation of treatment
Abrupt discontinuation should be avoided. When stopping treatment with Duloxetine the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered.
Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.
Method of administration
For oral use.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Liver disease resulting in hepatic impairment (see section 5.2).
Duloxetine should not be used in combination with nonselective, irreversible monoamine oxidase inhibitors - MAOIs (see section 4.5).
Duloxetine should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacin since the combination results in elevated plasma concentrations of duloxetine (see section 4.5).
Severe renal impairment (creatinine clearance <30 ml/min) (see section 4.4).
The initiation of treatment with Duloxetine is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8).
Mania and seizures
Duloxetine should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and/or seizures.
As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with duloxetine treatment, particularly with concomitant use of other serotonergic agents (including SSRIs, SNRIs tricyclic antidepressants or triptans), with agents that impair metabolism of serotonin such as MAOIs, or with antipsychotics or other dopamine antagonists that may affect the serotonergic neurotransmitter systems (see sections 4.3 and 4.5), or with buprenorphine/opioids medicines.
Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).
If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be consider depending on the severity of the symptoms.
If concomitant treatment with duloxetine and other serotonergic agents that may affect the serotonergic and/or dopaminergic neurotransmitter systems in clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
St John's wort
Adverse reactions may be more common during concomitant use of Duloxetine and herbal preparations containing St John's wort (Hypericum perforatum).
Mydriasis has been reported in association with duloxetine, therefore, caution should be used when prescribing duloxetine in patients with increased intraocular pressure, or those at risk of acute narrow-angle glaucoma.
Blood pressure and heart rate
Duloxetine has been associated with an increase in blood pressure and clinically significant hypertension in some patients. This may be due to the noradrenergic effect of duloxetine. Cases of hypertensive crisis have been reported with duloxetine, especially in patients with pre-existing hypertension. Therefore, in patients with known hypertension and/or other cardiac disease, blood pressure monitoring is recommended, especially during the first month of treatment. Duloxetine should be used with caution in patients whose conditions could be compromised by an increased heart rate or by an increase in blood pressure. Caution should also be exercised when duloxetine is used with medicinal products that may impair its metabolism (see section 4.5). For patients who experience a sustained increase in blood pressure while receiving duloxetine either dose reduction or gradual discontinuation should be considered (see section 4.8). In patients with uncontrolled hypertension duloxetine should not be initiated (see section 4.3).
Increased plasma concentrations of duloxetine occur in patients with severe renal impairment on haemodialysis (creatinine clearance <30 ml/min). For patients with severe renal impairment, see section 4.3. See section 4.2 for information on patients with mild or moderate renal dysfunction.
There have been reports of bleeding abnormalities, such as ecchymoses, purpura and gastrointestinal haemorrhage with selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs), including duloxetine. Duloxetine may increase the risk of postpartum haemorrhage (see section 4.6). Caution is advised in patients taking anticoagulants and/or medicinal products known to affect platelet function (e.g. NSAIDs or acetylsalicylic acid (ASA)), and in patients with known bleeding tendencies.
Discontinuation of treatment
Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8). In a clinical trial, adverse events seen on abrupt treatment discontinuation occurred in approximately 44% of patients treated with Duloxetineand 24% of patients taking placebo.
The risk of withdrawal symptoms seen with SSRI's and SNRI's may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. The most commonly reported reactions are listed in section 4.8. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that duloxetine should be gradually tapered when discontinuing treatment over a period of no less than 2 weeks, according to the patient's needs (see section 4.2).
Hyponatraemia has been reported when administering Duloxetine, including cases with serum sodium lower than 110 mmol/l. Hyponatraemia may be due to a syndrome of inappropriate anti-diuretic hormone secretion (SIADH). The majority of cases of hyponatraemia were reported in the elderly, especially when coupled with a recent history of, or condition pre-disposing to, altered fluid balance. Caution is required in patients at increased risk for hyponatraemia, such as elderly, cirrhotic, or dehydrated patients or patients treated with diuretics.
Depression, suicidal ideation and behaviour
Although Duloxetine is not indicated for the treatment of depression, its active ingredient (duloxetine) also exists as an antidepressant medicinal product. Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal thoughts prior to commencement of treatment are known to be at a greater risk of suicidal thoughts or suicidal behaviour, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant medicinal products in psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.
Cases of suicidal thoughts and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.8). Physicians should encourage patients to report any distressing thoughts or feelings or depressive symptoms at any time. If while on Duloxetine therapy, the patient develops agitation or depressive symptoms, specialised medical advice should be sought, as depression is a serious medical condition. If a decision to initiate antidepressant pharmacological therapy is taken, the gradual discontinuation of Duloxetine is recommended (see section 4.2).
Use in children and adolescents under 18 years of age
Duloxetine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempts and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger), were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Medicinal products containing duloxetine
Duloxetine is used under different trademarks in several indications (treatment of diabetic neuropathic pain, major depressive disorder, generalised anxiety disorder and stress urinary incontinence). The use of more than one of these products concomitantly should be avoided.
Hepatitis/increased liver enzymes
Cases of liver injury, including severe elevations of liver enzymes (>10 times upper limit of normal), hepatitis and jaundice have been reported with duloxetine (see section 4.8). Most of them occurred during the first months of treatment. The pattern of liver damage was predominantly hepatocellular. Duloxetine should be used with caution in patients treated with other medicinal products associated with hepatic injury.
The use of duloxetine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRIs.
Duloxetine hard gastro-resistant capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially 'sodium-free'.
Monoamine oxidase inhibitors (MAOIs): Due to the risk of serotonin syndrome, duloxetine should not be used in combination with non-selective irreversible monoamine oxidase inhibitors (MAOIs), or within at least 14 days of discontinuing treatment with an MAOI. Based on the half-life of duloxetine, at least 5 days should be allowed after stopping Duloxetine before starting an MAOI (see section 4.3).
The concomitant use of duloxetine with selective, reversible MAOIs, like moclobemide, is not recommended (see section 4.4). The antibiotic linezolid is a reversible non-selective MAOI and should not be given to patients treated with duloxetine (see section 4.4).
Inhibitors of CYP1A2: Because CYP1A2 is involved in duloxetine metabolism, concomitant use of duloxetine with potent inhibitors of CYP1A2 is likely to result in higher concentrations of duloxetine. Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma clearance of duloxetine by about 77% and increased AUC0-t 6-fold. Therefore Duloxetine should not be administered in combination with potent inhibitors of CYP1A2 like fluvoxamine (see section 4.3).
CNS medicinal products: Caution is advised when Duloxetine is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).
Serotonergic agents: In rare cases, serotonin syndrome has been reported in patients using SSRIs/SNRIs concomitantly with serotonergic agents. Caution is advisable if duloxetine is used concomitantly with serotonergic agents like SSRIs, SNRIs, tricyclic antidepressants like clomipramine or amitriptyline, MAOIs like moclobemide or linezolid, St John's wort (Hypericum perforatum) or triptans, tramadol, pethidine and tryptophan (see section 4.4).
Effect of duloxetine on other medicinal products
Medicinal products metabolised by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).
