title: James A. Lindsay

text: Lindsay is a critic of "woke culture", which he analogizes to religious belief. He describes "the Social Justice Movement" as his "ideological enemy". Though he opposed Donald Trump in the 2016 United States presidential election, Lindsay announced his intention to vote for Trump in the 2020 election, arguing that the danger of "wokeness" is much greater than that of a Trump presidency.


title: James A. Lindsay

text: Lindsay is credited as one of the leading voices popularizing the term "groomer" as a pejorative directed at LGBTQ educators and activists by members of the political right, and has referred to the Pride flag as "the flag of a hostile enemy."


title: James A. Lindsay

text: In 2021, Lindsay wrote on Twitter that "there will be" a genocide of whites if critical race theory "isn't stopped." His statement was met with widespread criticism, including from "Quillette" founder Claire Lehmann who wrote, "James Lindsay is now peddling White Genocide Theory. Implying that a genocide against whites in the U.S. is imminent has the potential to inspire racist violence. Such comments are extreme, reckless, and irresponsible. They should be denounced.”


title: Leeward Islands

text: The Leeward Islands () are a group of islands situated where the northeastern Caribbean Sea meets the western Atlantic Ocean. Starting with the Virgin Islands east of Puerto Rico, they extend southeast to Guadeloupe and its dependencies. In English, the term "Leeward Islands" refers to the northern islands of the Lesser Antilles chain. The more southerly part of this chain, starting with Dominica, is called the Windward Islands. Dominica was originally considered a part of the Leeward Islands, but was transferred from the British Leeward Islands to the British Windward Islands in 1940.


title: Leeward Islands

text: The name of this island group, "Leeward Islands", dates from previous centuries, when sailing ships were the sole form of transportation across the Atlantic Ocean. In sailing terminology, 'windward' means towards the source of the wind (upwind), while 'leeward' is the opposite direction (downwind). In the West Indies, the prevailing winds, known as the trade winds, blow predominantly out of the northeast. Therefore, a sailing vessel departing from the British Gold Coast and the Gulf of Guinea, driven by the trade winds, would normally first encounter Dominica and Martinique, islands most to windward, in their west-northwesterly heading to the final destinations in the Caribbean, Central America, and Northern America. This location, Dominica and Martinique, becomes the rough dividing line between the Windward Islands and the Leeward Islands.


title: Leeward Islands

text: The early Spanish colonizers called Puerto Rico and the islands to the west "Sotavento", meaning 'leeward'. The islands to the south and east of Puerto Rico were then called "Islas de Barlovento", meaning 'windward islands'. When the British gained control of many of the Lesser Antilles, they designated Antigua, Montserrat and the islands to the north as the 'Leeward Islands'. Guadeloupe and the islands to the south were designated as the 'Windward Islands'. Later on, all islands north of Martinique became known as the Leeward Islands. Dominica was transferred to the British Windward Islands in 1940, and is now considered to be part of the Windward Islands.


title: Leeward Islands

text: However, even in modern usage in languages other than English, notably, Dutch, French, and Spanish, all of the Lesser Antilles from the Virgin Islands to Trinidad and Tobago are known as 'the Windward Islands' ("Bovenwindse Eilanden" in Dutch, "Îles du Vent" in French, and "Islas de Barlovento" in Spanish). The ABC islands and the other islands along the Venezuelan coast, known in English as the Leeward Antilles, are known in languages other than English as 'the Leeward Islands'.


title: Leeward Islands

text: According to the Fijian language dictionary, published in 1872, it is stated that the Leeward Islands were called "Ra" during that time.


title: Leeward Islands

text: The islands are affected by active volcanism, and notable eruptions have occurred in Montserrat in the 1990s and in 2009 to 2010. At , the highest point is La Grande Soufrière in Guadeloupe.


title: Leeward Islands

text: The Caribs, after whom the Caribbean is named, are believed to have migrated from the Orinoco River area in Venezuela in South America to settle in the Caribbean islands about 1200 AD, according to carbon dating. Over the century leading up to Columbus' arrival in the Caribbean archipelago in 1492, the Caribs mostly displaced the Maipurean-speaking Taínos, who settled the island chains earlier in history, by warfare, extermination and assimilation.


title: Leeward Islands

text: The islands were among the first parts of the Americas to fall under the control of the Spanish Empire. European contact commenced with Christopher Columbus's second voyage; many of the islands' names originate from this period: Montserrat was named in honour of Santa Maria de Montserrat (Our Lady of Montserrat), after the Blessed Virgin of the Monastery of Montserrat, which is located on the Mountain of Montserrat, the national shrine of Catalonia. 'Mont serrat' in Catalan means 'saw mountain', referring to the serrated appearance of the mountain range.


title: Leeward Islands

text: Although comparatively much smaller than the surrounding islands in the Caribbean, the Leeward Islands posed the most significant rebellion to the British Stamp Act, though it was decidedly less severe in comparison to that of the mainland North American colonies.


title: Leeward Islands

text: In 1660, there were about 8,000 white settlers and approximately 2,000 African slaves in the Leeward Islands. However, that ratio narrowed over succeeding years. In 1678, there were 10,408 white settlers and 8,449 black slaves. By 1708, there was a huge disparity between the number of white settlers, which had declined to 7,311, while the number of black slaves was estimated at 23,500.


title: Leeward Islands

text: In 1816, the colony as a federation of islands was dissolved, and the individual islands were ruled individually. However, the colony of the Leeward Islands was re-established in 1833.


title: Leeward Islands

text: There are two countries and eleven territories in the Leeward Islands. From the northwest to the southeast, the main islands are:


title: Doxepin

text: Doxepin is a medication falling in the tricyclic antidepressant (TCA) class used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.


title: Doxepin

text: Common side effects include sleepiness, dry mouth, constipation, nausea, and blurry vision. Serious side effects may include increased risk of suicide in those under the age of 25, mania, and urinary retention. A withdrawal syndrome may occur if the dose is rapidly decreased. Use during pregnancy and breastfeeding is not generally recommended. Doxepin is a tricyclic antidepressant (TCA). Although how it works for treating depression remains an area of active inquiry, it may involve increasing the levels of norepinephrine, along with blocking histamine, acetylcholine, and serotonin.


title: Doxepin

text: Doxepin was approved for medical use in the United States in 1969. It is available as a generic medication. In 2020, it was the 252nd most commonly prescribed medication in the United States, with more than 1million prescriptions.


title: Doxepin

text: Doxepin is used as a pill to treat major depressive disorder, anxiety disorders, and chronic hives, and for short-term help with trouble remaining asleep after going to bed (a form of insomnia). As a cream it is used for short-term treatment of itchiness caused by atopic dermatitis or lichen simplex chronicus.


title: Doxepin

text: Doxepin is used in the treatment of insomnia. In 2016, the American College of Physicians advised that insomnia be treated first by treating comorbid conditions, then with cognitive behavioral therapy and behavioral changes, and then with drugs; doxepin was among those recommended for short-term help maintaining sleep, on the basis of weak evidence. The 2017 American Academy of Sleep Medicine recommendations focused on treatment with drugs were similar. A 2015 Agency for Healthcare Research and Quality review of treatments for insomnia had similar findings.


title: Doxepin

text: A major systematic review and network meta-analysis of medications for the treatment of insomnia published in 2022 found that doxepin had an effect size (standardized mean difference (SMD)) against placebo for treatment of insomnia at 4weeks of 0.30 (95% –0.05 to 0.64). The certainty of evidence was rated as very low, and no data were available for longer-term treatment (3months). For comparison, the other sedating antihistamines assessed, trimipramine and doxylamine, had effect sizes (SMD) at 4weeks of 0.55 (95% CI –0.11 to 1.21) (very low certainty evidence) and 0.47 (95% CI 0.06 to 0.89) (moderate certainty evidence), respectively. Benzodiazepines and Z-drugs generally showed larger effect sizes (e.g., SMDs of 0.45 to 0.83) than doxepin, whereas the effect sizes of orexin receptor antagonists, such as suvorexant, were more similar (SMDs of 0.23 to 0.44).


title: Doxepin

text: Doses of doxepin used for sleep normally range from 3 to 6mg, but high doses of up to 25 to 50mg may be used as well.


title: Doxepin

text: A 2010 review of treatments for chronic hives found that doxepin had been superseded by better drugs but was still sometimes useful as a second-line treatment.


title: Doxepin

text: Its use in pregnant and lactating women is advised against, although the available evidence suggests it is unlikely to cause negative effects on fetal development. The lack of evidence from human studies, however, means it is currently impossible to rule out any risk to the fetus and it is known to cross the placenta. Doxepin is secreted in breast milk and neonatal cases of respiratory depression in association with maternal doxepin use have been reported.


title: Doxepin

text: Doxepin's side effects profile may differ from the list below in some countries where it is licensed to be used in much smaller doses (viz., 3 mg and 6 mg).


title: Doxepin

text: The side effects of low-dose doxepin for insomnia in long-term clinical trials (28 to 85days) in adults and elderly people were as follows:


title: Doxepin

text: Like other TCAs, doxepin is highly toxic in cases of overdose. Mild symptoms include drowsiness, stupor, blurred vision, and excessive dryness of mouth. More serious adverse effects include respiratory depression, hypotension, coma, convulsions, cardiac arrhythmia, and tachycardia. Urinary retention, decreased gastrointestinal motility (paralytic ileus), hyperthermia (or hypothermia), hypertension, dilated pupils, and hyperactive reflexes are other possible symptoms of doxepin overdose. Management of overdose is mostly supportive and symptomatic, and can include the administration of a gastric lavage so as to reduce absorption of the doxepin. Supportive measures to prevent respiratory aspiration is also advisable. Antiarrhythmic agents may be an appropriate measure to treat cardiac arrhythmias resulting from doxepin overdose. Slow intravenous administration of physostigmine may reverse some of the toxic effects of overdose such as anticholinergic effects. Haemodialysis is not recommended due to the high degree of protein binding with doxepin. ECG monitoring is recommended for several days after doxepin overdose due to the potential for cardiac conduction abnormalities.


title: Doxepin

text: Doxepin should not be used within 14 days of using a monoamine oxidase inhibitor (MAOI) such as phenelzine due to the potential for hypertensive crisis or serotonin syndrome to develop. Its use in those taking potent CYP2D6 inhibitors such as fluoxetine, paroxetine, sertraline, duloxetine, bupropion, and quinidine is recommended against owing to the potential for its accumulation in the absence of full CYP2D6 catalytic activity. Hepatic enzyme inducers such as carbamazepine, phenytoin, and barbiturates are advised against in patients receiving TCAs like doxepin owing to the potential for problematically rapid metabolism of doxepin to occur in these individuals. Sympathomimetic agents may have their effects potentiated by TCAs like doxepin. Doxepin also may potentiate the adverse effects of anticholinergic agents such as benztropine, atropine and hyoscine (scopolamine). Tolazamide, when used in conjunction with doxepin has been associated with a case of severe hypoglycaemia in a type II diabetic individual. Cimetidine may influence the absorption of doxepin. Alcohol may potentiate some of the CNS depressant effects of doxepin. Antihypertensive agents may have their effects mitigated by doxepin. Cotreatment with CNS depressants such as the benzodiazepines can cause additive CNS depression. Co-treatment with thyroid hormones may also increase the potential for adverse reactions.


