KENILWORTH, N.J. – Aug. 30, 2018 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved two new HIV-1 medicines: DELSTRIGO™, a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg); and PIFELTRO™ (doravirine, 100 mg), a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be administered in combination with other antiretroviral medicines. Both DELSTRIGO and PIFELTRO are indicated for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience, and are administered orally once daily with or without food. DELSTRIGO contains a boxed warning regarding post-treatment acute exacerbation of hepatitis B (HBV) infection. DELSTRIGO and PIFELTRO do not cure HIV-1 infection or AIDS.
DELSTRIGO and PIFELTRO are contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to 3TC. For more information, see "Selected Safety Information" below.
Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent, as cases of acute renal failure after initiation of high -dose or multiple non- steroidal anti-inflammatory drugs (NSAIDs) have been reported in patients with risk factors for renal dysfunction who appeared stable on TDF.
The FDA approvals of DELSTRIGO, the once-daily fixed-dose combination tablet as a complete regimen, and PIFELTRO, a new NNRTI, are based on findings from the pivotal, randomized, multicenter, double-blind, active controlled Phase 3 trials, DRIVE-AHEAD and DRIVE-FORWARD, evaluating the efficacy and safety of DELSTRIGO and PIFELTRO, respectively, in participants infected with HIV-1 with no antiretroviral treatment history.
In DRIVE-AHEAD, 728 participants with no antiretroviral treatment history were randomized and received at least one dose of either DELSTRIGO or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV 600 mg/FTC 200 mg/TDF 300 mg) once daily. DELSTRIGO demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non-inferior efficacy compared to EFV/FTC/TDF (84% in the DELSTRIGO group achieved viral suppression of HIV-1 RNA <50 copies/mL vs. 81% in the EFV/FTC/TDF group; treatment difference: 3.5%, [95% CI:] -2.0%, 9.0%). Of the 21 percent of study participants with a high viral load at baseline (HIV-1 RNA >100,000 copies/mL), 77 percent in the DELSTRIGO group and 72 percent in the EFV/FTC/TDF group achieved HIV-1 RNA <50 copies/mL at Week 48.
At Week 48, DELSTRIGO-treated participants showed statistically significant superior lipid profiles as measured by changes from baseline in LDL-cholesterol and non-HDL- cholesterol (LDL-C: -2.1 mg/dL in the DELSTRIGO group vs. 8.3 mg/dL in the EFV/FTC/TDF group; treatment difference: -10.2 mg/dL, [95% CI:] -13.8, -6.7, p<0.0001; non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs. 12.7 mg/dL in EFV/FTC/TDF; treatment difference: -16.9 mg/dL, [95% CI:] -20.8, -13.0, p<0.0001). However, the clinical benefit of these findings has not been demonstrated. In addition, a statistically significant lower proportion of DELSTRIGO- treated participants compared to EFV/FTC/TDF-treated participants reported neuropsychiatric adverse events in the three pre-specified categories of dizziness (9% vs. 37%; treatment difference: -28.3%, [95% CI:] -34.0, -22.5, p <0.001), sleep disorders and disturbances (12% vs. 26%; treatment difference: -13.5%, [95% CI:] -19.1, -7.9, p <0.001), and altered sensorium (4% vs. 8%; treatment difference: -3.8%, [95% CI:] -7.6, -0.3, p=0.033).
The rate of discontinuation of treatment due to adverse events was lower in the DELSTRIGO treatment group than in the EFV/FTC/TDF treatment group (3% and 6%, respectively). Clinical adverse reactions of all grades occurring in ≥5 percent of participants in the DELSTRIGO treatment group included dizziness (7%), nausea (5%) and abnormal dreams (5%). No adverse reactions of Grade 2 or higher (moderate or severe) occurred in ≥2 percent of participants treated with DELSTRIGO.
In DRIVE-FORWARD, 766 participants with no antiretroviral treatment history were randomized and received at least one dose of either PIFELTRO once daily or darunavir 800 mg + ritonavir 100 mg (DRV+r) once daily, each in combination with emtricitabine (FTC)/TDF or abacavir (ABC)/3TC selected by the investigator. PIFELTRO demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non -inferior efficacy compared to DRV+r, each in combination with FTC/TDF or ABC/3TC (84 % in the PIFELTRO group achieved viral suppression of HIV-1 RNA <50 copies/mL vs. 80% in the DRV+r group; treatment difference: 3.9%, [95% CI:] -1.6%, 9.4%). Of the 20 percent of study participants with a high viral load at baseline (HIV-1 RNA >100,000 copies/mL), 77 percent in the PIFELTRO group and 74 percent in the DRV+r group achieved HIV-1 RNA <50 copies/mL at Week 48.
At Week 48, PIFELTRO-treated participants showed statistically significant superior lipid profiles as measured by changes from baseline in LDL-cholesterol and non-HDL-cholesterol (LDL-C: -4.6 mg/dL in the PIFELTRO group vs. 9.5 mg/dL in the DRV+r group; treatment difference: -14.4 mg/dL, [95% CI:] -18.0, -10.8, p<0.0001; non-HDL-C: -5.4 mg/DL in the PIFELTRO group vs. 13.7 mg/dL in the DRV+r group, treatment difference: -19.4 mg/dL, [95% CI:] -23.4, -15.4, p<0.0001). However, the clinical benefit of these findings has not been demonstrated.
The rate of discontinuation of therapy due to adverse events in either treatment group was low (2% in the PIFELTRO group and 3% in the DRV+r group). Clinical adverse reactions of all grades occurring in ≥5 percent of participants in the PIFELTRO treatment group included nausea (7%), headache (6%), fatigue (6%), diarrhea (5%) and abdominal pain (5%). No adverse reactions of Grade 2 or higher (moderate or severe) occurred in ≥2 percent of participants treated with PIFELTRO.