Medicinal products metabolised by CYP2D6: Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered at a dose of 60 mg twice daily with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. The co-administration of duloxetine (40 mg twice daily) increases steady state AUC of tolterodine (2 mg twice daily) by 71 %, but does not affect the pharmacokinetics of its active 5-hydroxyl metabolite and no dosage adjustment is recommended. Caution is advised if Duloxetine is co-administered with medicinal products that are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol).
Oral contraceptives and other steroidal agents: Results of in vitro studies demonstrate that duloxetine does not induce the catalytic activity of CYP3A. Specific in vivo drug interaction studies have not been performed.
Anticoagulants and antiplatelet agents: Caution should be exercised when duloxetine is combined with oral anticoagulants or antiplatelet agents due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction. Furthermore, increases in INR values have been reported when duloxetine was co-administered to patients treated with warfarin. However, concomitant administration of duloxetine with warfarin under steady state conditions, in healthy volunteers, as part of a clinical pharmacology study, did not result in a clinically significant change in INR from baseline or in the pharmacokinetics of R- or S-warfarin.
Effects of other medicinal products on duloxetine
Antacids and H2 antagonists: Co-administration of duloxetine with aluminium- and magnesium-containing antacids or with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.
Inducers of CYP1A2: Population pharmacokinetic studies analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.
Buprenorphine/opioids medicines: as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
In animal studies duloxetine had no effect on male fertility, and effects in females were only evident at doses that caused maternal toxicity.
Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure (see section 5.3).
Two large observational studies do not suggest an overall increased risk of major congenital malformation (one from the US including 2,500 exposed to duloxetine during the first trimester and one from the EU including 1,500 exposed to duloxetine during the first trimester). The analysis on specific malformations such as cardiac malformations shows inconclusive results.
In the EU study, maternal exposure to duloxetine during late pregnancy (at any time from 20 weeks gestational age to delivery) was associated with an increased risk for preterm birth (less than 2-fold, corresponding to approximately 6 additional premature births per 100 women treated with duloxetine late in pregnancy). The majority occurred between 35 and 36 weeks of gestation. This association was not seen in the US study.
The US observational data have provided evidence of an increased risk (less than 2- fold) of postpartum haemorrhage following duloxetine exposure within the month prior to birth.
Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN to SNRI treatment, this potential risk cannot be ruled out with duloxetine taking into account the related mechanism of action (inhibition of the re-uptake of serotonin).
As with other serotonergic medicinal products, discontinuation symptoms may occur in the neonate after maternal duloxetine use near term. Discontinuation symptoms seen with duloxetine may include hypotonia, tremor, jitteriness, feeding difficulty, respiratory distress and seizures. The majority of cases have occurred either at birth or within a few days of birth.
Duloxetine should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus. Women should be advised to notify their physician if they become pregnant, or intend to become pregnant, during therapy.
Duloxetine is very weakly excreted into human milk based on a study of 6 lactating patients, who did not breast feed their children. The estimated daily infant dose on a mg/kg basis is approximately 0.14% of the maternal dose (see section 5.2). As the safety of duloxetine in infants is not known, the use of Duloxetine while breast- feeding is not recommended.
No studies on the effects on the ability to drive and use machines have been performed. Duloxetine may be associated with sedation and dizziness. Patients should be instructed that if they experience sedation or dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.
a. Summary of the safety profile
The most commonly reported adverse events in patients treated with Duloxetine in clinical trials in SUI and other lower urinary tract disorders were nausea, dry mouth fatigue and constipation. The data analysis of four 12-week, placebo-controlled clinical trials in patients with SUI, including 958 duloxetine-treated and 955 placebo- treated patients, showed that the onset of the reported adverse events typically occurred in the first week of therapy. However, the majority of the most frequent adverse events were mild to moderate and resolved within 30 days of occurrence (e.g. nausea).
b. Tabulated summary of adverse reactions
Table 1 gives the adverse reactions observed from spontaneous reporting and in placebo-controlled clinical trials.
Table 1: Adverse reactions
Frequency estimate: Very common (≥ 1/10), common (≥ 1/100 to <1/10), uncommon (≥ 1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and infestations
Immune system disorders
Metabolism and nutrition disorders
Hyperglycaemia (reported especially in diabetic patients)
Suicidal ideation 5,7
Aggression and anger4,6
Nervous system disorders
Disturbance in attention
Poor quality sleep
Restless legs syndrome
Ear and labyrinth disorders
Supra-ventricular arrhythmia, mainly atrial fibrillation6
Blood pressure increase3
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease10
Elevated liver enzymes (ALT, AST, alkaline phosphatase)
Acute liver injury
Skin and subcutaneous tissue disorders
Increased tendency to bruise
Musculoskeletal and connective tissue disorders
Renal and urinary disorders
Urine odour abnormal
Urine flow decreased
Reproductive system and breast disorders
General disorders and administration site conditions
Blood cholesterol increased
Blood potassium increased
1 Cases of convulsion and cases of tinnitus have also been reported after treatment discontinuation.
2 Cases of orthostatic hypotension and syncope have been reported especially at the initiation of treatment.
3 See section 4.4.
4 Cases of aggression and anger have been reported particularly early in treatment or after treatment discontinuation.
5 Cases of suicidal ideation and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.4).
6 Estimated frequency of post-marketing surveillance reported adverse reactions; not observed in placebo-controlled clinical trials.
7 Not statistically significantly different from placebo.
8 Falls were more common in the elderly (≥ 65 years old).
9 Estimated frequency based on all clinical trial data.
10 Estimated frequency based on placebo-controlled clinical trials.
c. Description of selected adverse reactions
Discontinuation of duloxetine (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia or electric shock-like sensations, particularly in the head), sleep disturbances (including insomnia and intense dreams), fatigue, somnolence, agitation or anxiety, nausea and/or vomiting, tremor, headache, myalgia, irritability, diarrhoea, hyperhydrosis and vertigo are the most commonly reported reactions.
Generally, for SSRIs and SNRIs, these events are mild to moderate and self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when duloxetine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).
The heart rate-corrected QT interval in duloxetine-treated patients did not differ from that seen in placebo-treated patients. No clinically significant differences were observed for QT, PR, QRS, or QTcB measurements between duloxetine-treated and placebo-treated patients.
In the 12 week acute phase of three clinical trials of duloxetine in patients with diabetic neuropathic pain, small but statistically significant increases in fasting blood glucose were observed in duloxetine-treated patients. HbA1c was stable in both duloxetine-treated and placebo-treated patients. In the extension phase of these studies, which lasted up to 52 weeks, there was an increase in HbA1c in both the duloxetine and routine care groups, but the mean increase was 0.3% greater in the duloxetine-treated group. There was also a small increase in fasting blood glucose and in total cholesterol in duloxetine-treated patients while those laboratory tests showed a slight decrease in the routine care group.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Cases of overdoses, alone or in combination with other medicinal products, with duloxetine doses of 5400 mg were reported. Some fatalities have occurred, primarily with mixed overdoses, but also with duloxetine alone at a dose of approximately 1000 mg. Signs and symptoms of overdose (duloxetine alone or in combination with other medicinal products) included somnolence, coma, serotonin syndrome, seizures, vomiting and tachycardia.
No specific antidote is known for duloxetine but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. A free airway should be established. Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures.
Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption. Duloxetine has a large volume of distribution and forced diuresis, haemoperfusion, and exchange perfusion are unlikely to be beneficial.
Pharmacotherapeutic group: Other antidepressants. ATC code: N06AX21.
Mechanism of action
Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.
In animal studies, increased levels of 5-HT and NE in the sacral spinal cord, lead to increased urethral tone via enhanced pudendal nerve stimulation to the urethral striated sphincter muscle only during the storage phase of the micturition cycle. A similar mechanism in women is believed to result in stronger urethral closure during urine storage with physical stress that could explain the efficacy of duloxetine in the treatment of women with SUI.
Clinical efficacy and safety
The efficacy of duloxetine 40 mg given twice daily in the treatment of SUI was established in four double-blind, placebo-controlled studies that randomised 1913 women (22 to 83 years) with SUI; of these, 958 patients were randomised to duloxetine and 955 to placebo. The primary efficacy measures were Incontinence Episode Frequency (IEF) from diaries and an incontinence specific quality of life questionnaire score (I-QOL).
Incontinence Episode Frequency: In all four studies the duloxetine-treated group had a 50% or greater median decrease in IEF compared with 33% in the placebo-treated group. Differences were observed at each visit after 4 weeks (duloxetine 54% and placebo 22%), 8 weeks (52% and 29%), and 12 weeks (52% and 33%) of medication.
In an additional study limited to patients with severe SUI, all responses with duloxetine were achieved within 2 weeks.
The efficacy of Duloxetine has not been evaluated for longer than 3 months in placebo-controlled studies. The clinical benefit of Duloxetine compared with placebo has not been demonstrated in women with mild SUI, defined in randomised trials as those with IEF < 14 per week. In these women, Duloxetine may provide no benefit beyond that afforded by more conservative behavioural interventions.
Quality of Life: Incontinence Quality of Life (I-QOL) questionnaire scores were significantly improved in the duloxetine-treated patient group compared with the placebo-treated group (9.2 versus 5.9 score improvement, p<0.001). Using a global improvement scale (PGI), significantly more women using duloxetine considered their symptoms of stress incontinence to be improved with treatment compared with women using placebo (64.6% versus 50.1%, p<0.001).
Duloxetine and Prior Continence Surgery: There are limited data that suggest that the benefits of Duloxetine are not diminished in women with stress urinary incontinence who have previously undergone continence surgery.
Duloxetine and Pelvic Floor Muscle Training (PFMT): During a 12-week blinded, randomised, controlled study, Duloxetine demonstrated greater reductions in IEF compared with either placebo treatment or with PFMT alone. Combined therapy (duloxetine + PFMT) showed greater improvement in both pad use and condition- specific quality of life measures than Duloxetine alone or PFMT alone.
The European Medicines Agency has waived the obligation to submit the results of studies with duloxetine in all subsets of the paediatric population in the treatment of stress urinary incontinence. See section 4.2 for information on paediatric use.
Duloxetine is administered as a single enantiomer. Duloxetine is extensively metabolised by oxidative enzymes (CYP1A2 and the polymorphic CYP2D6), followed by conjugation. The pharmacokinetics of duloxetine demonstrate large intersubject variability (generally 50-60%), partly due to gender, age, smoking status and CYP2D6 metaboliser status.
Absorption: Duloxetine is well absorbed after oral administration with a Cmax occurring 6 hours post dose. The absolute oral bioavailability of duloxetine ranged from 32% to 80% (mean of 50%). Food delays the time to reach the peak concentration from 6 to 10 hours and it marginally decreases the extent of absorption (approximately 11 %). These changes do not have any clinical significance.
Distribution: Duloxetine is approximately 96% bound to human plasma proteins.
Duloxetine binds to both albumin and alpha-l acid glycoprotein. Protein binding is not affected by renal or hepatic impairment.
Biotransformation: Duloxetine is extensively metabolised and the metabolites are excreted principally in urine. Both cytochromes P450-2D6 and 1A2 catalyse the formation of the two major metabolites glucuronide conjugate of 4-hydroxy duloxetine and sulfate conjugate of 5-hydroxy 6-methoxy duloxetine. Based upon in vitro studies, the circulating metabolites of duloxetine are considered pharmacologically inactive. The pharmacokinetics of duloxetine in patients who are poor metabolisers with respect to CYP2D6 has not been specifically investigated.
Limited data suggest that the plasma levels of duloxetine are higher in these patients.
Elimination: The elimination half-life of duloxetine ranges from 8 to 17 hours (mean of 12 hours). After an intravenous dose the plasma clearance of duloxetine ranges from 22 l/hr to 46 l/hr (mean of 36 l/hr). After an oral dose the apparent plasma clearance of duloxetine ranges from 33 to 261 l/hr (mean 101 l/hr).
Gender: Pharmacokinetic differences have been identified between males and females (apparent plasma clearance is approximately 50% lower in females). Based upon the overlap in the range of clearance, gender-based pharmacokinetic differences do not justify the recommendation for using a lower dose for female patients.
Age: Pharmacokinetic differences have been identified between younger and elderly females (≥ 65 years) (AUC increases by about 25% and half-life is about 25% longer in the elderly), although the magnitude of these changes is not sufficient to justify adjustments to the dose. As a general recommendation, caution should be exercised when treating the elderly (see sections 4.2 and 4.4).
Renal impairment: End stage renal disease (ESRD) patients receiving dialysis had 2- fold higher duloxetine Cmax and AUC values compared with healthy subjects.
Pharmacokinetic data on duloxetine is limited in patients with mild or moderate renal impairment.
Hepatic impairment: Moderate liver disease (Child Pugh Class B) affected the pharmacokinetics of duloxetine. Compared with healthy subjects, the apparent plasma clearance of duloxetine was 79% lower, the apparent terminal half-life was 2.3 times longer, and the AUC was 3.7 times higher in patients with moderate liver disease. The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic insufficiency.
Breast-feeding mothers: The disposition of duloxetine was studied in 6 lactating women who were at least 12-weeks postpartum. Duloxetine is detected in breast milk, and steady-state concentrations in breast milk are about one-fourth those in plasma.
The amount of duloxetine in breast milk is approximately 7 µ g/day while on 40 mg twice daily dosing. Lactation did not influence duloxetine pharmacokinetics.
Duloxetine was not genotoxic in a standard battery of tests and was not carcinogenic in rats.
Multinucleated cells were seen in the liver in the absence of other histopathological changes in the rat carcinogenicity study. The underlying mechanism and the clinical relevance are unknown. Female mice receiving duloxetine for 2 years had an increased incidence of hepatocellular adenomas and carcinomas at the high dose only (144 mg/kg/day), but these were considered to be secondary to hepatic microsomal enzyme induction. The relevance of this mouse data to humans is unknown. Female rats receiving duloxetine before and during mating and early pregnancy had a decrease in maternal food consumption and body weight, oestrous cycle disruption, decreased live birth indices and progeny survival, and progeny growth retardation at systemic exposure levels estimated to be at the most at maximum clinical exposure (AUC). In an embryotoxicity study in the rabbit, a higher incidence of cardiovascular and skeletal malformations was observed at systemic exposure levels below the maximum clinical exposure (AUC). No malformations were observed in another study testing a higher dose of a different salt of duloxetine. In pre/postnatal toxicity study in the rat, duloxetine induced adverse behavioural effects in the offspring at systemic exposure levels below maximum clinical exposure (AUC).
Studies in juvenile rats reveal transient effects on neurobehaviour, as well as significantly decreased body weight and food consumption; hepatic enzyme induction; and hepatocellular vacuolation at 45 mg/kg/day. The general toxicity profile of duloxetine in juvenile rats was similar to that in adult rats. The no-adverse effect level was determined to be 20 mg/kg/day.
Sugar spheres (containing maize starch and sucrose)
Hypromellose 2910 (E464)
Crospovidone (type B)
Carboxy methyl ethyl cellulose
Titanium dioxide (E171)
Polysorbate 80 (E433)
40 mg Capsule shell:
Titanium dioxide (E171)
Indigo carmine (E132).
Iron oxide yellow (E172)
Iron oxide red (E172)
Black iron oxide (E172)
This medicine does not require any special storage conditions.
Duloxetine is available in:
40 mg: blister packs of 7, 10, 14, 20, 28, 30, 50, 56, 84, 98, 100 and 500 capsules.
Not all pack sizes may be marketed.
No special requirements.
Congress House, 14 Lyon Road
Harrow, Middlesex HA1 2EN