title: Doxepin

text: Doxepin is a tricyclic antidepressant (TCA). It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) (a reuptake inhibitor of serotonin and norepinephrine), with additional antiadrenergic, antihistamine, antiserotonergic, and anticholinergic activities.


title: Doxepin

text: Doxepin is a reuptake inhibitor of serotonin and norepinephrine, or a serotonin–norepinephrine reuptake inhibitor (SNRI), and has additional antiadrenergic, antihistamine, antiserotonergic, and anticholinergic activities. It is specifically an antagonist of the histamine H and H receptors, the serotonin 5-HT and 5-HT receptors, the α-adrenergic receptor, and the muscarinic acetylcholine receptors (M–M). Similarly to other tricyclic antidepressants, doxepin is often prescribed as an effective alternative to SSRI medications. Doxepin is also a potent blocker of voltage-gated sodium channels, and this action is thought to be involved in both its lethality in overdose and its effectiveness as an analgesic (including in the treatment of neuropathic pain, and as a local anesthetic). The potencies of doxepin in terms of its receptor antagonism specifically are as follows:


title: Doxepin

text: Based on its values for monoamine reuptake inhibition, doxepin is relatively selective for the inhibition of norepinephrine reuptake, with a much weaker effect on the serotonin transporter. Although there is a significant effect that takes place at one of the specific serotonergic binding sites, the 5-HT serotonin receptor subtype. There is negligible influence on dopamine reuptake.


title: Doxepin

text: The major metabolite of doxepin, nordoxepin (desmethyldoxepin), is pharmacologically active similarly, but relative to doxepin, is much more selective as a norepinephrine reuptake inhibitor. In general, the demethylated variants of tertiary amine TCAs like nordoxepin are much more potent inhibitors of norepinephrine reuptake, less potent inhibitors of serotonin reuptake, and less potent in their antiadrenergic, antihistamine, and anticholinergic activities.


title: Doxepin

text: Antidepressant doses of doxepin are defined as 25 to 300 mg/day, although are typically above 75 mg/day. Antihistamine doses, including for dermatological uses and as a sedative/hypnotic for insomnia, are considered to be 3 to 25 mg, although higher doses between 25 and 50 mg and in some cases even up to 150 mg have been used to treat insomnia. At low doses, below 25 mg, doxepin is a pure antihistamine and has more of a sedative effect. At antidepressant doses of above 75 mg, doxepin is more stimulating with antiadrenergic, antiserotonergic, and anticholinergic effects, and these activities contribute to its side effects.


title: Doxepin

text: Doxepin is a mixture of ("E") and ("Z") stereoisomers with an approximate ratio of 85:15. When doxepin was developed, no effort was made to separate or balance the mixture following its synthesis, resulting in the asymmetric ratio. ("Z")-Doxepin is more active as an inhibitor of serotonin and norepinephrine reuptake than ("E")-doxepin. The selectivity of doxepin for inhibition of norepinephrine reuptake over that of serotonin is likely due to the 85% presence of ("E")-doxepin in the mixture. Most other tertiary amine TCAs like amitriptyline and imipramine do not exhibit "E"-"Z" isomerism or such mixture asymmetry and are comparatively more balanced inhibitors of serotonin and norepinephrine reuptake.


title: Doxepin

text: Doxepin is a highly potent antihistamine, with this being its strongest activity. In fact, doxepin has been said to be the most or one of the most potent H receptor antagonists available, with one study finding an "in vitro" K of 0.17 nM. It is the most potent and selective H receptor antagonist of the TCAs (although the "tetracyclic" antidepressant (TeCA) mirtazapine is slightly more potent), and other sedating antihistamines, for instance the over-the-counter diphenhydramine (K = 16 nM) and doxylamine (K = 42 nM), show far lower affinities for this receptor in comparison. The affinity of doxepin for the H receptor is far greater than its affinity for other sites, and 10- to 100-fold higher doses are needed for antidepressant effects. In accordance, although it is often described as a "dirty drug" due to its highly promiscuous binding profile, doxepin acts as a highly selective antagonist of the H receptor at very low doses (less than 10 mg; typically 3 to 6 mg). At these doses, it notably has no clinically relevant anticholinergic effects such as dry mouth or cognitive/memory impairment, unlike most other sedating antihistamines, and similarly has no effect on other receptors such as adrenergic and serotonin receptors.


title: Doxepin

text: The H receptor antagonism of doxepin is responsible for its hypnotic effects and its effectiveness in the treatment of insomnia at low doses. The incidence of side effects with doxepin and its safety at these doses was similar to that of placebo in clinical trials; the most frequent side effects were headache and somnolence/sedation, both with an incidence of less than 5%. Other side effects sometimes associated with antihistamines, including daytime sedation, increased appetite, and weight gain, all were not observed. Clinical evidence of H receptor antagonists and TCAs for the treatment insomnia shows mixed effectiveness and is limited in its quality due to weaknesses like small sample sizes and poor generalizability. However, doxepin is a unique and notable exception; it has been well-studied in the treatment of insomnia and shows consistent benefits with excellent tolerability and safety. Aside from diphenhydramine and doxylamine, which have historical approval as hypnotics, doxepin is the only H receptor antagonist that is specifically approved for the treatment of insomnia in the United States.


title: Doxepin

text: The effect sizes of very low-dose doxepin in the treatment of insomnia range from small to medium. These include subjective and objective measures of sleep maintenance, sleep duration, and sleep efficiency. Conversely, very low-dose doxepin shows relatively weak effects on sleep initiation and does not significantly separate from placebo on this measure. This is in contrast to benzodiazepines and nonbenzodiazepine (Z-drug) hypnotics, which are additionally effective in improving sleep onset latency. However, it is also in contrast to higher doses of doxepin (50 to 300 mg/day), which "have" been found to significantly reduce latency to sleep onset. A positive dose–response relationship on sleep measures was observed for doses of doxepin between 1 and 6 mg in clinical studies, whereas the incidence of adverse effects remained constant across this dose range in both young and older adults. However, the incidence of adverse effects appeared to increase with longer treatment duration. A dose of doxepin as low as 1 mg/day was found to significantly improve most of the assessed sleep measures, but unlike the 3 and 6 mg/day doses, was not able to improve wake time during sleep. This, along with greater effect sizes with the higher doses, was likely the basis for the approval of the 3 and 6 mg doses of doxepin for insomnia and not the 1 mg dose.


title: Doxepin

text: At very low doses, doxepin has not shown discontinuation or withdrawal effects nor rebound insomnia. Sustained effectiveness without apparent tolerance was demonstrated in clinical studies of up to 12 weeks duration. This appears to be in contrast to over-the-counter antihistamines like diphenhydramine and doxylamine and all other first-generation antihistamines, which are associated with rapid development of tolerance and dependence (by day 3 or 4 of continuous dosing) and loss of hypnotic effectiveness. It is for this reason that, unlike doxepin, they are not recommended for the chronic management of insomnia and are advised for only short-term treatment (i.e., 1 week). It is not entirely clear why doxepin and first-generation antihistamines are different in this regard, but it has been suggested that it may have to do with the lack of selectivity for the H receptor of the latter or may have to do with the use of optimal doses. Unlike very-low-dose doxepin, most first-generation antihistamines also have marked anticholinergic activity as well as associated side effects such as dry mouth, constipation, urinary retention, and confusion. This is particularly true in older people, and antihistamines with concomitant anticholinergic effects are not recommended in adults over the age of 65. Anticholinergic activity notably may interfere with the sleep-promoting effects of H receptor blockade.


title: Doxepin

text: Antagonism of the H, 5-HT, 5-HT, and α-adrenergic receptors is thought to have sleep-promoting effects and to be responsible for the sedative effects of TCAs including those of doxepin. Although doxepin is selective for the H receptor at doses lower than 25 mg, blockade of serotonin and adrenergic receptors may also be involved in the hypnotic effects of doxepin at higher doses. However, in contrast to very low doses of doxepin, rebound insomnia and daytime sedation are significantly more frequent than placebo with moderate doses (25 to 50 mg/day) of the drug. In addition, one study found that although such doses of doxepin improved sleep measures initially, most of the benefits were lost with chronic treatment (by 4 weeks). Due to limited data however, more research on potential tolerance and withdrawal effects of moderate doses of doxepin is needed. At these doses of doxepin, dry mouth, an anticholinergic effect, was common (71%), and other side effects such as headache (25%), increased appetite (21%), and dizziness (21%) were also frequently observed, although these adverse effects were notably not significantly more frequent than with placebo in the study in question. In any case, taken together, higher doses of doxepin than very low doses are associated with an increased rate of side effects as well as apparent loss of hypnotic effectiveness with chronic treatment.


title: Doxepin

text: Doxepin at a dose of 25 mg/day for 3 weeks has been found to decrease cortisol levels by 16% in adults with chronic insomnia and to increase melatonin production by 26% in healthy volunteers. In individuals with neuroendocrine dysregulation in the form of nocturnal melatonin deficiency presumably due to chronic insomnia, very-low-dose doxepin was found to restore melatonin levels to near-normal values after 3 weeks of treatment. These findings suggest that normalization of the hypothalamic–pituitary–adrenal axis and the circadian sleep–wake cycle may be involved in the beneficial effects of doxepin on sleep and insomnia.


title: Doxepin

text: Doxepin has been identified as an inhibitor of CYP2D6 "in vivo" in a study of human patients being treated with 75 to 250 mg/day for depression. While it significantly altered metabolic ratios for sparteine and its metabolites, doxepin did not convert any of the patients to a different metabolizer phenotype (e.g., extensive to intermediate or poor). Nonetheless, inhibition of CYP2D6 by doxepin could be of clinical importance.


title: Doxepin

text: Doxepin is well-absorbed from the gastrointestinal tract but between 55 and 87% undergoes first-pass metabolism in the liver, resulting in a mean oral bioavailability of approximately 29%. Following a single very low dose of 6 mg, peak plasma levels of doxepin are 0.854 ng/mL (3.06 nmol/L) at 3 hours without food and 0.951 ng/mL (3.40 nmol/L) at 6 hours with food. Plasma concentrations of doxepin with antidepressant doses are far greater, ranging between 50 and 250 ng/mL (180 to 900 nmol/L). Area-under-curve levels of the drug are increased significantly when it is taken with food.