DELSTRIGO and PIFELTRO can be co-administered with a wide range of non-antiretroviral agents, and PIFELTRO can be co-administered with a wide range of antiretroviral agents. DELSTRIGO and PIFELTRO cannot be co-administered with enzalutamide, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, rifapentine, mitotane or St. John's wort. If DELSTRIGO is co-administered with rifabutin, patients should take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is co-administered with rifabutin, patients need to increase the PIFELTRO dosage to one tablet twice daily approximately 12 hours apart. Use of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended.
No clinically significant changes in concentration have been observed following the co- administration of doravirine and the following drugs: dolutegravir, ritonavir, TDF, 3TC, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, atorvastatin, an oral contraceptive containing ethinyl estradiol and levonorgestrel, metformin, methadone, and midazolam. For DELSTRIGO, no clinically significant drug interactions have been observed in studies conducted in healthy participants between TDF and the following medications: entecavir, methadone, oral contraceptives, sofosbuvir or tacrolimus. If DELSTRIGO is co-administered with ledipasvir/sofosbuvir or sofosbuvir/velpatasvir, monitor for adverse reactions associated with TDF. Co-administration of single doses of 3TC and sorbitol resulted in a sorbitol dose- dependent reduction in 3TC exposures. When possible, avoid use of sorbitol-containing medicines with 3TC-containing medicines, such as DELSTRIGO.
In the DELSTRIGO and PIFELTRO treatment arms of the DRIVE-AHEAD and DRIVE- FORWARD trials (n=747), a total of 11 participants showed the emergence of doravirine- associated resistance substitutions, among the 28 participants in the resistance analysis subset (participants with HIV-1 RNA >400 copies per mL at virologic failure or early study discontinuation and having resistance data). Of these 11 participants, seven showed both genotypic and phenotypic resistance to doravirine, with at least a 100 -fold reduction in susceptibility to doravirine. The other four participants had substitutions that were associated with less than twofold reduction in susceptibility to doravirine.
In the EFV/FTC/TDF treatment arm of the DRIVE-AHEAD trial (n=364), 12 participants showed the emergence of efavirenz-associated resistance substitutions among 20 participants in the resistance analysis subset. In the DRV+r treatment arm of the DRIVE-FORWARD trial (n=383), no participants showed the emergence of DRV+r associated resistance substitutions among the nine participants with resistance data.
Cross-resistance has been observed among NNRTIs, including doravirine. Treatment- emergent doravirine resistance-associated substitutions can confer cross-resistance to efavirenz, rilpivirine, nevirapine and etravirine. No significant cross-resistance has been demonstrated between doravirine-resistant HIV-1 variants and 3TC, FTC or tenofovir or between 3TC or tenofovir-resistant variants and doravirine.
The approvals of DELSTRIGO and PIFELTRO come ahead of the original FDA target action date of Oct. 23, 2018. Merck anticipates that PIFELTRO and DELSTRIGO will be stocked through wholesalers within one month. Merck is working to obtain access for patients in government-sponsored programs, including Medicare Part D, Medicaid and AIDS Drug Assistance Programs. Upon approval, DELSTRIGO and PIFELTRO will be covered products under the Merck Patient Assistance Program and will be available to eligible patients when the medicines are available. Doravirine is also under regulatory review by the European Medicines Agency (EMA).
All patients with HIV-1 should be tested for the presence of HBV before initiating antiretroviral therapy. Severe acute exacerbations of HBV have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing lamivudine or TDF, which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti -HBV therapy may be warranted.
In clinical trials in HIV-1 infected adults, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 vitamin D levels were also higher.
Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF.
There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263. Mothers infected with HIV-1 should be instructed not to breastfeed if they are r eceiving DELSTRIGO due to the potential for HIV-1 transmission. Because DELSTRIGO is a fixed-dose combination tablet and the components cannot be altered, it is not recommended in patients with estimated creatinine clearance less than 50 mL/min.
PIFELTRO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John's wort (Hypericum perforatum)), as significant decreases in PIFELTRO plasma concentrations may occur, which may decrease the effectiveness of PIFELTRO. Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Co- administration of PIFELTRO with efavirenz, etravirine or nevirapine is not recommended. If co- administered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart).
Consult the full Prescribing Information prior to and during treatment for important potential drug-drug interactions. The safety of PIFELTRO is based on two studies, DRIVE-FORWARD and DRIVE-AHEAD. In DRIVE-FORWARD, the most common adverse reactions (incidence ≥5%, all intensities) were nausea (7%), headache (6%), fatigue (6%), diarrhea (5%) and abdominal pain (5%). In DRIVE-AHEAD, the most common adverse reactions (incidence ≥5%, all intensities) were dizziness (7%), abnormal dreams (5%) and nausea (5%) .
There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263. Mothers infected with HIV-1 should be instructed not to breastfeed if they are receiving PIFELTRO due to the potential for HIV transmission.
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far -reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer's disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward -looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delay s; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's 2017 Annual Report on Form 10 -K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).