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This product is not intended for use on persons under the age of 16.
Temporary "black henna" tattoos may increase your risk of allergy.
Do not colour your hair if:
The developer contains hydrogen peroxide.
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- You have ever experienced any reaction after colouring your hair.
- You have experienced a reaction to a temporary "black henna" tattoo in the past.
The colourant cream contains phenylenediamines, resorcinol and ammonia.
Avoid contact with eyes and rinse immediately and thoroughly if product comes into contact with them.
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Rinse hair well after application.
Keep out of reach of children.
- 1x bottle of developer 60ml.
- 1x tube of colourant cream 40ml.
- 1x after colour conditioner bottle 40ml.
- 1x instruction leaflet / 1x pair of gloves.
Water, Paraffinum liquidum, Cetearyl alcohol, Ethanolamine, Steareth-20, Ammonium hydroxide, Steareth-2, Resorcinol, 2-4-diaminophenoxyethanol HCI, p-aminophenol, Sodium metabisulfite, 6-hydroxyindole, Thioglycerin, Toluene-2-5-diamine, Polyquaternium-6, 2-methylresorcinol, Camellia oleifera seed oil, 2-methyl-5-hydroxyethylaminophenol, Pentasodium pentetate, Erythorbic acid, Fragrance. (F.I.L C52818/2).
Water, Hydrogen peroxide, Cetearyl alcohol, Sodium stannate, Trideceth-2 carboxamide mea, Pentasodium pentetate, Phosphoric acid, Ceteareth-25, Tetrasodium pyrophosphate, Glycerin. (F.I.L C13169/25).
After colour conditioner:
Water, Cetearyl alcohol, amodimethicone, Behentrimonium chloride, Titanium dioxide, Mica, Nacre powder, Dodecene, Trideceth-6, Chlorhexidine digluconate, POloxamer 407, Benzyl salicylate, Benzyl alcohol, Linalool, Isopropyl alcohol, Cetyl esters, Cetrimonium chloride, Butylphenyl methylpropional, Vitis vinifera seed oil, Citronellol, Lauryl PEG, Fragrance. (F.I.L C49322/11)

