First total synthesis of acetylenic alcohol 15-methyltricosa-2,4-diyne-1, 6-diol (strongylodiol-G) derived from marine sponge

<div><p>The first total and efficient synthesis of a naturally occurring acetylenic alcohol 15-methyltricosa-2,4-diyne-1,6-diol (strongylodiol-G) derived from marine sponge involving nine steps has been described. 1-Bromo-9-methyloctadecane (<b>5</b>) and hex-6-tetrahydropyranyloxyhex-2,4-diyn-1-al (<b>9</b>) which were initially synthesised separately starting from 1,8-octanediol (<b>1</b>) and propargyl alcohol (<b>6</b>), respectively, have been used as the final intermediates to obtain the title compound. The key steps in the synthesis involved ionic liquid-mediated bromination of 1,8-octanediol (<b>1</b>), tetrahydropyranylation of 8-bromooctan-1-ol (<b>2</b>) using acidic ionic liquid [bmim]HSO₄ and monotetrahydropyranylation of hex-2,4-yn-1,6-diol (<b>7</b>) using ultrasonic energy.</p></div

Sex Ratio in different Groups.

<p>*<b>Statistically significant difference in proportion.</b></p

The Timing of Drug Funding Announcements Relative to Elections: A Case Study Involving Dementia Medications

<div><p>Background</p><p>Following initial regulatory approval of prescription drugs, many factors may influence insurers and health systems when they decide whether to add these drugs to their formularies. The role of political pressures on drug funding announcements has received relatively little attention, and elections represent an especially powerful form of political pressure. We examined the temporal relationship between decisions to add one class of drugs to publicly funded formularies in Canada's ten provinces and elections in these jurisdictions.</p> <p>Methods</p><p>Dates of provincial formulary listings for cholinesterase inhibitors, which are drugs used to treat Alzheimer's disease and related dementias, were compared to the dates of provincial elections. Medical journal articles, media reports, and proceedings from provincial legislatures were reviewed to assemble information on the chronology of events. We tested whether there was a statistically significant increase in the probability of drug funding announcements within the 60-day intervals preceding provincial elections.</p> <p>Results</p><p>Decisions to fund the cholinesterase inhibitors were made over a nine-year span from 1999 to 2007 in the ten provinces. In four of ten provinces, the drugs were added to formularies in a time period closely preceding a provincial election (<i>P</i> = 0.032); funding announcements in these provinces were made between 2 and 47 days prior to elections. Statements made in provincial legislatures highlight the key role of political pressures in these funding announcements.</p> <p>Conclusions</p><p>Impending elections appeared to affect the timing of drug funding announcements in this case study. Despite an established structure for evidence-based decision-making, drug funding remains a complex process open to influence from many sources. Awareness of such influences is critical to maintain effective drug policy and public health decision-making.</p> </div

Timeline detailing announcements of cholinesterase inhibitor inclusion onto provincial formularies and dates of provincial elections^a.

<p>Abbreviations: L, Liberal; NDP, New Democratic Party; PC, Progressive Conservative; PQ, Parti Quebecois.</p>a<p>Provinces are listed in order of when cholinesterase inhibitors were added to provincial drug formulary. In four provinces (Ontario, Manitoba, Nova Scotia, and Newfoundland and Labrador), announcements of drug formulary coverage were made within the 60-day period preceding a provincial election.</p>b<p>For the time between announcement and closest election, the number of days is given as either the numbers of days preceding an election (a negative number, e.g. −2 days) or the number of days following an election (a positive number, e.g. +73 days).</p>c<p>Minority government.</p>d<p>Decision to add cholinesterase inhibitors to Newfoundland and Labrador drug formulary announced by Liberal government on 18 September 2003 was delayed, after Liberal government defeated by Progressive Conservatives in October 2003 election.</p

Additional file 1: Figure S1. of Pharmacokinetics and safety of ixazomib plus lenalidomide–dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study

Waterfall plot of the best percent change in M-protein from baseline. Figure S2. Flowchart for ixazomib dose determination during cycle 1