New Delhi: The results of SBI Junior Associate (JA) Clerk Preliminary examination 2018 (SBI Clerk Prelim exams 2018) are likely to be released today by State Bank of India (SBI).
Although no official statement has been given by the SBI, information available on various portals suggests that the SBI Clerk Prelim exam 2018 results is going to be released on or before 28 July. So all the candidates are advised to keep a watch on the official website of SBI as results likely to be out soon.
• Fill in your details and submit it by clicking on 'OK' tab.
• Your results will appear on the page.
• Download your result of SBI Clerk prelims exams and print a copy of it.
The SBI Clerk Prelim 2018 were held on June 23, 24 and 30, 2018. The exams were conducted by SBI bank to fill in 8,301 vacancies of for the vacant posts of SBI junior associate. After the release of results, candidates who qualify the SBI JA Clerk Prelim will be eligible to appear for SBI JA Main examinations 2018, which will be held on August 5, 2018. The call letter or admit card for SBI JA Main examinations 2018 will be released by July end.


The World Health Organization has reported that the incidence of melanoma is increasing faster than that of any other cancer in the world.
The World Health Organization has reported that the incidence of melanoma is increasing faster than that of any other cancer in the world. Melanoma occurs when melanocytes – melanin-producing cells – become malignant. Malignancy of melanocytes in the basal layer of the skin is referred to as primary cutaneous malignant melanoma. Unlike many other common cancers, there is no significant increase in risk for the elderly; instead, the increase in incidence is likely to be due to changes in lifestyle. In particular, the amount of and susceptibility to ultraviolet exposure are key risk factors for malignant melanoma, and are driving the increase in incidence in all age groups.
The melanoma market is projected to reach $7.8bn in value by 2026, with growth driven by immune checkpoint inhibitors.
The introduction of targeted therapies has substantially changed the treatment landscape of melanoma.
Melanoma is a common cancer in the Western world with an increasing incidence, although prognosis is highly variable.
Immune checkpoint inhibitors will continue to dominate the market through new drug combinations and label expansions.
Drug development will consist predominately of novel immune checkpoint inhibitor and MAPK inhibitor combinations.


This class handles an EAV definition attached to a \Dewdrop\Db\Table object. The EAV definition can load and save values for an EAV field, retrieve the list of available attributes, optionally filtered (e.g.
to a single user account's attribute), etc.
You can modify the "_eavvalues" portion of the value table names by changing the $valueTablePrefix property.
If you'd like to just stick with the Dewdrop naming conventions, you can generate the EAV tables using the "gen-eav" CLI command.
The Table object this EAV definition is associated with.
The name of the table where EAV attributes are stored. Defaults to the name of the table that this EAV definition was registered to with a suffix of "_attributes".
The prefix that will be used for value table names. The value table's full name is composed of the name of the table that registered this EAV definition, then this prefix, and then the backend type of the attribute that is being saved.
The available attributes for this EAV definition. This is lazy-loaded the first time you attempt to call any attribute related method.
The index in the attribute definition that determines whether the field is required.
The name of a column in the attributes DB table that will be true when the attribute should be treated as if it was deleted.
Register a new EAV definition to supplied table and set any additional options specified in the supplied array.
Set multiple options using the supplied array of option name and value pairs.
Set the name of the table where you want to store attributes (not values, but the actual rules/metadata for the attribute itself) for this EAV definition.
Set the prefix that will come before the backend type in a value table's name.
Set a callback for filtering the initial \Dewdrop\Db\Select object that retrieves the list of available attributes. This can be any valid PHP callable (i.e. function name as string, anonymous function, or method array). The function should return the modified \Dewdrop\Db\Select.
Get the name of the table where attributes are stored. If none is set, we use the name of the table this EAV definition is registered to followed by "_attributes".
Check to if there is an attribute with the supplied name.
Set the index of the column in the attributes table that will be used to determine if an attribute is required or not. Useful if you require an attribute in some contexts but not others (e.g. you have a column called "is_required_public" and another called "is_required_admin" and need to consult a different column depending upon who is logged in).
Get the index/name of the column in the attribute definition that tells us if a value is required.
Set the index of the column in the attributes table that will be used to determine if an attribute has been deleted or not. Useful when end-users can delete attributes via some kind of GUI.
Get a \Dewdrop\Db\Adapter::describeTable() compatible metadata definition.
This allows EAV field's to integrate nicely with the standard Field API.
Get the full set of attributes supported by this definition. The array's keys are the attribute field names (e.g. "eav_1" or "eav_22") and the values are the information from the attributes table in the DB.
Get information about the attribute matching the supplied name.
Save the value for the supplied attribute, using the primary key values from the table this EAV definition is registered to.
Load the initial value for the supplied attribute name. If the supplied row is new (i.e. no primary key value), then we use the default value for the attribute. Otherwise, we query that appropriate value table.
Augment the provided Select object with all the EAV attribute values from this definition.
Assemble the name of the value table for the supplied backend type.
Load the list of available attributes from the database, if they haven't been loaded already. The array of attributes will use the attribute field name (e.g. "eav_1") for a key.
Determine a generic data type appropriate for the supplied EAV type.
The EAV backend value tables are named after the data types in the DB, so they don't directly match generic types from our PHP API. This method maps the two domains together so that we can check an EAV field's generic type in our application code.