domain: chemistry


Jockey® Modern Classic V-Neck Shirt 2-Pack
At work under your favorite shirt or at home all on its own, the Jockey® Modern Classic V-Neck Shirt helps you strike the perfect balance between fashionable and comfortable. The finely ribbed 100% cotton fabric has an incredible softness your skin will appreciate, with a form-fitting stretch that follows your every move. The rib knit also adds strength to help keep it looking and feeling the way it should, wash after wash. Now available in a convenient 2 pack.
- Semi-relaxed fit
- 100% Cotton
- Finest quality Fabric
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- Machine Wash at 60°C | Do Not Bleach | Machine Dry | Ironable


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Oct 28 2019 - 4:00pm
Students in need of assistance preparing for the ACT Test are invited to this free weekly event. Students from the National Honor Society of Fayetteville High School will lead tutoring sessions in the Children's Library on Mondays from 4:00pm-6:00pm. Each session will focus on a specific subject... more
Oct 28 2019 - 6:00pm
The Fayetteville Public Library will hold free yoga classes on Monday nights from 6 to 7 p.m. in the Walker Community Room. Classes are taught by a team of volunteer yoga instructors, so the variety of types of yoga done each week will vary. These classes are suitable for all levels of yoga... more
Oct 29 2019 - 9:00am
Would you like to learn more about health and human services available in Northwest Arkansas? Would you like to receive assistance in accessing those services? Come see a Hark Community Liaison Tuesdays from 9am to noon to be connected with assistance in housing, food, education, mental health,... more
Oct 29 2019 - 10:30am
Join us each Tuesday for a storytime featuring themed books, songs, and a craft! This storytime is designed for children ages 3 to 5. Registration is not required.
Oct 29 2019 - 4:00pm
Homework doesn't have to take place in the home! If your child needs additional help with homework assignments, the Homework Helpers program is for you. Children and teens in grades 1st through 9th can receive individual tutoring with a member of the Fayetteville High School National Honor ... more
Oct 29 2019 - 4:30pm
Just in time for the Mexican holiday, Día de los Muertos, Teens in grades 5th-12th are invited to create their own painted skulls known as calaveras. This event is free to teens, and all supplies will be provided. Registration is required for this event and will open on October 8th at 9:00am.
Oct 30 2019 - 10:30am
Join us each Wednesday for a storytime featuring themed books, songs, and a craft! This storytime is designed for children ages 3 to 5. Registration is not required.
Oct 31 2019 - 9:45am
For birth to 24 months. This story time recognizes the developmental needs and attention spans of babies and young toddlers. Parents and Caregivers interact with their babies through a variety of nursery rhymes, action rhymes, songs, and stories. Because Baby Bookworms have short attention spans,... more
Oct 31 2019 - 10:30am
Toddler Time follows a traditional story time format but special care is taken to include opportunities for movement, repetition, and short picture books. Children sit near their caregivers during the story time so that they may interact. The goal of Toddler Time is to develop an early... more
Nov 1 2019 - 3:00pm
Find It, Fund It helps match grantseekers with funders using the Foundation Directory Online Professional database. It is free and open to the public. Registration is required and opens October 11. Can't make the class? Contact us at firstname.lastname@example.org to schedule a consultation.