title: Doxepin

text: Doxepin is widely distributed throughout the body and is approximately 80% plasma protein-bound, specifically to albumin and α-acid glycoprotein.


title: Doxepin

text: Doxepin is extensively metabolized by the liver via oxidation and "N"-demethylation. Its metabolism is highly stereoselective. Based on "in vitro" research, the major enzymes involved in the metabolism of doxepin are the cytochrome P450 enzymes CYP2D6 and CYP2C19, with CYP1A2, CYP2C9, and CYP3A4 also involved to a lesser extent. The major active metabolite of doxepin, nordoxepin, is formed mainly by CYP2C19 (>50% contribution), while CYP1A2 and CYP2C9 are involved to a lesser extent, and CYP2D6 and CYP3A4 are not involved. Both doxepin and nordoxepin are hydroxylated mainly by CYP2D6, and both doxepin and nordoxepin are also transformed into glucuronide conjugates. The elimination half-life of doxepin is about 15–18 hours, whereas that of nordoxepin is around 28–31 hours. Up to 10% of Caucasian individuals show substantially reduced metabolism of doxepin that can result in up to 8-fold elevated plasma concentrations of the drug compared to normal.


title: Doxepin

text: Nordoxepin is a mixture of ("E") and ("Z") stereoisomers similarly to doxepin. Whereas pharmaceutical doxepin is supplied in an approximate 85:15 ratio mixture of ("E")- and ("Z")-stereoisomers and plasma concentrations of doxepin remain roughly the same as this ratio with treatment, plasma levels of the ("E")- and ("Z")-stereoisomers of nordoxepin, due to stereoselective metabolism of doxepin by cytochrome P450 enzymes, are approximately 1:1.


title: Doxepin

text: Doxepin is eliminated primarily in the urine and predominantly in the form of glucuronide conjugates, with less than 3% of a dose excreted unchanged as doxepin or nordoxepin.


title: Doxepin

text: Since doxepin is mainly metabolized by CYP2D6, CYP2C9, and CYP2C19, genetic variations within the genes coding for these enzymes can affect its metabolism, leading to changes in the concentrations of the drug in the body. Increased concentrations of doxepin may increase the risk for side effects, including anticholinergic and nervous system adverse effects, while decreased concentrations may reduce the drug's efficacy.


title: Doxepin

text: Individuals can be categorized into different types of cytochrome P450 metabolizers depending on which genetic variations they carry. These metabolizer types include poor, intermediate, extensive, and ultrarapid metabolizers. Most people are extensive metabolizers, and have "normal" metabolism of doxepin. Poor and intermediate metabolizers have reduced metabolism of the drug as compared to extensive metabolizers; patients with these metabolizer types may have an increased probability of experiencing side effects. Ultrarapid metabolizers break down doxepin much faster than extensive metabolizers; patients with this metabolizer type may have a greater chance of experiencing pharmacological failure.


title: Doxepin

text: A study assessed the metabolism of a single 75 mg oral dose of doxepin in healthy volunteers with genetic polymorphisms in CYP2D6, CYP2C9, and CYP2C19 enzymes. In CYP2D6 extensive, intermediate, and poor metabolizers, the mean clearance rates of ("E")-doxepin were 406, 247, and 127 L/hour, respectively (~3-fold difference between extensive and poor). In addition, the bioavailability of ("E")-doxepin was about 2-fold lower in extensive relative to poor CYP2D6 metabolizers, indicating a significant role of CYP2D6 in the first-pass metabolism of ("E")-doxepin. The clearance of ("E")-doxepin in CYP2C9 slow metabolizers was also significantly reduced at 238 L/hour. CYP2C19 was involved in the metabolism of ("Z")-doxepin, with clearance rates of 191 L/hour in CYP2C19 extensive metabolizers and 73 L/hour in poor metabolizers (~2.5-fold difference). Area-under-the-curve (0–48 hour) levels of nordoxepin were dependent on the genotype of CYP2D6 with median values of 1.28, 1.35, and 5.28 nM•L/hour in CYP2D6 extensive, intermediate, and poor metabolizers, respectively (~4-fold difference between extensive and poor). Taken together, doxepin metabolism appears to be highly stereoselective, and CYP2D6 genotype has a major influence on the pharmacokinetics of ("E")-doxepin. Moreover, CYP2D6 poor metabolizers, as well as patients taking potent CYP2D6 inhibitors (which can potentially convert a CYP2D6 extensive metabolizer into a poor metabolizer), may be at an increased risk for adverse effects of doxepin due to their slower clearance of the drug.


title: Doxepin

text: Another study assessed doxepin and nordoxepin metabolism in CYP2D6 ultra-rapid, extensive, and poor metabolizers following a single 75 mg oral dose. They found up to more than 10-fold variation in total exposure to doxepin and nordoxepin between the different groups. The researchers suggested that in order to achieve equivalent exposure, based on an average dose of 100%, the dosage of doxepin might be adjusted to 250% in ultra-rapid metabolizers, 150% in extensive metabolizers, 50% in intermediate metabolizers, and 30% in poor metabolizers.


title: Doxepin

text: Doxepin is a tricyclic compound, specifically a dibenzoxepin, and possesses three rings fused together with a side chain attached in its chemical structure. It is the only TCA with a dibenzoxepin ring system to have been marketed. Doxepin is a tertiary amine TCA, with its side chain-demethylated metabolite nordoxepin being a secondary amine. Other tertiary amine TCAs include amitriptyline, imipramine, clomipramine, dosulepin (dothiepin), and trimipramine. Doxepin is a mixture of ("E") and ("Z") stereoisomers (the latter being known as "cidoxepin" or "cis"-doxepin) and is used commercially in a ratio of approximately 85:15. The chemical name of doxepin is ("E"/"Z")-3-(dibenzo["b","e"]oxepin-11(6"H")-ylidene)-"N","N"-dimethylpropan-1-amine and its free base form has a chemical formula of CHNO with a molecular weight of 279.376 g/mol. The drug is used commercially almost exclusively as the hydrochloride salt; the free base has been used rarely. The CAS Registry Number of the free base is 1668-19-5 and of the hydrochloride is 1229-29-4.


title: Doxepin

text: Doxepin was discovered in Germany in 1963 and was introduced in the United States as an antidepressant in 1969. It was subsequently approved at very low doses in the United States for the treatment of insomnia in 2010.


title: Doxepin

text: "Doxepin" is the generic name of the drug in English and German and its and , while "doxepin hydrochloride" is its , , , and . Its generic name in Spanish and Italian and its are "doxepina", in French and its are "doxépine", and in Latin is "doxepinum".


title: Doxepin

text: The "cis" or ("Z") stereoisomer of doxepin is known as "cidoxepin", and this is its while "cidoxepin hydrochloride" is its .


title: Doxepin

text: Doxepin is marketed under many brand names worldwide, including: Adnor, Anten, Antidoxe, Colian, Deptran, Dofu, Doneurin, Dospin, Doxal, Doxepini, Doxesom, Doxiderm, Flake, Gilex, Ichderm, Li Ke Ning, Mareen, Noctaderm, Oxpin, Patoderm, Prudoxin, Qualiquan, Quitaxon, Sagalon, Silenor, Sinepin, Sinequan, Sinquan, and Zonalon. It is also marketed as a combination drug with levomenthol under the brand name Doxure.


title: Doxepin

text: The oral formulations of doxepin are -approved for the treatment of depression and sleep-maintenance insomnia, and its topical formulations are FDA-approved the short-term management for some itchy skin conditions. In Australia and the United Kingdom, the only licensed indications are in the treatment of major depression and pruritus in eczema.


title: Doxepin

text: Cidoxepin is under development by Elorac, Inc. for the treatment of chronic urticaria (hives). As of 2017, it is in phase II clinical trials for this indication. The drug was also under investigation for the treatment of allergic rhinitis, atopic dermatitis, and contact dermatitis, but development for these indications was discontinued.


title: Doxepin

text: Doxepin was under development by Winston Pharmaceuticals in an intranasal formulation for the treatment of headache. As of August 2015, it was in phase II clinical trials for this indication. Oxetorone is an antimigraine agent.


title: Doxepin

text: As of 2017, there was no good evidence that topical doxepin was useful to treat localized neuropathic pain.


title: Lemonade

text: There are varieties of lemonade found throughout the world. In North America and South Asia, cloudy still lemonade is the most common variety. There it is traditionally a homemade drink using lemon juice, water, and a sweetener such as cane sugar, simple syrup or honey. In the United Kingdom, Ireland, Central Europe, Australia, and New Zealand, a carbonated lemonade soft drink is more common. Despite the differences between the drinks, each is known simply as "lemonade" in countries where it is dominant.


title: Lemonade

text: The suffix "-ade" may also be applied to other similar drinks made with different fruits, such as limeade, orangeade, or cherryade.


title: Lemonade

text: A drink made with lemons, dates, and honey was consumed in 13th and 14th century Egypt, including a lemon juice drink with sugar, known as "qatarmizat". In 1676, a company known as "Compagnie de Limonadiers" sold lemonade in Paris. Vendors carried tanks of lemonade on their backs and dispensed cups of the soft drink to Parisians.


title: Lemonade

text: While carbonated water was invented by Joseph Priestley in 1767, the first reference found to carbonated lemonade was in 1833 when the drink was sold in British refreshment stalls. R. White's Lemonade has been sold in the UK since 1845.


title: Lemonade

text: The predominant form of lemonade found in the US, Canada, and India, cloudy lemonade, also known as traditional or old fashioned lemonade in the UK and Australia, is non-carbonated and made with fresh lemon juice; however, commercially produced varieties are also available. Generally served cold, cloudy lemonade may also be served hot as a remedy for congestion and sore throats, frozen, or used as a mixer.


title: Lemonade

text: Traditionally, children in US and Canadian neighborhoods start lemonade stands to make money during the summer months. The concept has become iconic of youthful summertime Americana to the degree that parodies and variations on the concept exist across media. References can be found in comics and cartoons such as "Peanuts", and the 1979 computer game "Lemonade Stand".


title: Lemonade

text: A popular variation of traditional lemonade, pink lemonade, is created by adding additional fruit juices, flavors, or food coloring to the recipe. Most store-bought pink lemonade is simply colored with concentrated grape juice or dyes.


title: Lemonade

text: A 1912 obituary credited the invention of pink lemonade to circus worker Henry E. "Sanchez" Allott, saying he had dropped in red cinnamon candies by mistake.


title: Lemonade

text: Another origin story credits another circus worker, Pete Conklin, in 1857. His brother George Conklin tells the story in his 1921 memoir. According to the story, Conklin's lemonade was a mixture of water, sugar and tartaric acid, with the tub garnished with a single lemon that he repeatedly used for the season. One day, he ran out of water. Searching desperately, he found a tub of water a bareback rider had recently used to rinse her pink tights. Adding in the sugar, acid and remaining bits of lemon, he offered the resulting mixture as "strawberry lemonade" and saw his sales double.