City leaders in Atlanta found themselves under fire for their response to a major ice storm that swept across southern states and left many thousands, including numerous schoolkids, stranded overnight. As forecasters point out, it's not like they didn't know it was coming.
From my vantage point in Miami (86F today) I take a look at the big chill, the second in weeks, covering most of the rest of the country. Days like these make me glad to be in sub-tropical South Florida!
Jacqui took a look at a coming attraction at Universal Studios in Orlando. Harry Potter fans rejoice!
As a Muggle, I shouldn't be able to see Diagon Alley, the fictional London street accessible only to wizards and witches — yet here I am, standing in its midst, gazing at the impressive white façade that is Gringotts Bank.
This summer, fellow Muggles — the name given to non-magical folk — will also be able to walk down this scene straight out of JK Rowling's Harry Potter books.
For now, on my sneak preview of Universal Studios' newest Wizarding World of Harry Potter attraction in Orlando, parts of the alley and its sinister side street, Knockturn Alley, are still under scaffold. Cranes tower overhead, there is sand underfoot instead of Victorian-style cobblestones, and workers in hard hats and neon vests move in and out of partially furnished buildings carrying tools, buckets and materials. Yet emerging from this disorder is an attraction impressive in its scale, its layers of detail and its fidelity to the mystical world of Rowling's original vision. There are leaning, twisting, two and three-storey shop fronts, gas lamps ready to flicker into life, a train trestle running overhead, signs advertising magic wands, and even a jellied eel shop.
Equal in area to the existing Harry Potter attraction — which features Hogwarts Castle and the fictitious Scottish village of Hogsmeade — Diagon Alley has involved thousands of designers, artisans, technicians and engineers, and is the company's most ambitious and complex endeavour to date.
The big ride — Harry Potter and the Escape from Gringotts — will be inside the wizards' bank, where scores of goblins, created by technical jiggery-pokery, will be hard at work. As they push deeper underground, visitors will see metal carts carrying gold ingots, dusky stone walls dripping with slime, and stalactites and stalagmites. Further details remain secret, although the ride is likely to follow the storyline in Harry Potter and the Philosopher's Stone, in which the boy wizard and his friends break in to Gringotts' vault to steal from the evil Lord Voldemort, then flee on a dragon. A giant, fire-breathing animated dragon will be perched atop the building.
The ride's creators promise that it will surpass even Harry Potter and the Forbidden Journey, the existing Wizarding World ride. "Escape from Gringotts is so elaborate and so big — it's an unprecedented scale of experience," says Mark Woodbury, president of Universal Creative.
Linking Hogsmeade and Diagon Alley will be the Hogwarts Express, the iconic red steam train on which Potter and friends chug back and forth from London to Scotland. Instead of seeing Universal rollercoasters and back-lots through the windows, special effects will give passengers a view of the rolling English countryside and Scottish Highlands.
The train's construction needed multiple research trips to Britain — "the ultimate trainspotters' outing", jokes Alan Gilmore, the art director behind the Potter movies and Wizarding World. Sculptors flew to London to gaze at and prod old brickwork so they could recreate its exact size, texture and pigment. Architects were sent to study King's Cross station, Charing Cross Road, Leicester Square Tube station and Wyndham's Theatre, which collectively make up the façade through which guests will pass from the Muggle world into the wizarding world by secretive means yet to be divulged.
How one glides through the brickwork of King's Cross to board the Hogwarts Express on Platform 9¾ — as Potter and friends do — is also under wraps, but Matthew Lewis, who played Neville Longbottom in the films, says it will be so unique that it will "blow people away". The eerie, three-deck Knight Bus will also feature. Guests will not be transported on it, but will have the opportunity to interact — including with the loquacious shrunken head that lives aboard.
Rowling, for whom Harry Potter has earned a multimillion-pound fortune, was consulted closely throughout, says Dale Mason, the executive art director for Wizarding World: "She helped us name shops and places that don't exist in any of her books but now exist here in her world" — places such as Carket Market and a cross-street she christened Horizonte Alley.
Visitors with cash to spare after paying for the two-park entry ticket can spend it at the Leaky Cauldron pub, where the menu will include fish and chips and bangers and mash; or in Florean Fortescue's Ice Cream Parlour, where frozen delicacies include strawberry-and-peanut-butter flavour. There are also stores ranging from Weasleys' Wizard Wheezes — the joke shop run by Fred Weasley and his twin brother George — to Magical Menagerie, offering cuddly toys such as owls and hippogriffs.
Construction of the Cabana Bay Beach Resort, an 1,800-room budget hotel with a 1950s and 1960s retro theme, where rooms for up to six people cost from only $119, will help to handle the influx of guests that Diagon Alley is expected to generate.
On a mock-up of the Thames Embankment outside Diagon Alley, pieces of a fountain that will house the Statue of Eros, as seen at Piccadilly Circus, lie on the ground waiting to be assembled — one more piece in a jigsaw whose end result promises to look spectacular.
Virgin Holidays (0844 5573859, virginholidays.co.uk) has seven nights in Orlando, room only, at the Cabana Bay Beach Resort, with car hire and flights, from £903pp. Prices at Universal Studios are from £117 for a two-park bonus ticket for 14 days (universalorlando.com).
No good ever comes of cocaine use. Especially when you're a politician that once voted for the mandatory drugs testing of food stamp recipients.
The Telegraph's brave new world?
During my 11 years as a staff journalist at The Daily Telegraph, a period which ended in 2001 with voluntary redundancy just as newspapers were beginning the first wave of the seemingly endless cutbacks that have acted as a wrecking ball to the industry, I lost count of the numerous relaunches, new directions, new initiatives and complete overhauls announced by the company during mass gatherings of staff. Each one promised a bright new future, and yet, more than a decade later, it seems they're still searching for the right formula. There's little doubt that a digital-only future is inevitable, but I remain to be convinced that sacking a popular editor renowned as a journalist's journalist, and giving free rein to a "chief content officer" with next to no experience of national newspapers will provide the bright new dawn they crave. We shall see.
Here's Roy Greenslade's take on things in Thursday's Guardian.
Congratulations to our good friend and Jacqui's former deputy at the Express Tim Shipman, who has just been named political editor of The Sunday Times. He's a wonderful journalist and we're sure he'll excel in his new role.
How a confrontation in a Florida cinema between a retired cop and a man texting on his mobile phone turned deadly. There are no winners here, a 71-year-old possibly heading to jail for the rest of his life.