domain: library


text:
- The Genuine Article: Race, Mass Culture, and American Literary Manhood (New Americanists)
- Join Kobo & start eReading today
- Duke University Press
- Publishing the Family - June Howard - Google книги
The Genuine Article: Race, Mass Culture, and American Literary Manhood (New Americanists)
Though Howard situates her work with reference to social and cultural theorists such as Stuart Hall and Fredric Jameson, where McHenry more often cites historians of reading such as Roger Chartier and Carl Kaestle, both make rich and meticulously historicized discoveries which will fascinate scholars in American literary and cultural studies, while intriguing students of the U. Clarifying the methodological innovations central to Publishing the Family , Howard calls her approach a "microhistory" designed to disclose the many forces and counter-pressures which traverse a collaborative novel entitled The Whole Family.
This anomalous text, which first appeared serially in Harper's Bazar in and , may seem a minor belletristic lark. Yet as Howard shows, no sooner had the second installment of The Whole Family appeared in print than the project was embroiled in contention. Not only did individual contributors--each of whom took responsibility for one chapter of the novel--disagree sharply over the story's premise.
In addition, putative co-laborers found little common ground concerning the nature and motivations of various characters; the genre appropriate to what had been envisioned as a pleasant and amusing, rather than dauntingly conflictual, tale; or a fit ending to the convoluted plot produced by writers located quite differently amidst the literary and social worlds which co-existed at the start of the twentieth century. In and through the resultant tensions, backtrackings and short-lived "resolutions," Howard finds an all-but-articulated critique of white middle-class family life.
- The Dark Side of Liberalism: Elitism vs. Democracy: Elitism Vs.Democracy.
- AWWA standard for dimensions for fabricated steel water pipe fittings;
- Post-Industrial Lives: Roles and Relationships in the 21st Century.
- The Radicant!
- Integrating Human Aspects in Production Management: IFIP TC5 / WG5.7 Proceedings of the International Conference on Human Aspects in Production Management 5–9 October 2003, Karlsruhe, Germany;
- e-book Publishing the Family (New Americanists)!
The utter lucidity of Howard's argument should serve as a model for future work of interdisciplinary amplitude. Yet range of research interests is only one reason to categorize Publishing the Family as a scholarly tour de force. Equally important, this probing, fearless study deserves the attention of all students of sentimentality and affectional acts, even as it takes up a prominent place in the toolbox of those who investigate the conditions of literary and ideological production.
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People trained in American Studies do not always spend time ruminating about management strategies at the best-known publishing firms, or about the relationship between a "house organ" like the Bazar and its parent company. Yet as Howard shows, these things can be tremendously revealing not so much because the business of America is, as we hear so often, business, as because print culture exists under specific conditions of capital which, in the case of The Whole Family , tangled with competing visions of domesticity, trade, women's education, and modernity.
The profoundly eruptive ramifications of Publishing the Family can be derived from Howard's brilliant introduction. This finding should stand as a key--and crucially periodizing--model for those students of culture who seek ways in which to figure out what print culture has to tell us about the era in which it was produced, rather than the anxieties of our own. Beautifully illustrated and written with unusual grace, Publishing the Family is a book that students of U. Closer to the heart of historical reading studies, but as challenging to received parameters as Howard's elegant argument, Elizabeth McHenry's Forgotten Readers demands that attention be paid to the small, but united and purposeful, group of pre-World War II African Americans who equated literacy with activism.
Central to McHenry's initiative is a deliberate and well-defended extension of exclusivist conceptualizations of what it has meant to participate in the world of print and, more specifically, belles lettres. Indeed, one of the major gains of her project is enhanced comprehension of the goals of those "race" men and women who taught that the assured wielding of elevated language comprised a form of political agitation.
This form of agitation may seem trivial.
Duke University Press
Yet it proved capable of nurturing solidarities among people who were socially marginalized by white supremacist policies, fostering "uplift" programs with strong links to citizenship claims, and resisting the dictum that informal education was tantamount to ignorance and illiteracy. Challenging assumptions about African Americans' practices and institutions of reading, writing, and educated debate, McHenry sheds new light on texts as familiar as David Walker's "Appeal" and Jean Toomer's Cane.
This reconfiguration echoes Howard's call for a testing of current taxonomies, the better to work out more illuminating insights. Yet for McHenry, the goal is reconsideration of "what has constituted resistance for African Americans given their diverse experiences" p. Each chapter of Publishing the Family casts light on some aspect of life in the United States at a moment that arguably marked the beginning of our own era.
Howard revises common views of the turn-of-the-century literary marketplace and discusses the perceived crisis in the family as well as the popular and expert discourses that emerged to remedy it.
Publishing the Family will interest students and scholars of American history, literature, and culture, as well as those studying gender, sexuality, and the family. In the process, she uses the phenomenon of this collaboratively authored novel to subject our commonsense assumptions about literary creativity to searching scrutiny. Valuable not only for its impressive scholarship but also for its originality and insight, Publishing the Family is sure to occupy a prominent place in American literary and cultural studies.
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Publishing the Family - June Howard - Google книги
If a book exceeds Shipping costs are based on books weighing 2. A House Undivided. A Climb up the Spiral Staircase. Everybodys Busy Day. The Composite Novel as Vaudeville. Female Modernity and the Magazine. What Is Sentimentality? Embodied Thoughts. Feeling and Form.


text: Animal proteins and fats are important and sustainable components of animal feed for livestock. In the EU, the partial lift of the feed-ban is opening a great perspective for the feed sector. Sinova produces ingredients for the animal feed industry that are safe and highly digestible. With transparent, sustainable and safe supply chains and manufacturing processes, we are able to address the needs of our customers in the animal feed sector and contribute to healthy and efficient nutrition for livestock. The feed industry today faces a multitude of challenges: globalised markets, short delivery capabilities and high expectations in terms of sustainability to name just a few… Sinova guarantees a secure and regular supply while at the same time contributing to the reduction of the carbon footprint. Our products increase the efficiency and success of the feed industry while simultaneously increasing the well-being and nutritional intake of animals.