title: Lemonade

text: The predominant form of lemonade in the UK, Ireland, France, Germany, Switzerland, South Africa and Australia is a clear, lemon-flavoured carbonated beverage. Schweppes, R. White's Lemonade and C&C are common brands, and shops usually carry a store-branded lemonade as well. Schweppes uses a blend of lemon and lime oils. Other "fizzy drinks", "soft-drinks" (or pop) which are both lemon and lime flavoured may also sometimes be referred to as lemonade, such as Sprite and 7 Up. There are also speciality flavours, such as Fentimans Rose Lemonade, which is sold in the UK, the US, and Canada. Shandy, a mixture of beer and clear lemonade, is often sold pre-bottled, or ordered in pubs.


title: Lemonade

text: There are various drinks called brown lemonade. In Northern Ireland, brown lemonade is flavoured with brown sugar. A variant from Venezuela has cane sugar and lime.


title: Lemonade

text: In India and Pakistan, where it is commonly known as "nimbu paani", and in Bangladesh, lemonades may also contain salt and/or ginger juice. "Shikanjvi" is a traditional lemonade from this region, and can also be flavored with saffron, cumin and other spices.


title: Lemonade

text: Limonana, a type of lemonade made from freshly squeezed lemon juice and mint leaves, is a common summer drink in the Middle East. In Northern Africa, a drink called "cherbat" is made of lemon, mint, and rose water.


title: Lemonade

text: Switcha is a version of the drink made in the Bahamas and Turks & Caicos that can also be made with limes instead of lemons.


title: Lemonade

text: In France, it is common for bars or restaurants to offer citron pressé, also called citronnade, an unmixed version of lemonade in which the customer is given lemon juice, syrup and water separately to be mixed in their preferred proportions.


title: Lemonade

text: The high concentration of citric acid in lemon juice is the basis for popular culture recommendations of consumption of lemonade to prevent calcium-based kidney stones. Studies have not demonstrated that lemonade causes a sustained improvement of urine pH, increased citric acid concentration in urine, reduction in supersaturation by stone-forming salts, or prevention of recurrent stones.


title: South Florida

text: South Florida is the southernmost region of the U.S. state of Florida. It is one of Florida's three most commonly referred to directional regions; the other two are Central Florida and North Florida. South Florida is the southernmost part of the continental United States and the only region of the continental U.S. that includes some areas with a tropical climate.


title: South Florida

text: South Florida is dominated by the Miami metropolitan area and the Everglades, and contains the Florida Keys, three U.S. national parks (namely Biscayne, Dry Tortugas, and Everglades), and multiple cities. While the term most commonly refers to the Keys and Greater Miami, interpretations vary on the inclusion of some other parts of Florida within the South Florida region, most commonly the southern parts of the Tampa Bay area, the inclusion of Southwest Florida and its cities, and the Treasure Coast.


title: South Florida

text: As with all vernacular regions, South Florida has no official boundaries or status and is defined differently by different sources. A 2007 study of Florida's regions by Ary Lamme and Raymond K. Oldakowski found that Floridians surveyed identified "South Florida" as comprising the southernmost sections of peninsular Florida, meaning from Jupiter, Florida, southward. That area includes the Miami metropolitan area (defined as Miami-Dade, Broward, and Palm Beach counties), the Florida Keys, and the interior region known as the Glades. Additionally, Southwest Florida, representing the state's southern Gulf Coast, has emerged as a directional vernacular region. Some respondents from as far northwest as the southern Tampa Bay area identified their region as being in South Florida rather than Southwest or Central Florida. Confusing the matter further, the University of South Florida, named in part because of its status as the state's southernmost public university at the time of its 1957 founding, is located in Tampa. Florida State Road 70 bisects approximately the southern third of Florida from west to east.


title: South Florida

text: Enterprise Florida, the state's economic development agency, identifies "Southeast Florida" as one of eight economic regions used by the agency and other state and outside entities, including the Florida Department of Transportation. Some entities alternately designate this region "South Florida". Its definition includes much of the same territory as Lamme and Oldakowski's report (except the Gulf Coast and much of the interior Glades region) as well as additional area. It includes Monroe County (the Keys) and the three metropolitan counties of Miami-Dade, Broward, and Palm Beach, as well as the three "Treasure Coast" counties of Indian River, St. Lucie, and Martin to the north.


title: South Florida

text: South Florida is politically diverse, with multiple congressional districts in the region supporting both the Democratic and Republican parties. As evidenced by the 2020 United States presidential election, supporters of the Democratic Party are mostly concentrated in urban areas, as well as areas to the west of and including downtown Key West, rural communities surrounding Immokalee, and the areas surrounding Belle Glade, while supporters of the Republican Party reside in the most costal regions of the Miami area north of Pompano Beach, most of the Everglades, most of the regions between Port St. Lucie and Riviera Beach, Southwest Florida, and a supermajority of the region's inland and rural areas.


title: South Florida

text: The Miami accent is a regional accent of the American English dialect spoken in South Florida, particularly in Miami-Dade, Broward, Palm Beach, and Monroe counties. The accent was born in central Miami, but has expanded to the rest of South Florida in the decades since the 1960s. The Miami accent is most prevalent in American-born South Floridian youth.


title: South Florida

text: The Miami accent is based on a fairly standard American accent but with some changes very similar to dialects in the Mid-Atlantic (especially the New York area dialect, Northern New Jersey English, and New York Latino English.) Unlike Virginia Piedmont, Coastal Southern American, and Northeast American dialects, the "Miami accent" is rhotic; it also incorporates a rhythm and pronunciation heavily influenced by Spanish (wherein rhythm is syllable-timed).


title: South Florida

text: Lamme and Oldakowski identify several demographic, political, and cultural elements that characterize South Florida and distinguish it from other areas of the state. Many of its differences appear to be driven by its proportionately higher level of migration from the northern U.S. states and from the Caribbean and Latin America, particularly in the densely populated Miami area. Politically, South Florida is more liberal than the rest of the state. While less than 10% of people in either North or Central Florida felt their area was liberal, over a third of South Floridians described their region as such. 38% characterized the area as conservative; 26% as moderate. This tracks with South Florida's demographics, and Lamme and Oldakowski's findings parallel Barney Warf and Cynthia Waddell's research on Florida's political geography during the 2000 Presidential election. The economy in South Florida is very similar to that in Central Florida. Compared to the more diversified economy in North Florida, tourism is by far the most significant industry in South and Central Florida, with a much smaller but vibrant agricultural industry.


title: South Florida

text: Lamme and Oldakowski's survey also found some cultural indicators distinguishing South Florida. South Florida is the only region of the state where ethnic foods are as popular as general American cuisine. Floribbean cuisine is a fusion cuisine which developed in South Florida, drawing influence from Floridian, Caribbean, Asian and Latin American cuisines. Additionally, while there was little geographical variation for most styles of music, there was regional variation for both country and Latin music. Country was significantly less popular in South Florida than in North or Central Florida, while Latin was more popular than in the other regions.


title: South Florida

text: The Anthony J. Catanese Center for Urban and Environmental Solutions at Florida Atlantic University notes the unusual growth pattern of South Florida. Unlike many areas with centralized cities surrounded by development, most of South Florida is preserved natural area and designated agricultural reserves, with development restricted to a dense, narrow strip along the coast. The developed area is highly urbanized and increasingly continuous and decentralized, with no particular dominant core cities. The center projects this pattern to continue in the future.


title: South Florida

text: Over time, there have been numerous proposals for partitioning the state of Florida to form a separate state of South Florida. Such proposals have usually been made as political statement rather than serious attempts at secession. Reasons often stated are cultural, ethnic, economic, and financial frustrations with the state government in Tallahassee, which is in North Florida.


title: South Florida

text: In 2008, the North Lauderdale City Commission passed a resolution calling for a new state of South Florida to be formed from Palm Beach, Broward, Miami-Dade and Monroe Counties.


title: South Florida

text: In 2014, the City of South Miami passed a resolution in favor of splitting the state in half, with a northern boundary drawn to include the counties of Brevard, Orange, Polk, Hillsborough, and Pinellas (roughly the Tampa Bay and Orlando areas). In total, the proposed State of South Florida would have included 24 counties.


title: Ramsar Convention

text: The Ramsar Convention on Wetlands of International Importance Especially as Waterfowl Habitat is an international treaty for the conservation and sustainable use of Ramsar sites (wetlands). It is also known as the Convention on Wetlands. It is named after the city of Ramsar in Iran, where the convention was signed in 1971.


title: Ramsar Convention

text: Every three years, representatives of the contracting parties meet as the Conference of the Contracting Parties (COP), the policy-making organ of the convention which adopts decisions (resolutions and recommendations) to administer the work of the convention and improve the way in which the parties are able to implement its objectives. COP12 was held in Punta del Este, Uruguay, in 2015. COP13 was held in Dubai, United Arab Emirates, in October 2018.


title: Ramsar Convention

text: The list of wetlands of international importance included 2,331 Ramsar sites in May 2018 covering over . The countries with most sites are the United Kingdom with 175 and Mexico with 142. The country with the greatest area of listed wetlands is Bolivia, with around .


title: Ramsar Convention

text: The Ramsar Sites Information Service (RSIS) is a searchable database which provides information on each Ramsar site.


title: Ramsar Convention

text: As of 2016 there are 18 transboundary Ramsar sites, and 15 Ramsar regional initiatives covering regions of the Mediterranean, Asia, Africa, and South America.


title: Ramsar Convention

text: The Ramsar Convention works closely with six other organisations known as international organization partners (IOPs). These are:


title: Ramsar Convention

text: These organizations support the work of the convention by providing expert technical advice, helping implement field studies, and providing financial support. The IOPs also participate regularly as observers in all meetings of the conference of the parties and as full members of the Scientific and Technical Review Panel.


title: Ramsar Convention

text: This is the convention's governing body consisting of all governments that have ratified the treaty. This ultimate authority reviews progress under the convention, identifies new priorities, and sets work plans for members. The COP can also make amendments to the convention, create expert advisory bodies, review progress reports by member nations, and collaborate with other international organizations and agreements.


title: Ramsar Convention

text: The Standing Committee is the intersessional executive body which represents the COP between its triennial meetings, within the framework of the decisions made by the COP. The contracting parties that are members of the Standing Committee are elected by each meeting of the COP to serve for the three years.


title: Ramsar Convention

text: The Scientific and Technical Review Panel (STRP) provides scientific and technical guidance to the Conference of Contracting Parties, the Standing Committee, and the Ramsar Secretariat.


title: Ramsar Convention

text: The Secretariat carries out the day-to-day coordination of the convention's activities. It is based at the headquarters of the International Union for Conservation of Nature (IUCN) in Gland, Switzerland.