Hello Trucking Nation, and Merry Christmas from everyone here at Truck Services of North America. We hope you're having a great holiday season so far, whether you're on the road working hard, or just relaxing at the house with some friends and family.
Without you truckers, this holiday wouldn't be possible. No Christmas trees, no turkey dinners, and NO PRESENTS. That's right, we have you all to thank for all the wonderful presents nestled under our trees this Christmas. And who doesn't like presents?
But that's enough of the mushy stuff—back to the fun. Don't forget that with the end of the year, in addition to all the New Year's festivities, comes several trucking renewal deadlines.
The deadline for renewing your UCR registration is December 31, so you'll need to have that done before the end of the year. We understand (probably better than anyone because of what we do) just how difficult and time consuming this process actually is. So if you need help or want someone to take care of this pesky registration for you, then you know who to call. No not Ghostbusters—us!
We know, we know, it seems like the third quarter just ended, right? Well just as soon as it began, it is now officially coming to a close on December 31. So you all should know the drill by now. The quarter is ending, and you've got until the end of the following month to get those IFTA reports together and filed. And in addition to that, your IFTA renewal must be done by the end of the year.
If you're currently thinking to yourself, "I really wish I didn't have to deal with anything IFTA related," then you my friend are our type of person. Yes, we do IFTA too, so if you're in need of a hand just give us a call and we'll get you taken care of.
So while it may not be something that can be wrapped, bagged, or even placed under the tree, give yourself the gift of TSNAmerica this holiday season. With all the bustle going on around this time of year, who has time to deal with registrations and renewals? Only us—that's who. So give us a call at 803.386.0320 and let us make your holiday season by taking the paperwork out of your way!
Please note that we will be out of the office on Christmas eve, Christmas day, New Year's eve, and New Year's day, so if you need anything during that time, we'll be offering emergency email support during those times at support@tsnamerica.com.


Lao and The Death of Asian America?
Over at the Hyphen blog, Chris Fan is taking Jean Quan to task for her handling of Occupy Oakland, but also taking it an extra step further and suggesting that the concept of Asian America itself may be dying.
Quan was once a part of a body of progressive thinkers who really pushed to create ethnic studies programs. Programs many readers of Little Laos on the Prairie have seen direct benefits from over the years.
There are many opportunities and policies that exist today because some brave people felt that honest discussions of the history and journeys of Asian Americans seriously had a place in American arts and letters, and also community-building policies and programs.
That being said, there are also many who don't recognize the short time such programs have really been possible, or the tremendous challenges the programs faced as we examined what could be as 'Asian Americans'. In and out of the classrooms, we see the concept of Asian America taken for granted by some, while others enjoy the benefits but have no respect for the journey, even to the extreme response of trying to roll back the progress that has been made.
There are a great many people who don't appreciate that the very notion of 'Asian America' as a coherent body has often threatened to implode.
It was never an inevitable given.
When you have over 60 different communities in the US, some with long-standing historical enmities overseas and even domestically, being told they ought to organize under a pan-Asian banner, we forget how fragile that alliance, that notion of organizing as 'Asian Americans' really is.
Afghanistan, Australia, Bangladesh, Bhutan, Brunei, Burma/Myanmar (the Shan and the Karen, among others), Cambodia, China, Cook Islands, Federated States of Micronesia, Federated States of Midway Islands, Fiji, French Polynesia, Guam, Hawaii's, Hong Kong, India, Indonesia, Iran, Japan, Kazakhstan, Kiribati, Kyrgyzstan, Laos (Hmong, Lao, Tai Dam, Khmu, Iu Mien and over 82 different ethnicities who live there), Macau, Malaysia, Maldives, Marshall Islands, Mongolia, Nauru, Nepal, New Caledonia, New Zealand, North Korea, Northern Mariana Islands, Pakistan, Palau, Papua New Guinea, Philippines, Pitcairn Islands, Samoa, Singapore, Solomon Islands, South Korea, Sri Lanka, Tahiti, Taiwan, Tajikistan, Thailand, Tibet, Tonga, Turkmenistan, Tuvalu, Uzbekistan, Vanuatu, and Vietnam (including the recently arrived Montagnards (Rhade,Bahnar, Jarai, Koho and Mnong).
And just like that, we're supposed to aggregate together, certain that once we speak as one voice, no one will be under-represented, and we will somehow be a fully functioning federation that consistently comes to the support of the other in times of distress, and in times of opportunity?
Whether it's immigration reform, health care reform, workers rights, or subjects such as unexploded ordnance, Agent Orange, or human trafficking, etc. how does Asian America ensure we all find a way to come to a constructive consensus and support one another to the fullest potential our collective voice is supposed to have?
I'm not saying it's impossible, but I am saying it's something that needs a lot more work over a lifetime than a catchy chant and a slogan.
For Lao, as a community, we're consistently excluded from serious discussions on issues facing our community both among policy makers and in academia. It does weigh on our minds, and we're seeing an increasing number of panels and community discussions debating our future directions in light of this.Will we start bypassing systems that will continually exclude us, even those that are ostensibly there to help us effectively speak with a greater voice?
If a system becomes irrelevant to our community, it won't necessarily be the death of that system, but neither would it be one I'd be in any hurry to engage my friends and families in.
For those of us who've worked on these issues over the decades, that's a bold claim, perhaps even hyperbolic when we consider other movements taking place around us, such as the work of Asian Pacific Islanders in Philanthropy. I wouldn't say we're really even close to putting nails in any coffins, but I would always encourage Asian American activists to keep pushing more for genuine systems change, and ways to engage others in that vision constructively.
There's a big difference between being an Asian in America and being Asian American, and being a part of Asian America.
As a community, Lao have to examine honestly the importance of engagement with these concepts. With a community of 200,000+ to 400,000+, depending on how you're doing the counting, we have people counting on us that means we cannot afford to be aligned with movements who throw us under the bus and take us for granted.
Next PostLao Minnesotans: Land of 10,000 Thanks?