domain: agronomy


text:
The Central African Republic (CAR), located in Central Africa, continues to grapple with persistent violence due to the presence of various rebel groups and criminal gangs. A recent tragic event spotlighted this precarious situation: on December 21, 2023, the village of Nzakoundou witnessed a deadly attack attributed to the 3R (Return, Reclamation, and Rehabilitation) armed group, resulting in the deaths of 23 civilians.
In response to this massacre, the United Nations (UN) acted swiftly. The UN’s mission in CAR, known as MINUSCA, deployed peacekeeping troops to the region with the objective of enhancing security and facilitating humanitarian access to the traumatized population. However, despite these efforts, the situation remains volatile and intricate.
The 3R group is just one of the many players in this complex landscape. CAR faces a myriad of rebel groups and criminal gangs that terrorize civilians and destabilize the nation. Some of these groups, such as the Coalition of Patriots for Change (CPC), even attempted to overthrow President Faustin Archange Touadéra’s government in December 2020.
Furthermore, the involvement of private security forces, notably Russian allies described as “mercenaries” by the UN, introduces an additional layer to this crisis. These forces, along with CAR’s military and armed groups, face accusations from the UN and international NGOs of committing crimes and atrocities against civilian populations.
In light of these challenges, the people of CAR express their outrage and demand justice. Opposition political parties, like the URCA, urge authorities to implement concrete measures to support victims, rebuild destroyed villages, and ensure the safety of civilians.
However, the Central African Republic remains embroiled in significant security challenges. The UN’s intervention is pivotal, but a comprehensive approach involving regional stakeholders is essential to address the root causes of the conflict and pave the way for lasting peace and stability.
Written by Imane MoumenShare this:

domain: sociology


text:
If you wish to redeem your auto loan and keep your car in Chapter 7 bankruptcy the requirement is to pay the replacement value for your car. The same holds true for a loan for your truck, boat, or motorcycle. Additionally, mobile homes not attached or affixed to the land are also redeemable.
Again, redemption is only allowable in Chapter 7 bankruptcy, and officially you must offer a replacement (retail value). Also, sometimes they offer trade-in values using NADA or KBB. However, only personal property is redeemable.
Chapter 7 Bankruptcy • Auto Loan Redemption
In Chapter 13 you might be able to “cram down” the auto loan, which is similar to a redemption. You can only “cram down” the car loan in Chapter 13 if the purchase date is more than 910 days ago, you use it commercially, or in Kentucky, if the car loan was refinanced.
When you file Chapter 7 bankruptcy in Kentucky, please take the time to consider think whether or not you want the following to take place:
- Surrender your car, and owe nothing. This is a clear choice if the car is a lemon.
- Reaffirm your car with the bank, through the court, and continue to pay the bank the same payments. This option is only available if you owe less than the auto is worth.
A reaffirmation in Chapter 7 bankruptcy court is a good choice if the following criteria are met:
- You owe less than the wholesale price of the car.
- The interest rate is good.
- You are on good terms with the lender. If you are on poor terms with the lender they might reaffirm and then, repossess the car after your bankruptcy is over and sue you for the deficiency.
Alternatively, you can sometimes redeem your car and buy it from the bank by filing a motion with the court under Chapter 7 for the replacement value. This option is only available for you to owe more than the car is worth.
Bottom line: if you are paying too much for your car you should file a redemption or surrender it. A company named 722 redemptions will often finance it if you don’t have the cash to do the redemption. 722 Redemption saves the average customer $8,000. (Call 722 Redemption at: 1-888-721-2800). You can keep the personal property for replacement value such as cars, boats, and mobile homes.
Resources for Bankruptcy
Other Related Information
If you are thinking about filing bankruptcy, don’t delay because timing is crucial. I am here to help you. So, contact my office right away to start the conversation. Nick C. Thompson, Bankruptcy Lawyer: 502-625-0905


text: [Iraq boots-on-the-ground report] FIREFLY: Banking news today on Channel One for the first time ever they’re telling us our bank in Iraq have recorded assets over 200 trillion dollars. News says accounts are up all over the place. FRANK: I kept telling you, you have no idea how much they have to back up their currency. That’s just assets. You also have futures in the ground, contracts that have been signed, supply and demand of the basket…I get the chills thinking about the power of this nation.

domain: news


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Who We Are
To improve vulnerable women's means of subsistence and access to high-quality healthcare while also eradicating all forms of discrimination and gender-based violence.
A prosperous and discrimination-free Rwanda.
What is FADA?
FADA (Feminist Action Development Ambition) is a feminist organization founded in 2015 with an aim to contribute towards the promotion and protection of women’s rights, especially the most vulnerable and disadvantaged groups.
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Friday, December 7, 2007
foot and mouth disease
My usual route into Colombo for my weekly sales and deliveries results in my passing the parliament road that circumvents the National Assembly that is housed in a man made island in the middle of Diyawanna Oya. Owing to the budget debates now going on, the road is closed to my vehicle which comes under the category of a heavy goods vehicle. This means that I have to double back and get into more traffic, which delays my journey more than I would like.
I was commenting today, that parliamentarians on both sides, if one reads what is being said in the press, are in a jostling match amongst each other with very little regard to the needs, concerns and aspirations of the electors who put them there. It is either a slanging match on who can shout the loudest. Those who are actually doing much of the talking are full of themselves and not much else. It is like 'Nero is talking to the gods about all the good he is doing while Rome burns' kind of situation.
The comedy is further exacerbated because the police who are busy on all the approach roads, act as if each convoy that comes brings the president, as they are not told who the vip is on their way in. As there are over 100 ministers, the police give the same servile treatment to all and the Johnny come lately who is on his way to parliament is chaffed at the royal treatment meted out at the expense of the exasperated and long suffering motorist.
What is said and expounded on the floor of the house matters to no one, as what is said is meaningless, listened to by hardly anyone and reported only if the level of comedy rises to new highs. The results of the votes bear no relation to what is said in there.
I liken it to a foot and mouth disease that our lawmakers have, who are oblivious to the plight of the people they represent. Parliament consists just of yes men obeying their leaders with few who have the guts to come clean and talk sense. There is hardly anyone without dirt sticking to them. Even the muddied paddy farmer being visually cleaner than them.
The public are apathetic to protest or are in fear of protesting at these antics, for being incorrectly branded by the most corrupt as being unpatriotic. This is something to be concerned about.
Does no one see this drama for what it is and do something about it? or are we forever to be consigned to the scrap heap of history? We will be branded as a spineless populace with no backbone that allowed our lawmakers to ride roughshod over this land, and permanently disfigure its core.Lets not at all worry what others think of us, and only care about what they have done to the people living here, and the pathetic example they have shown.
This sums up parliamentary democracy Sri Lanka style. Keep the foot in the mouth and we will really be OK.