title: Ramsar Convention

text: The implementation of the Ramsar Convention is a continuing partnership between the Conference of Contracting Parties, the Standing Committee, and the Secretariat, with the advice of the subsidiary expert body, the Scientific and Technical Review Panel (STRP), and the support of the international organization partners (IOPs).


title: Ramsar Convention

text: February 2 is World Wetlands Day, marking the convention's adoption on 2 February 1971. Established to raise awareness about the value of wetlands for humanity and the planet, WWD was celebrated for the first time in 1997, and has grown since then. In 2015 World Wetlands Day was celebrated in 59 countries.


title: Ramsar Convention

text: The convention was co-founded by Eskandar Firouz (former environment minister of Iran), Luc Hoffmann of Tour du Valat research station in the Camargue in France, and Geoffrey Matthews of the Wildfowl & Wetlands Trust at Slimbridge in the late 1960s. The conference which adopted the terms of the agreement was held in the Iranian Caspian Sea resort of Ramsar on 2 February 1971. The convention turned 50 in 2021.


title: Nicholas Tse

text: Nicholas Tse Ting-fung (born 29 August 1980) is a Hong Kong actor, martial artist, singer, songwriter, entrepreneur and chef. As multi talented celebrity, he became a TV chef and food critic in 2014.


title: Nicholas Tse

text: Tse initially entered the entertainment industry in 1996 as a singer. He learned martial arts from Philip Ng, Andy On, and Sammo Hung, stunts from Jackie Chan, and martial arts for the screen and television from Chung Chi Li. Tse made his film debut in 1998 with the crime film "", for which he received the Hong Kong Film Award for Best New Performer for his performance. In 2003, Tse founded Post Production Office Limited, a special effects company in Hong Kong which provides services for movies, video games, and advertisements. The company grossed over one billion Hong Kong dollars, and has since been sold.


title: Nicholas Tse

text: In 2011, he won the Hong Kong Film Award for Best Actor for his performance in the film "The Stool Pigeon", making him the first person ever to have won all of the following three Hong Kong Film awards: Best Actor, Best Supporting Actor and Best New Performer.


title: Nicholas Tse

text: Tse was born in Hong Kong on 29 August 1980 to famous Hong Kong actor Patrick Tse () and actress Deborah Lee (). His younger sister is Jennifer Tse. Tse moved to Vancouver, British Columbia, Canada at eight years old. He attended St. George's School, Vancouver, but moved with his family to Hong Kong. Nicholas later attended Hong Kong International School for one year before dropping out due to low grades in grade 10. For a year he lived in Phoenix, Arizona, but was expelled for his poor academic performance. He studied music in Japan before returning to Hong Kong. He currently holds Hong Kong citizenship after giving up Canadian citizenship as part of the Chinese government crackdown on the entertainment industry.


title: Nicholas Tse

text: In 1995, at age 14, Tse attended a series of concerts at the Hong Kong Coliseum from Faye Wong, who was entering the prime of her career at age 24. He became, in his own words, obsessed with the pop star; the two would become romantic partners decades later. In 1996, Tse was singing at a party for a family friend when he was discovered by Albert Yeung, the head of Emperor Entertainment Group. In 1997, Tse signed a record deal with EEG under the Fitto label and released his first album, "My Attitude". The album was ranked 3rd on the top selling CD chart of IFPI. In the same year of his debut, he won the most popular new artist award.


title: Nicholas Tse

text: Tse achieved mainstream success in 1998 with songs like "早知" (Knew It Would Be Like That) and "如果只得一星期" (If There's Only One Week) and became a prominent heartthrob in the entertainment industry. He received a musical award during the 1999 Jade Solid Gold Top 10 Awards with his popular song "非走不可" (No Choice But To Leave), recorded on 27 September 1993.


title: Nicholas Tse

text: In 2000, Tse released the album with the main hit single "活著 VIVA", which was regarded as his most popular song ever, and furthered his career significantly. After the release of this song, he became widely regarded as an A-list singer. In 2001, he released the album "玉蝴蝶" (Jade Butterfly), which included two hit songs, "玉蝴蝶" and "潛龍勿用".


title: Nicholas Tse

text: In 2002, Tse received the World's Best Chinese Artist award at the 2002 World Music Award for the success of his "Jade Butterfly" album.


title: Nicholas Tse

text: Tse's most notable films have included "" (1998), "Gen-X Cops" (1999), "Time and Tide" (2000), and "Invisible Target" (2007). He also collaborated with Jackie Chan in "New Police Story" (2004). Tse has also acted in romance films including "Tiramisu" (2002) and "Jade Goddess of Mercy" (2003). Late in his career, he ventured into comedic roles in "Enter the Phoenix" (2004), "A Chinese Tall Story" (2005), and "McDull, the Alumni" (2006). In the Hong Kong translated version of "A Bug's Life" (), Tse did the voice dubbing for the character Flik. He also lent his voice to the Chinese animation film "Lotus Lantern" (1999). Tse's performance in "Bodyguards and Assassins" (2009), earned him an Asian Film Award at the 4th Asian Film Awards for Best Supporting Actor, and in 2011, Tse received a Hong Kong Film Award for Best Actor at the 30th Hong Kong Film Awards for "The Stool Pigeon" (2010), beating fellow actors Chow Yun-fat, Jacky Cheung, Tony Leung Ka-fai, and Nick Cheung. Tse had a love for martial arts at a young age, but he formally learned martial arts for the screen from stunt leader Jackie Chan and Chung Chi Li for films such as, Gen-X-Cops and Invisible Target. He worked with "Donnie Yen" for martial arts film, Dragon Tiger Gate. He still practices martial arts for the screen and exercise. He's also a Wing Chun practitioner, being trained by fellow co-star and friend Philip Ng alongside co-star and friend Andy On.


title: Nicholas Tse

text: Tse has starred in two TVB Hong Kong local dramas, "Aiming High" () and (). He also participated in a documentary produced by Television Broadcasts Limited called "On the Road II " (), made in Cambodia in 2007. The rest of his drama series were filmed and produced by companies in Mainland China. Most of Tse's dramas are wuxia series, a genre of fantasy Chinese fiction concerning the adventures of martial artists in ancient China.


title: Nicholas Tse

text: On 12 January 2006, wax statues of Tse were first exhibited along with seven other well known Chinese figures including basketball star Yao Ming, and Jackie Chan at the Madame Tussauds in London. On 19 June 2006, wax statues of both Tse and his then wife Cecilia Cheung were revealed in Shanghai exhibition in Shanghai.


title: Nicholas Tse

text: Most of Tse's songs were based on the Cantopop rock genre such as some of his top hits ""front, back, left, right"" (前前後後左左右右), ""Exposure"" (曝光), and ""Lonely Base"" (寂寞堂口). Some of his songs were produced in Tse's own 'Nic Production', which was revealed in several TVB interviews. Tse featured his flame guitar and a flamethrower in the music video of his widely popular song and one of his most classical pop rock songs, ""Live Viva"" (活著 VIVA).


title: Nicholas Tse

text: He has sung a number of duets with fellow Cantopop singers, namely ""Love"" (愛) with Charlene Choi, ""Second Life"" (第二世), ""Amen"" (阿門) both with Joey Yung, ""Kid"" (細路) with Eason Chan, ""You Can't Stop Me"" with Sam Lee and Stephen Fung, and "Beauty and the Beast" with Meilin.


title: Nicholas Tse

text: Besides being a singer, Tse has shown his interest and talent in songwriting. Plenty of his songs were produced by himself, either of the lyrics or the melody or both. For example, Tse composed and arranged the melodies for his most renowned Mandarin songs, ""I love you because I love you"" (因為愛所以愛) and ""Huang Zhong Ren"" (黃種人). Tse also participated in the creation of lyrics in ""Huang Zhong Ren"".


title: Nicholas Tse

text: Tse began the process of renouncing his Canadian citizenship in September 2021. He had acquired dual Hong Kong-Canadian citizenship after moving to Canada in his youth.


title: Nicholas Tse

text: Tse began a relationship with musician Faye Wong, 11 years his senior, in the late 1990s. They broke up in 2002.


title: Nicholas Tse

text: On 31 July 2006, Tse confirmed that he was dating actress Cecilia Cheung in an interview with Hong Kong commercial radio station 881/903. On 29 September 2006, Tse was photographed with his wedding ring at the Hong Kong International Airport, announcing that he and Cecilia Cheung married in a secret wedding ceremony in Pamalican, Philippines. They have two sons: Lucas, born on 2 August 2007, and Quintus, born on 12 May 2010. On 14 June 2011, Tse reportedly filed for divorce from Cheung.


title: Nicholas Tse

text: In 2014, it was reported that Tse had rekindled his relationship with Faye Wong, who had divorced her second husband in 2013. As of 2020, Tse and Faye Wong continue to reside together.


title: Nicholas Tse

text: In the early morning of 23 March 2002, Tse crashed his Ferrari 360 Modena in Hong Kong Central. Initially, it was claimed that his driver was responsible for the crash, but further investigation by the ICAC revealed that the story was fabricated, involving three other men and a police officer. Officer Lau Chi-Wai was sentenced to six months in prison. Tse spent two weeks in prison and was sentenced to 240 hours of community service for obstruction of justice. The 240 hours portion of his sentence was the maximum punishment for this offence, given that Tse was a young offender at the time (21 years and 7 months). This incident had caused him to have a downfall in popularity. Tse had said that money to him has gone down


title: Nicholas Tse

text: by 40% since the accident. The car was originally a gift from the company EEG, as Tse himself accounted for 56% of the revenue.


title: Nicholas Tse

text: Tse has had his share of brush-ups with "paparazzi". A photographer of "Sudden Weekly" magazine accused Tse of hitting him outside a restaurant in Taiwan, bruising his nose and elbow. Although Tse denied the assault charge, there was a settlement in July 2002.


title: Nicholas Tse

text: Tse had another accident in 2003, where he crashed his Toyota Camry into Wan Chai train station. He was banned from driving for six months and fined HK$4000 for reckless driving. Prior to this incident, he was fined HK$7000 and had his license suspended for a year because he had two separate charges for speeding.


title: Nicholas Tse

text: He later had another accident in November 2005, where he collided with a Public Security Bureau Bus in an Audi RS4 in Lantau. He was banned from driving for another six months and fined HK$4,000, again for reckless driving. After this police charge, Tse released the album "Reborn."


title: Nicholas Tse

text: In February 2008, Tse's wife, Cecilia Cheung, was caught up in the Edison Chen photo scandal, when intimate photographs of her were widely distributed on the internet.


title: Nicholas Tse

text: On 28 October 2016, Tse was honoured as the first ever "Friend of Michelin", awarded for Michelin-star-worthy non-professional chefs and restaurateurs. On 30 November 2017, he prepared the dessert course for A Night Among the Stars, a seven course gala dinner with Michelin-star chefs Alain Ducasse, Kwong Wai-keung, Tam Kwok-fung, Fabrice Vulin, Hidemichi Seki, and Noah Sandoval.