text:
Q: how to use keyboard to navigate through li list? I have collapsible drop down ul. I need to navigate through it using up arrow key and down arrow key !!
This following example is demonstrating collabsible ul li list with input above.
and I have the complete example on CodePen

$(document).ready(function(){
// how to navigate to li using up and down arrows in keyboard

  $('#DdlInput').focus(function(){
    $('#mylist').slideDown(200);
  });
  $('#DdlInput').focusout(function(){
    $('#mylist').slideUp(200);
  });

$('#DdlInput').on("keyup", function() {
    var value = $(this).val().toLowerCase();
    $("#mylist li").filter(function() {     $(this).toggle($(this).text().toLowerCase().indexOf(value) > -1);
    });
  });
});
#mylist {
  list-style: none;
  width: 200px;
  border: 1px dashed gray;
  border-radius: .3em;
  padding: 0;
  display: none;
}
#mylist li{
  padding: 5px;
  padding-top:7px;
  border-bottom: 1px dashed gray;
}

<input id="DdlInput" type="text"/>

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Base

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A: I think this is the solution to your problem:

$('#DdlInput').focus(function () {
    $('#mylist').slideDown(200);
});
$('#DdlInput').focusout(function () {
    $('#mylist').slideUp(200);
});

var li = $('li');
var liSelected;

$("#DdlInput").keydown(function (e) {
    if (e.keyCode === 40) {
        if (liSelected) {
            liSelected.removeClass('selected');
            next = liSelected.next();
            if (next.length > 0) {
                liSelected = next.addClass('selected');
            } else {
                liSelected = li.eq(0).addClass('selected');
            }
        } else {
            liSelected = li.eq(0).addClass('selected');
        }

        console.log(liSelected[0].innerText);
        $("#DdlInput").val(liSelected[0].innerText);

    } else if (e.keyCode === 38) {
        if (liSelected) {
            liSelected.removeClass('selected');
            next = liSelected.prev();
            if (next.length > 0) {
                liSelected = next.addClass('selected');
            } else {
                liSelected = li.last().addClass('selected');
            }
        } else {
            liSelected = li.last().addClass('selected');
        }

        console.log(liSelected[0].innerText);

        $("#DdlInput").val(liSelected[0].innerText);
    }
});
#mylist {
    display: none;
}

li.selected {
    background: grey;
}

<input id="DdlInput" type="text" />

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redpajama_set_name: RedPajamaStackExchange


text:
Q: Next.js Hot Reload Mac OS Intel/M1 I'm fighting since couple of days, that with next.js the app with the build-in feature fast refresh is not working on Mac OS with M1 processor with intel processor everything works fine.
Using next.js latest version.
npx create-next-app@latest --typescript
Install simple example next.js + typescript.
Node Version 16.3.2 - npm version 8.1.2
I tried with different node versions via nvm.
Is there anyway to see some logs? I don't get any errors with npm run dev

A: After the posting of my issue. I found the solution.
I updated to the latest yarn version.
npm install --global yarn
Didn't know that this is connected.


text:
A report on Tone (linguistics)
Use of pitch in language to distinguish lexical or grammatical meaning – that is, to distinguish or to inflect words.
- Tone (linguistics)
Group of Sinitic languages and dialects that are natively spoken across most of northern and southwestern China.
Most Mandarin varieties have four tones.
Varieties of Chinese
Branch of the Sino-Tibetan language family consisting of hundreds of local varieties, many of which are not mutually intelligible.
All have phonemic tones, with northern varieties tending to have fewer distinctions than southern ones.
Sino-Tibetan languages
Family of more than 400 languages, second only to Indo-European in number of native speakers.
Tai and Miao–Yao were included because they shared isolating typology, tone systems and some vocabulary with Chinese.
Group of languages that form the Sinitic branch of the Sino-Tibetan languages family, spoken by the ethnic Han Chinese majority and many minority ethnic groups in Greater China.
All varieties of Chinese are tonal to at least some degree, and are largely analytic.
Phoneme
Unit of sound that can distinguish one word from another in a particular language.
Besides segmental phonemes such as vowels and consonants, there are also suprasegmental features of pronunciation (such as tone and stress, syllable boundaries and other forms of juncture, nasalization and vowel harmony), which, in many languages, change the meaning of words and so are phonemic.
Vietnamese language
Austroasiatic language originating from Vietnam where it is the national and official language.
Like many other languages in Southeast Asia and East Asia, Vietnamese is an analytic language with phonemic tone.
Official romanization system for Standard Mandarin Chinese in Mainland China, and to some extent, in Taiwan and Singapore.
The system includes four diacritics denoting tones, but pinyin without tone marks is used to spell Chinese names and words in languages written in the Latin script, and is also used in certain computer input methods to enter Chinese characters.
Tai language of the Kra–Dai language family spoken by the Central Thai people and a vast majority of Thai Chinese.
It is a tonal and analytic language, similar to Chinese and Vietnamese.
Tone sandhi
Tone sandhi is a phonological change occurring in tonal languages, in which the tones assigned to individual words or morphemes change based on the pronunciation of adjacent words or morphemes.
Unit of organization for a sequence of speech sounds typically made up of a syllable nucleus with optional initial and final margins (typically, consonants).
Although every syllable has supra-segmental features, these are usually ignored if not semantically relevant, e.g. in tonal languages.