domain: politics


Plaxico Burress will have the chance to do what he recently talked about: try for Super Bowls on both New York teams.
More importantly, the Jets have given the 33-year-old receiver a second chance at the NFL, after serving nearly two years in prison for gun possession.
Burress and the Jets agreed to terms on a deal this morning, the team confirmed. ESPN first reported the move, reportedly a 1-year deal for $3.017 million fully guaranteed.
“I know they have a good team and everybody knows Rex (Ryan), so …” Burress told The Star-Ledger on Saturday, when asked about the Jets. “I think (Ryan) is great. He stands behind his players, I think his players have a lot of respect for him and they play hard for him. … He’s a great coach, great personality. He seems like he’s always upbeat.”
Burress said Saturday he had been invited to visit the Jets but wasn't sure whether or not he would go. As of last night, he was not expected at the team facility today. He visited the Giants Friday and the Steelers Saturday, and was expected to meet with the 49ers as well.
The Jets lost out on the Nnamdi Asomugha sweepstakes Friday but have still found a way to make a big splash in free agency.
Burress wrote on his Twitter account, "East Coast here I come!" Quarterback Mark Sanchez welcomed Burress to the team also via Twitter.
The addition of Burress, who is 6-foot-5 and a uniquely talented player before his prison time, indicates the Jets will not re-sign fellow receiver Braylon Edwards, despite his desire to return to the team.
Burress will be teamed with Santonio Holmes, also a former Steeler, and Jerricho Cotchery. The Jets and Giants play at New Meadowlands Stadium Christmas Eve.


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A nursery, like any other retail business, calls for regular restocking. Perhaps this is a chore for other business owners, but I must confess that my regular expeditions to stock up on plants are one of my favourite parts of the job.
To start with, there is the pleasure of getting out of town and driving through the lovely countryside where most of my sources are located. The fun of sharing trade secrets and gardening gossip with plant suppliers is followed by the supreme satisfaction that only retail therapy can bring. Then there is the leisurely drive home with jolly flower heads bobbing in my rearview mirror and perhaps a gorgeous perfume filling the car. And if a friend comes along for the ride, the three or four hours of uninterrupted conversation are the cherry on the top. The irritated, world weary faces of the drivers around me as I head back into town just add to how blessed I feel to be doing what I do!
IN THE GARDEN
In spite of the heat which it seems we must accept as the new normal, the garden is positively overgrown and in need of our regular light mid-summer prune.
We have had some rain which is always welcome but I have actually realised that apart from the hydrangeas, most of our plants seem to need far less water than one would think. We water mainly to cool down the beds – and the house! This is surprising if you consider that with our garden serving as an experimental space we don’t necessarily focus on introducing water wise plants.
For those of you who are looking for ways to drought proof your gardens however, Tanya Visser shared some interesting tips in a recent episode of “The Gardener” on DSTV’s Home Channel on how to identify plants that are drought and heat resistant. Apart from the obvious plants with fleshy leaves, you should also look out for hairy leaves, grey or silver leaves and, believe it or not, square stems! More erudite readers will know what the scientific reasons are for this but I can say that Tanya’s advice definitely confirms my experience with plants like salvias, helichrysum and even some plectranthus.
IN THE NURSERY
You can now view all the plants listed in this newsletter on one page on the website.
· Indigenous plants
Barleria greenii is a rare rounded 1 m high shrub with shiny dark green leaves and night scented open pink flowers from summer to autumn. Evergreen and very hardy, it grows in sun or semi shade and likes clay soil.
The small form of the interesting deciduous bulb Eucomis zambesiaca reaches a height of about 25 cm and has attractive broad strap like leaves and small green flower spikes with bracts of white flowers in summer. It is hardy and likes full sun. A good cut flower.
The gorgeous wavy edged red and yellow flowers of the aptly named Gloriosa superba are also good for the vase. A hardy deciduous scrambling bulb with huge tubers and shiny tapered bright green leaves, it likes semi shade and grows about 2 m high.
Lessertia frutescens is a short lived but self-seeding shrub known for its miracle medicinal properties. Evergreen and very hardy, it has pinnate silver leaves and bright orange flowers from spring to summer followed by bladder like seedpods. It likes full sun and dry sandy soil.
· Exotic plants
Aster nova belgii “Jenny is a low growing (30 cm high) mound forming perennial with pretty yellow centred lilac flowers from summer to autumn. Evergreen and very hardy, it likes full sun.
A tough evergreen twining African climber, Dolichos purpureus reaches a height of about 2.5 m. It has large purple backed leaves and lilac flowers from spring to summer. The more adventurous might like to try the edible beans. Eat them when they are still green; they are not very palatable once they have turned purple!
Ruellia macrantha is a 75 cm high soft stemmed perennial with bright green lance shaped leaves and showy rose pink flowers from autumn to winter. It is semi hardy and evergreen and likes semi shade. It can possibly be grown indoors but I have yet to investigate this.
You might know the interesting deciduous climber Vigna Caracalla as the snail vine, a name which comes from its clusters of scented snail like flowers which start off yellow and fade to lavender. This is a hardy plant which grows to a height of 5 m and flowers from summer to autumn. It can take sun or semi shade but don’t plant it near foundations – it has a huge root ball.
If you have never visited SANBI's PlantZAfrica website do yourself a favour. It is a veritable treasure trove of information for anyone with a special interest in the plants of southern Africa.
Only a few more weeks of extreme heat and then we can look forward to the wonderful mild days of autumn. In the meantime, stay hydrated and...

domain: biology