title: Assassin's Creed III: Liberation

text: Assassin's Creed III: Liberation is a 2012 action-adventure video game developed by Ubisoft Sofia and published by Ubisoft. It was originally released for the PlayStation Vita on October 30, 2012, in North America, with a worldwide launch the following day. It is the fourth spin-off installment in the "Assassin's Creed" series, and takes place alongside the events of "Assassin's Creed III".


title: Assassin's Creed III: Liberation

text: The plot is set within a fictional history of real-world events and follows the millennia-old struggle between the Assassins, who fight to preserve peace and free will, and the Templars, who desire peace through control. The game is set in late 18th-century French Louisiana, from 1765 to 1777, and focuses on the life of French Assassin Aveline de Grandpré, the series' first female protagonist, as she fights the Templars' attempts to gain control of New Orleans following the end of the French and Indian War. The game takes place within an open world and is presented from the third-person perspective with a primary focus on using Aveline's combat, stealth, and parkour abilities to complete missions and explore the environment.


title: Assassin's Creed III: Liberation

text: The original release of "Liberation" received mixed reviews from critics, who praised its setting and protagonist, but disliked the narrative's execution and certain aspects of the gameplay, while feeling that the title was limited by its status as a spin-off. A fully remade version of the game, titled Assassin's Creed: Liberation HD, was released in January 2014 for the PlayStation 3, Xbox 360 and Microsoft Windows via the PlayStation Network, Xbox Live Arcade and Steam, respectively. A remastered version of "Liberation HD" was released as part of "Assassin's Creed III Remastered" for Xbox One, PlayStation 4, and Windows in March 2019, for the Nintendo Switch in May 2019, and for Google Stadia in December 2021. The remastered version was redesigned to operate with 4K HDR/enhanced visuals, and includes several improvements such as a new graphics engine using physics-based lighting, new character models, and heavily revamped gameplay mechanics.


title: Assassin's Creed III: Liberation

text: "Assassin's Creed III: Liberation" retains the "franchise's trademark open world and gameplay", while making use of the PlayStation Vita's touchscreen and rear touch pad, cameras and gyroscope. Players assume the role of Assassin Aveline de Grandpré in 18th-century French Louisiana, who controls similarly to other protagonists in the series, being able to free run, use 'social stealth', and fight enemies using a counter-based combat system. Because the game uses the same engine as "Assassin's Creed III", most of the animations from that game are reused. However, Aveline does have several unique animations, as well as the ability to dual-wield weapons, such as the new blowpipe as well as the familiar swords, knives, pistols and hidden blade.


title: Assassin's Creed III: Liberation

text: New gameplay mechanics exclusive to "Liberation" include a Chain Kill ability, which allows Aveline to chain attacks together to kill multiple enemies at once; a trade system, in which Aveline manages her father's trade network by purchasing goods and selling them to other cities via ship; and the ability to switch between Aveline's three distinct personas, each providing its own advantages and disadvantages. For example, the Assassin persona performs better in combat, but is very quickly detected by enemies; the Slave persona can blend in with other slaves or carry crates to pass by suspicious enemies, but has access to fewer weapons; and the Lady persona can charm or bribe guards to enter restricted areas and is detected slower than the other personas, but cannot free run.


title: Assassin's Creed III: Liberation

text: By linking the game to "Assassin's Creed III", players can receive several in-game bonuses, such as the signature tomahawk of "Assassin's Creed III"'s protagonist, , an exclusive character skin, a multiplayer character and a complete upgrade of all ammunition pouches.


title: Assassin's Creed III: Liberation

text: The multiplayer component, exclusive to the original PlayStation Vita version, consists of players tapping nodes on a map, using characters (represented with static portraits) to capture bases and collect supplies, among other things. This differs from the series usual competitive multiplayer which had players assassinating each other for sport.


title: Assassin's Creed III: Liberation

text: "Liberation" explores the life of a second 18th-century assassin in Colonial America who operated during the end of the French and Indian War within Louisiana, during its Spanish occupation; an Afro-French woman named Aveline de Grandpré, whose work included freeing slaves while eradicating Templar presence in New Orleans. Aveline's story encompasses a period of twelve years of her life, and takes place alongside the events of "Assassin's Creed III". Much of the game takes place within the city of New Orleans and the bayou that surrounds it, though also includes locations connected to the Seven Years' War and the American Revolutionary War.


title: Assassin's Creed III: Liberation

text: "Liberation" incorporates several events from American history into its plot, like the tragic mulattos, the anti-miscegenation laws in the United States, the back-to-Africa movement, and education during the Slave Period. Historical characters featured in the game include Jean-Jacques Blaise d'Abbadie, Antonio de Ulloa, François Mackandal, and Gilbert Antoine de Saint-Maxent.


title: Assassin's Creed III: Liberation

text: In the modern day, Abstergo Entertainment, a subsidiary of Abstergo that produces multimedia goods, releases their first major product, "Liberation" - a video game about the life of the Assassin Aveline de Grandpré. The hacker group Erudito contacts the player during their playthrough, and reveals that a heavy amount of censoring was done in regard to the Assassin-Templar war, offering to help them learn the truth.


title: Assassin's Creed III: Liberation

text: The player begins experiencing the life of Aveline in 1765, as she operates within the city of New Orleans from her family mansion, which she lives in alongside her father, Philippe Olivier de Grandpré, and stepmother, Madeleine de L'Isle. As the city undergoes a transition of control from France to Spain near the end of the French and Indian War, Aveline discovers a plot to control Louisiana, orchestrated by the Templar Rafael Joaquín de Ferrer. To counter this, she assassinates two men assisting in his goals—French governor Jean-Jacques Blaise d'Abbadie and an Assassin turncoat named Baptiste. A year after these assassinations, de Ferrer leaves New Orleans, while his associate Antonio de Ulloa is appointed Louisiana's new Spanish governor.


title: Assassin's Creed III: Liberation

text: In 1768, Aveline's mentor Agaté orders her to assassinate Ulloa, who has been imposing strict trading restrictions, setting up a covert slave-trading operation, and allowing French officials to continue operating in the city. However, Aveline spares Ulloa upon learning the slaves sent out of the city were assigned to a Templar excavation site in Chichén Itzá, and instead orders him to step down as governor and leave New Orleans. Against Agaté's orders, Aveline heads to Chichén Itzá disguised a slave, and runs into her mother Jeanne, a former Assassin who disappeared during her youth. She also encounters de Ferrer, and learns that he has been ordered by his superior, known only as the "Company Man", to use the slaves to find an ancient chamber built by the First Civilization. Aveline enters the chamber, retrieving one half of an artifact called the Prophecy Disk, and kills de Ferrer. Jeanne, fearing that Agaté sent Aveline to kill her for betraying the Assassins, warns her daughter not to give him the Disk.


title: Assassin's Creed III: Liberation

text: In 1771, following Aveline's return to New Orleans, her friend and fellow Assassin Gérald Blanc informs her that while Spanish control strengthened during her absence, a Templar named Diego Vázquez bribed several soldiers to control the Bayou. Learning that Agaté is in danger, Aveline goes to warn and protect him. A year later, she returns to Chichén Itzá, where she reunites with Jeanne and forgives her for her past actions. After helping Aveline recover the second half of the Disk, Jeanne stays behind to protect the area from further Templar incursions. In 1776, Aveline returns to New Orleans and commits herself to freeing slaves. When Madeleine learns of her stepdaughter's work, she asks her to help a former slave, George Davidson, escape to the north so that he may join the Patriot army. Aveline later assassinates Vázquez, but learns that the he is not the Company Man as she assumed. During this time, Philippe mysteriously falls ill and dies.


title: Assassin's Creed III: Liberation

text: In 1777, Gérald informs Aveline of a Loyalist officer operating at the New York Frontier who might know the Company Man's identity. With the help of fellow Assassin Connor, Aveline kills the officer, revealed to be Davidson. After returning to New Orleans and deducing that Madeleine is the Company Man and poisoned Philippe, Aveline confronts her. Madeleine reveals that she had been secretly grooming Aveline to become a Templar, and asks her to kill Agaté as a final show of trust. Aveline goes to warn him, but Agaté, believing that Aveline has already joined the Templars because of her past disobediences, attacks her, before committing suicide, unable to accept his failure as a mentor.


title: Assassin's Creed III: Liberation

text: Aveline meets with Madeleine at the St. Louis Cathedral to be initiated into the Templar Order, and gives her the Prophecy Disk. Madeleine is unable to activate it, and deduces that it is missing its final component: a locket Jeanne had given to Aveline in her youth. Aveline then reveals her true intentions and kills Madeleine and the other attending Templars, before connecting the locket to the Disk. This unlocks a holographic recording from the time of the First Civilization, showing the election of Eve as the leader of the human rebellion during the Human-First Civilization War.


title: Assassin's Creed III: Liberation

text: "Assassin's Creed III: Liberation" was released on October 30, 2012, the same day as "Assassin's Creed III". The game is available in a PS Vita bundle pack with a new crystal white Wi-Fi Vita and a 4GB memory card. In Japan it was released under the title "Assassin's Creed III: Lady Liberty".


title: Assassin's Creed III: Liberation

text: It was announced on September 10, 2013, that the game would be re-released as "Assassin's Creed: Liberation HD" for PlayStation 3, Xbox 360 and Microsoft Windows via the PlayStation Network, Xbox Live Arcade and Steam, respectively, in 2014. The game features visuals closer to "III" as well as updated audio, AI and facial animations. Additional missions have been added and some of the Vita-specific touch screen missions have been removed, as well as the nodes multiplayer and a minor Quick Time Event minigame. The game was released on the PlayStation 3 on January 14, 2014, in North America and January 15, 2014, in Europe. The Microsoft Windows and Xbox 360 versions were released worldwide on January 15, 2014.


title: Assassin's Creed III: Liberation

text: It was announced on September 13, 2018, that "Assassin’s Creed III Remastered" would be included in the "" season pass. "Assassin's Creed III Remastered" was announced to include all of its original DLC and a remastered version of "Assassin's Creed III: Liberation".


title: Assassin's Creed III: Liberation

text: On July 11, 2022, "Assassin's Creed: Liberation HD" was removed from purchase on Steam. Furthermore, it was announced that all DLC and online features would subsequently be inaccessible to players after September 1, 2022.


title: Assassin's Creed III: Liberation

text: Purchasing "Assassin's Creed III" for the PlayStation 3 gives the player the ability to connect it to "Liberation" and unlock an exclusive mission in the latter game featuring Connor, as well as a multiplayer skin and an Ammunition Pouch. There was also a promotional DLC, titled "Mysteries of the Bayou Pack", that came with pre-orders of the game in PAL regions. It included an exclusive weapon, an alligator hunting hat, a multiplayer skin, and Ammunition Pouches for smoke bombs and poison darts.