redpajama_set_name: RedPajamaCommonCrawl


Many toddlers, schoolchildren and adults can not and will not do without a Trolley Backpack. The backpack trolleys are no longer a sole domain for seniors, but are favored by more and more young people. The reason for this is certainly the special transformation possibility, which has a trolley backpack.
Depending on what the trolley backpack is needed for, thanks to the sophisticated mechanical components, it can easily be converted into a backpack. The specially designed carrying system is hidden behind a cover and can easily be unfolded again if necessary. This results in optimal mobility, consisting of alternating driving on wheels and carrying on the shoulders.
The trolley backpacks, which are made by renowned brand manufacturers, are also characterized by excellent wearing comfort and are extremely durable. This is ensured, among other things, by the professionally selected materials, which are processed using complex technologies. These are joined together in a carefully thought-out design, creating a modern, customizable trolley.
The rucksacks produced by very different product developers and manufacturers, which are very similar in shape to the classic trolley, make it much easier to carry more or less heavy objects. Also, depending on its volume, much more utensils fit into a trolley than could be carried by hand.
The trolley rucksacks are a special variant of the usual trolleys and offer a wealth of great conditions. These concern both the material-technical aspects as well as the design and above all the ergonomics.
The various functional details such as wheels on the underside and a pull-to-hang bar make the trolley backpacks the ideal travel and school equipment. Especially with the backpack trolleys, the combination of trolley and conventional backpack is clearly visible. With these products, a significant better mobility is given and the physical burden of heavy wear is eliminated.
The successful combination of many innovations means that the trolley backpack has well-padded carrying straps that have been fixed to the most favorable parts of the body. The wheels have a high-quality ball bearing that can handle even extreme loads. The rollers are additionally protected by so-called hip fins. Excellent portability is ensured by the different positions of non-slip handles. The foldable carrying handles are located on the sides and at the top and bottom of the trolley backpack. The compact transient aid can thus be transported vertically or horizontally.
The storage space in the trolley is very generous and also includes a sensible subdivision through various inner compartments made of nylon and a front patch pocket.


text:
We're hiring Opinion columnists!
Interested in advocating for change at UT? Apply to be a columnist at The Daily Texan here.
Opinion ›
Section Pages
An oil-funded university is not sustainable
By Patrick Lee - Updated on June 26, 2019 at 6:06 pm
Columnist Patrick Lee argues that in order for UT to be a first-class institution, it must divest from fossil fuels.
Expanding sunscreen dispenser program would protect students
By Abby Springs - Updated on June 25, 2019 at 7:09 pm
Associate editor Abby Springs advocates for adding sunscreen dispensers to residence halls and high-traffic areas.
A future without Roe v. Wade jeopardizes female students
By Kaitlin Burns Passafiume - Updated on June 25, 2019 at 3:21 pm
Columnist Kaitlin Burns Passafiume argues that early-term abortion bans would have a negative impact on the UT student body and on female scholars everywhere.
School of Architecture must alleviate material costs
By Sanika Nayak - Updated on June 24, 2019 at 7:28 pm
Associate editor Sanika Nayak argues that the School of Architecture must help fund the cost of required materials for its students.
Requiring measles vaccine can protect students from outbreak
Associate editor Abby Springs advocates for requiring the measles vaccine for incoming students.
UT course schedules need to be released during spring break
By David West Jr. - Updated on June 11, 2019 at 2:10 pm
Columnist David West Jr. advocates for UT to release course schedules over spring break in order for students to dedicate the necessary preparation to their future courses.
You have a place on The Daily Texan's staff
By Spencer Buckner - Updated on June 10, 2019 at 9:34 pm
Editor-in-chief Spencer Buckner invites students to apply to the Texan's summer staff.
Editor-in-chief self-indulges one last time
By Liza Anderson - Updated on May 10, 2019 at 12:19 am
Editor-in-chief Liza Anderson says goodbye to The Daily Texan.
UT should learn from its mistakes and focus on transparency
By The Daily Texan Editorial Board - Updated on May 10, 2019 at 12:02 am
Reflecting on the year, the editorial board urges UT to focus on being more open with students going forward.
Out-of-state students want more resources at orientation
By Abhirupa Dasgupta - Updated on May 9, 2019 at 11:51 pm
Columnist Abhirupa Dasgupta finds that freshman orientation doesn't always address the specific concerns of out-of-state students.