title: Assassin's Creed III: Liberation

text: All the additional content is included in "Liberation HD" and "Liberation Remastered", save for the multiplayer skin, as that feature was removed.


title: Assassin's Creed III: Liberation

text: The music in the game was composed by Winifred Phillips and produced by Winnie Waldron. The soundtrack album was released by Ubisoft Music on the same day as the release of the "Assassin's Creed III: Liberation" video game, October 30, 2012. Together with music producer Winnie Waldron, Winifred Phillips won several awards for her work on this project. For the music composition of the Assassin's Creed III Liberation video game, Phillips won a Global Music Award for musical excellence. Composer Winifred Phillips and music producer Winnie Waldron won a 2012 Hollywood Music in Media Award for the music score for "Assassin's Creed III: Liberation." The main theme music of the Assassin's Creed III: Liberation video game won a G.A.N.G. Award from the Game Audio Network Guild in the category of "Best Original Vocal Song — Choral."' The music of "Assassin's Creed III Liberation" won a GameFocus Award for Best Music of 2012. The game's musical score also received nominations in several year-end award competitions, including the GameZone Awards, the Best of IGN Awards, and the G4TV X-Play Best of 2012 Awards.


title: Assassin's Creed III: Liberation

text: The music of "Assassin's Creed III Liberation" was very well received by both game and music critics. Robert Workman of GameZone wrote, "The music is superb," and Evan Narcisse of Kotaku called the soundtrack, "a stealthy success." Jen Bosier of VideoGameWriters said that the music of "Assassin's Creed III Liberation" was "without question, the best soundtrack the series has seen to date." Music critic Randall Larson of BuySoundtrax.com stated, "This is a fine score and one that even non-gamers should applaud for its cinematic, dynamic and immersive drive." Reviewer Lucas Smith of Piki Geek asserted that "the soundtrack will go down as one of the year's best."


title: Assassin's Creed III: Liberation

text: Initial reviews for "Assassin's Creed III: Liberation" were mixed. Metacritic, which assigns a score based on reviews from industry leaders, has the game scored at 70/100 based on 71 reviews, indicating "mixed or average reviews".


title: Assassin's Creed III: Liberation

text: Shaun McInnis, reviewer for GameSpot, gave the game a score of 6.5/10, praising the protagonist as "...a woman born from the romance between a wealthy father and a slave mother, someone who has overcome her uncertain upbringing to find a new life in the Assassin Brotherhood". McInnis also commended the setting, writing "...a brilliant version of 18th-century New Orleans, one that beautifully reflects the diverse cultural ambience formed over years of operating as a French trading port". However, he also wrote that the game "squanders its most unique ideas...Liberation takes little advantage of its own narrative format" and that the plot is "largely aimless and hastily delivered".


title: Assassin's Creed III: Liberation

text: IGN's Greg Miller stated, "The moves and kills you'd expect are here, but the story is boiled down to be easy to jump in and out of. That takes away some of the excitement in playing through it", giving it 7.2/10. In April 2020, "Game Informer" ranked the game as the 13th best game in the "Assassin's Creed" series to date, the lowest entry on the list.


title: Brian Armstrong (businessman)

text: Brian Armstrong (born January 25, 1983) is an American business executive, billionaire and investor who is CEO of cryptocurrency platform Coinbase. He received media attention for his policy of keeping the workplace free of political activism.


title: Brian Armstrong (businessman)

text: Armstrong was born on January 25, 1983, near San Jose, California; both of his parents were engineers. During his years in high school he attended Bellarmine College Preparatory, a Catholic, all-male, private secondary school. Armstrong attended Rice University in Texas, and earned a dual bachelor's degree in economics and computer science in 2005, followed by a master's in computer science in 2006. While at Rice, he started a business matching tutors to students, and after graduating, spent a year in Buenos Aires while working for an education company. While in Buenos Aires, he saw firsthand the effects of inflation that were affecting Argentina at the time.


title: Brian Armstrong (businessman)

text: Armstrong's early career included working as a developer for IBM and consultant at Deloitte. In 2010, he came across the Bitcoin white paper published under the alias Satoshi Nakamoto. In 2011, he joined Airbnb as a software engineer, and was exposed to payment systems in the 190 countries Airbnb operated in at the time. While at Airbnb, he saw the difficulties of sending money to South America. He began working weekends and nights to write code in Ruby and JavaScript to buy and store cryptocoins. In 2012, he entered the Y Combinator startup accelerator and received a $150,000 investment, which he used to fund Coinbase.


title: Brian Armstrong (businessman)

text: His post on Hacker News looking for a co-founder to get into the Y Combinator program later became a viral post in Hacker News. He eventually met his co-founder Fred Ehrsam on a reddit subgroup and is quoted to have done fifty plus dates to find that perfect co-founder.


title: Brian Armstrong (businessman)

text: In 2012, Armstrong and Fred Ehrsam co-founded Coinbase, as a way for cryptocurrency enthusiasts to trade bitcoins and other digital currencies. Armstrong was its first CEO. A 2018 funding round valued the company at $8.1 billion, and in December 2020, the company filed with the SEC to go public through a direct listing. Following a direct listing in April 2021, Coinbase's market capitalization rose to $85B, and according to Forbes, , Armstrong has a net worth of $2.4 billion.


title: Brian Armstrong (businessman)

text: He was featured in the 2020 nonfiction book "Kings of Crypto: One Startup's Quest to Take Cryptocurrency Out of Silicon Valley and Onto Wall Street".


title: Brian Armstrong (businessman)

text: Armstrong self-funded and founded the scientific research site ResearchHub, modeled on the GitHub code repository, as a way of making research papers available to the public.


title: Brian Armstrong (businessman)

text: Armstrong wrote a blog post in September 2020 calling Coinbase a "Mission Focused Company", discouraging employee activism and discussion of political and social issues at work. He offered severance packages for Coinbase employees uncomfortable with this policy; as a result, sixty employees (amounting to 5% of the company) left Coinbase. Prior to this, Armstrong supported the Black Lives Matter movement and tweeted when George Floyd was murdered: "I've decided to speak up. It's a shame that this even needs to be said in this day and age, but racism, police brutality, and unequal justice are unequivocally wrong, and we need to all work to eliminate them from society."


title: Brian Armstrong (businessman)

text: In 2021, "Forbes" named Armstrong #1 on its Crypto Rich List, with an estimated net worth of $6.5 billion as of February 2021. He was also listed 60th on the Forbes 400 list of the richest people in America.


title: Brian Armstrong (businessman)

text: In 2018, Armstrong was the first cryptocurrency executive to sign the Giving Pledge, when he pledged to give away the bulk of his wealth to philanthropic causes. He also set up a philanthropic effort called GiveCrypto.org, to allow people to make public or anonymous donations to help others living in poverty.


title: The Beat (British band)

text: The Beat (known in the United States and Canada as the English Beat and in Australia as the British Beat) are a British band formed in Birmingham, England, in 1978. Their music fuses Latin, ska, pop, soul, reggae and punk rock.


title: The Beat (British band)

text: The Beat, consisting of Dave Wakeling (vocals, guitar), Ranking Roger (vocals), Andy Cox (guitar), David Steele (bass), Everett Morton (drums), and Saxa a.k.a. Lionel Augustus Martin (saxophone), released three studio albums in the early 1980s: "I Just Can't Stop It" (1980), "Wha'ppen?" (1981) and "Special Beat Service" (1982), and a string of singles, including "Mirror in the Bathroom", "Save It for Later", "I Confess", "Too Nice to Talk To", "Can't Get Used to Losing You", "Hands Off...She's Mine", and "All Out to Get You".


title: The Beat (British band)

text: The Beat formed in Birmingham, England, in 1978, during a period of high unemployment and social upheaval in the United Kingdom. Ranking Roger, one of the band's vocalists, added a Jamaican vocal flavour to the band's sound with his toasting style. Jamaican saxophonist Saxa added a Jamaican ska instrumental sound. Saxa (born Lionel Augustus Martin in 1930) had played saxophone with Prince Buster, Laurel Aitken, and Desmond Dekker in the first wave of ska. He joined the Beat to record their first single, "Tears of a Clown", a cover version of the Motown hit by Smokey Robinson and the Miracles.


title: The Beat (British band)

text: Notable singles from the first album included "Can't Get Used to Losing You", "Mirror in the Bathroom", "Hands Off...She's Mine" and "Best Friend". The second Beat album, "Wha'ppen?" was supported by extensive touring, including a United States tour with the Pretenders and Talking Heads. The album yielded more UK hits, with "All Out to Get You", "Drowning" and "Doors of Your Heart", all of which broke into the Top 40 of the UK Singles Chart. The Beat received support from modern rock radio stations such as KROQ-FM in Los Angeles, the now-defunct KQAK The Quake 99FM (98.9) in San Francisco and KYYX in Seattle.


title: The Beat (British band)

text: Although the Beat's main fan base was in the UK, the band was also popular in Australia, partly due to exposure on the radio station Triple J and the TV show "Countdown". The Beat had a sizable following in the US and Canada, where the band were known as "the English Beat" for legal reasons (to avoid confusion with the American band the Beat). The Beat toured the world with well-known artists including David Bowie, the Clash, the Police, the Pretenders, R.E.M., the Specials and Talking Heads. Members of the band often collaborated on stage with the Specials.


title: The Beat (British band)

text: During their early career, the band were associated with Birmingham-based cartoonist Hunt Emerson, who designed their 'Beat Girl' icon and painted the mural that was used on the cover of "Wha'ppen?"


title: The Beat (British band)

text: After the break-up of the Beat in 1983, Dave Wakeling and Ranking Roger went on to form General Public and had a couple of hit singles in the US and Canada including "Tenderness", while Andy Cox and David Steele formed Fine Young Cannibals with vocalist Roland Gift from the ska band Akrylykz. Drummer Everett Morton and Saxa formed the International Beat along with the Birmingham-based singer, Tony Beet, and the band released an album titled "The Hitting Line" on Blue Beat Records in 1990 (BBSLP 009). The album was produced by Ranking Roger and he often guested with the band at some of their shows. The International Beat toured the UK and United States before calling it a day in 1992. Ranking Roger also briefly joined Mick Jones' post-Clash band Big Audio Dynamite and performed at several live shows with the band. However, the band broke up shortly after he joined when its last album was shelved by the record company. Meanwhile, "March of the Swivelheads", an instrumental version of the Beat's song "Rotating Head", was used in the climactic chase scene of 1986's "Ferris Bueller's Day Off"; the band was listed in the end credits as "The (English) Beat". "Save It for Later" was featured on the soundtrack album to 1996's "Kingpin", 2010's "Hot Tub Time Machine" and 2017's "".