If you or a family member have been hit by a car on a San Diego street or Los Angeles roadway and the driver fled the scene, you are not alone. You need an aggressive attorney who will be a tireless advocate for these accidents which occur with disturbing frequency in Southern California. The combination of uninsured drivers, the amount of people on the road, and a mix of motorcyclists and bicyclists create extremely dangerous conditions. Even if a driver who struck you does stop but they have no insurance, the compensation you need for medical bills may be extremely difficult to obtain. If the driver fled the scene, compensation may be even more difficult to get if they are never found.
If you are the victim or a hit-and-run accident or the driver who hit you was uninsured or underinsured, call The Law Office of Patrick G. Shea, APC for a free consultation: 619-528-4550.
Uninsured motorist coverage in California should cover your costs, but your insurance company may become combative and not offer a fair settlement of your claim if the other driver was uninsured or left the scene of the accident. Whether you are driving, walking, riding a bike or on a motorcycle, your own insurance should provide the financial support you need because, likely, you carry uninsured motorist coverage. But your insurance company may become an opponent rather than an advocate in such cases.
We will seek maximum compensation for you in any case you may have. Hit-and-run cases can become legally complex and medically expensive. Trust us to help you get the support you need, guide you through the process and aggressively protect your best interests. Our personal injury department is available for free consultations and free case evaluations. If we take your case, we only collect attorneys' fees if we win. So if we take your case, you can feel confident knowing we expect to win the settlement or judgment that you deserve.


text:
Q: Javascript launching with (or without) document.writeln? I have been looking at some tracking issues and have a question pertaining to the launching of scripts. Can someone tell me if there is a difference between:
<script type="text/javascript" src="http://www.example.com/universalPixel.html"></script>

and
<script language="JavaScript"> document.writeln('<scri' + 'pt type="text/javascript" src="http://www.example.com/universalPixel.html"></scri' + 'pt>');</script>

I have seen these two variations and unfortunately have not been able to discern if there is a significant difference dependent on the inclusion of the document.writeln method. Or perhaps another distinction that I am unaware of.
Thank you for your help.
Alex

A: document.writeln is probably used to dynamically include a script, using that strange string concatenation method because the browser processes </script> appearing anywhere as the end of the script tag, even inside of a JavaScript string.  So the following would not work correctly for that reason:
<script type="text/javascript">
    // code

    document.writeln('<script type="text/javascript" src="..."></script>");
    // ^^ the </script> above ends the previous <script> tag prematurely.

    // more code
</script>

But there are better methods:

*

*Just include them normally, using <script src="..">

*Dynamically generate includes using server-side code (i.e., PHP) instead of JavaScript

*Use a JS library that provides dynamic library loading.

A: Since document.writeLn is discouraged in XHTML, you should attempt to use option 1. Many strict browsers will even ignore the second item if the appropriate doctype is used.


text:
Jonathan Gabay
Branding expert and founder of Brand Forensics
Jonathan Gabay is a creative branding expert, founder of Brand Forensics and on the central Faculty of the world's biggest marketing institute.
As a journalist, Jonathan regularly delivers incisive comment and analysis in the national and trade press, including the Independent, Guardian Unlimited, Scotsman, mad.co.uk, Creative Match, What's New in Marketing, as well as on CNN, SKY, BBC, Channel 4, Five and ITN.
He has addressed business gatherings all over the world and graduates at various academic institutions including, the London School of Economics, Management Centre Europe and Newport University. Jonathan is rated as one of the most popular lecturers at the Chartered Institute of Marketing, delivering lectures to senior managers around the world. He recently contributed to the Institute's White Paper document on a new global definition of marketing and in early 2008 he represented the CIM at a major business debate at the House of Commons concerning global warming and marketing. He Won!... Emphatically!
Leading business organisations as well as UK FTSE companies in sectors ranging from finance and technology to FMCG and travel, feature Jonathan's award winning copywriting and marketing strategies.
His experience of working for some of the best known creative agencies and brands in the industry – including heading up departments at some of the UK's top agencies - has shaped his work as an author and Jonathan has several best selling business books, many of which are now used as standard texts for marketing study and been translated throughout the world.
Jonathan Gabay's rare fusion of corporate experience, strong audience rapport and academic understanding gives him significant status on the speaking and conference circuit.
By cutting out unnecessary jargon 'the camouflage of the incompetent' and dry analytical prose, Jonathan's approach provides insight and entertainment in equal measure and his incisive comment on brand-related issues will get to the heart of any event.
Clients often ask about purchasing books for giveaways and delegate packs. Below you'll find a selection of products by Jonathan Gabay. Click the images to view on Amazon's website. For bulk orders, please speak with your Booking Agent.
To book Jonathan Gabay, please submit an online enquiry, send us an email or speak with one of our friendly booking agents on +44 (0)1372 361 004.
Robin Sieger
Hamish Taylor
Professor James Woudhuysen
Greg Nugent
I was very pleased with the service I received from NMP Live, the agent was very helpful and professional. I will definitely look to NMP Live in the future.
Nicole Hardaker, EAIE Conference Programme Coordinator


Wilson's additions are enclosed in square brackets [ ] and the original positions of space groups transferred by him by round brackets ( ). Space groups not listed belong to the `impossible' category.
†Kitajgorodskij (1961 ) includes Pnnm at this position, but this is inconsistent with the text of either the Russian or the English version.
‡Kitajgorodskij (1961 ) correctly includes Pbcm at this position.