title: The Beat (British band)

text: Everett Morton formed Beat Goes Bang and recruited vocalist Ross Lydon from 360, bass player Faisal Rashid, and Lukasz Machometa on sax, former member of Citybeats and Urban Groove Syndicate.


title: The Beat (British band)

text: Roger released his solo debut, a reggae-oriented album entitled "Radical Departure", in 1988. In the early 1990s, Roger joined members of the Specials to form Special Beat, which toured and released two live albums. They supported the Campaign for Nuclear Disarmament (CND). In 2001, Roger released another solo album, "Inside My Head", which included traditional reggae and ska with influences of electronica, jungle and dub. Ranking Roger's son, Ranking Junior, has followed in his father's footsteps. In 2005, he appeared on the Ordinary Boys' single "Boys Will Be Boys" and is a current member of the Beat in the UK.


title: The Beat (British band)

text: Pete Townshend performed the song "Save It for Later" numerous times between 1985 and 1998. The Who performed the song twice on their 1989 Reunion Tour.


title: The Beat (British band)

text: The Wonder Stuff also played "Save It for Later" featuring Ranking Roger on their "From the Midlands with Love" series in June 2012


title: The Beat (British band)

text: Pearl Jam also began playing "Save It for Later" in 1996 blending it into the end of "Better Man", and it remained in the set list of their 2014 tour.


title: The Beat (British band)

text: In 2003, the Beat's original line-up, minus Cox and Steele, played a sold-out one-off gig at the Royal Festival Hall. In 2004, the VH1 show "Bands Reunited" tried unsuccessfully to reunite the original line-up.


title: The Beat (British band)

text: In 2006, the UK version of the Beat, featuring Ranking Roger, recorded a new album that was mixed by Adrian Sherwood, but it remains unreleased. The band also featured Everett Morton and Mickey Billingham on keyboards, formerly a member of Dexys Midnight Runners and General Public.


title: The Beat (British band)

text: Dave Wakeling fronts the US version of the group as the English Beat, which usually adds a couple of General Public songs to the setlist. The singer and his band flew over to the UK in April 2011, to perform at the London International Ska Festival at the Clapham Grand music venue. They played the Great Dorset Steam Fair show 2011 on 31 August 2011. At this point, both the UK and US versions of the band continued to tour frequently on either sides of the Atlantic.


title: The Beat (British band)

text: In mid-2012, the Beat released a box set, titled "The Complete Beat", comprising their three albums along with non-album singles, remixes and live material. Additional bonus tracks were included on re-released, double-CD versions of each studio album.


title: The Beat (British band)

text: The English Beat recorded two new songs that feature prominently in the Scooby-Doo! Mystery Incorporated episode "Dance of the Undead" which aired 26 March 2013. It features a zombie ska group called Rude Boy and the Ska-Tastics who come back to life in order to turn people into zombies and make them dance to ska music forever. According to an interview Dave Wakeling conducted with the San Francisco Examiner, he said: "This was my first opportunity to do anything for television as a gun for hire, and I actually managed to record and mix two songs in 12 hours. It was like running at double speed with no brakes, but it was exciting, and Warner Bros. really loved them. So the zombies have a song called ‘You’re Dead Right, Mate,’ and the Hex Girls have one called ‘We’re the Good Bad Girls,’ which has a definite Ramones-Runaways vibe to it, but frankly, I'm really happy I did it, because I’ve always loved ‘Scooby-Doo."


title: The Beat (British band)

text: In late 2013, the Beat with Ranking Roger released the live album, "Live in London" which featured a new song titled "How Do You Do (Side to Side)" and also a song previously released solo by Ranking Roger, entitled "Dangerous", among many other songs.


title: The Beat (British band)

text: The Beat feat. Ranking Roger released "Bounce", a studio album, on 30 September 2016, on CD, Vinyl and Digital on DMF Records. The first single from the album, 'Walking on the Wrong Side' was released in July 2016, whilst the album reached No. 49 on the UK Albums Chart.


title: The Beat (British band)

text: In 2018 the Beat feat. Ranking Roger released "The Beat – Live at the Roundhouse" a live album with accompanying DVD, while the (English) Beat starring Dave Wakeling released an album called "Here We Go Love". This album was announced by Wakeling in 2014, with the project funded through the PledgeMusic website (which was a direct-to-fan music platform where fans could donate money to a group to complete an album project).


title: The Beat (British band)

text: On 26 January 2019 the Beat feat. Ranking Roger released a new studio album, "Public Confidential". The first single from the album 'Maniac' was playlisted on BBC Radio 6 Music.


title: The Beat (British band)

text: Weeks after undergoing surgery for two brain tumours, and while undergoing treatment for lung cancer, Ranking Roger died at home on 26 March 2019, aged 56.


title: The Beat (British band)

text: In March 2021, Mini Murphy (Ranking Junior from the Special Beat and the version of the Beat signed to DMF Music in 2016) teamed up with indie rock band the Ordinary Boys to record a tribute to his late father, Ranking Roger. The resulting double-A side single, with "Legacy" on one side and "Jump and Skank" on the other, was released as a download, vinyl and CD single by United Sound Records/Proper.


title: A2 milk

text: A2 milk is a variety of cows' milk that mostly lacks a form of β-casein proteins called A1, and instead has mostly the A2 form. Cows' milk like this was brought to market by The a2 Milk Company and is sold mostly in Australia, New Zealand, China, and the United States. It was sold in the United Kingdom between 2012 and 2019. Non-cow milk, including that of humans, sheep, goats, donkeys, yaks, camels, buffalo, and others, also contain mostly A2 β-casein, and so the term "A2 milk" is also used in that context.


title: A2 milk

text: The a2 Milk Company and some companies producing goat's milk products claim that milk containing A1 proteins is harmful, but there has been no widely accepted scientific work identifying a direct link between A1 protein and any adverse effect on health.


title: A2 milk

text: A1 and A2 beta-casein are genetic variants of the beta-casein milk protein that differ by one amino acid. A genetic test, developed by the a2 Milk Company, determines whether a cow produces A2 or A1 type protein in its milk.


title: A2 milk

text: The European Food Safety Authority (EFSA) reviewed the scientific literature and published their results in 2009. As part of their evaluation, the EFSA looked at the laboratory studies that had been done on bovine β-casomorphin 7 (BCM-7) that found that BCM-7 can act as a weak opioid receptor agonist. The EFSA found no relationship between any disease and drinking milk with the A1 protein. In most of the animal studies, BCM-7 was not administered orally, as humans would be exposed to it, but rather was given to animals by injection into the peritoneal cavity or directly into the spinal cord or brain. The EFSA study emphasized the dangers of drawing conclusions from correlations identified in epidemiological studies and the dangers of not reviewing all the evidence at hand. Reviews conducted in 2005 and 2009 found no demonstration that consuming milk with A1 casein causes diabetes.


title: A2 milk

text: A 2014 review of research into the relationship between consumption of dairy products (including A1 and A2 proteins) and the incidence of diabetes found that while there appears to be a positive correlation between consumption of dairy products by babies and the incidence of type 1 diabetes (T1D), and an inverse relationship between the consumption of dairy products and the development of type 2 diabetes (T2D), these correlations are tentative; it would be very difficult to determine which component or components of milk might be responsible for these effects, and it is unlikely that the expensive and complex research to determine the answers to these questions will ever be conducted.


title: A2 milk

text: A pair of 2020 papers from Purdue University and the University of Auckland suggested that people with lactose intolerance experience significantly fewer symptoms from consuming A2 milk versus regular milk.


title: A2 milk

text: Milk with predominantly A2 protein is not a milk substitute for infants with cow milk protein allergies.


title: A2 milk

text: The a2 Milk Company claims that people who experience discomfort drinking ordinary cows' milk may experience relief when they switch to milk with predominantly A2 protein. This claim is not supported by research.


title: A2 milk

text: In the 1980s, some medical researchers began to explore whether some peptides (including peptides from casein) that are created during digestion might have negative or positive health effects.


title: A2 milk

text: Interest in the distinction between A1 and A2 beta-casein proteins began in the early 1990s via epidemiological research and animal studies initially conducted by scientists in New Zealand, which found correlations between the prevalence of milk with A1 beta-casein proteins in some countries and the prevalence of various chronic diseases. The research generated interest in the media, as well as among the scientific community and entrepreneurs. If it were indeed true that BCM-7 is harming humans, this would be an important public health issue, as well as a commercial opportunity.


title: A2 milk

text: Cow milk is about 87 percent water and 13 percent solids, a combination of fat, carbohydrates in the form of lactose, minerals, and protein. About 30 to 35 percent of the casein (equivalent to two teaspoons per quart of milk) is beta-casein, of which there are several varieties, determined by the genes of the cow. The most common of these variants are A1 and A2 proteins (named for the order in which they were identified by scientists). The sole difference is that one of the 209 amino acids that make up the beta-casein proteins, a proline, occurs at position 67 in the chain of amino acids that make up the A2 beta-casein, while in A1 beta-casein, a histidine occurs at that position. Studies in cells found that digestive enzymes that cut up proteins interact with beta-casein precisely at that location, so that A1 and A2 beta-casein proteins are processed differently. A seven-amino acid peptide, beta-casomorphin-7, can be cut away from the A1-beta-casein protein by those enzymes, but the enzymes cannot cut the A2 protein at that location, so BCM-7 is not formed from A2 proteins. Studies in humans have not consistently found that BCM-7 is formed in the human digestive system. BCM-7 can also be created during the fermentation of milk or through the process by which cheese is made; those same processes can also destroy BCM-7.


title: A2 milk

text: Scientists believe the difference originated as a mutation that occurred between 5,000 and 10,000 years ago—as cattle were being taken north into Europe—when the proline at position 67 was replaced by histidine, with the mutation subsequently spreading widely throughout herds in the Western world through breeding.


title: A2 milk

text: The percentage of the A1 and A2 beta-casein protein varies between herds of cattle, and also between countries and provinces. While African and Asian cattle continue to produce only A2 beta-casein, the A1 version of the protein is common among cattle in the western world. The A1 beta-casein type is the most common type found in cow's milk in Europe (excluding France), the US, Australia and New Zealand. On average, more than 70 percent of Guernsey cows produce milk with predominantly A2 protein, while among Holsteins and Ayrshires between 46 and 70 percent produce milk containing both the A1 and A2 proteins.


title: A2 milk

text: The A2 Corporation was founded in New Zealand in 2000 to commercialise a genetic test to determine whether a cow will produce milk without the A1 protein, and to market the milk it produces as A2 or A2 MILK. In 2003, A2's website said: "Beta casein A1 may be a primary risk factor for heart disease in adult men, and also be involved in the progression of insulin-dependent diabetes in children" and the CEO had linked A1 to schizophrenia and autism. A2 Corporation also petitioned the Food Standards Australia New Zealand regulatory authority to require a health warning on ordinary milk.