Multicontrast connectometry: A new tool to assess cerebellum alterations in early relapsing-remitting multiple sclerosis.

BACKGROUND: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. METHODS: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. RESULTS: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. CONCLUSION: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage. Hum Brain Mapp 36:1609-1619, 2015. © 2014 Wiley Periodicals, Inc.

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

The Bee

Newspaper reporting on contemporary events of the wars in North America and Europe including the Battle of Queenston Heights and the death of Isaac Brock. News items include: Page 1: Sheaffe announcement regulating the sale of alcohol in Niagara; Myers announcement asking citizens for the return of American muskets recovered from the battle at Queenston; local notices on business claims and education; want ads for wood, straw, flour and pork for military use; announcement by the Prince Regent in Council putting an embargo on American ships. Page 2: release of American prisoners captured at Queenston; results of a battle by Riga, Latvia the French army under MacDonald against Russia; address of Emperor Alexander I of Russia to troops on declaring war on France; news of the British Navy; mediation between Spain and South American colonies; the security of Canadian properties in wartime; American ships leaving Britain with licenses. Page 3: American ships leaving Britain with licenses; Russian General Platoff’s (Platov) victory over Polish Uhlans; Battle of Salamanca with Lord Wellington. Page 4: report on the Battle of Queenston Heights and the death of Isaac Brock.

City of St. Catharines fonds, 1951-1964, 1970-1973, 1978-1982, n.d.

The fonds contains materials relating to the City of St. Catharines from the 1950s to 1980s. The materials included are correspondence, clippings, media releases, and some photographs. Folders are arranged alphabetically and then chronologically within each series. The series are arranged alphabetically.

The Gentleman's Magazine and Historical Chronicle - 1812 July

Specific pages with War of 1812 content in this volume: Page 77: The American senate declares war on Great Britain. Click on the pdf links to the right to view the monthly issue. The Gentleman's Magazine and Historical Chronicle was a monthly periodical published in England during the years of 1736-1833. The volumes of interest from 1812-1815 were written and compiled by Sylvanus Urban, Gentleman. These volumes were printed in London by Nichols, Son and Bentley at Cicero's Head, Red Lion Passage and Fleet Street. The magazine contains accounts of important historical events, abstracts of foreign occurrences, letters from noted figures, articles on geography, biographical entries for prominent people, poems, statistics, obituaries, reviews of books and more.

The Gentleman's Magazine and Historical Chronicle - 1812 August

Specific pages with War of 1812 content in this volume: August: Page 179: The official American declaration of war. Click on the pdf links to the right to view the monthly issue. The Gentleman's Magazine and Historical Chronicle was a monthly periodical published in England during the years of 1736-1833. The volumes of interest from 1812-1815 were written and compiled by Sylvanus Urban, Gentleman. These volumes were printed in London by Nichols, Son and Bentley at Cicero's Head, Red Lion Passage and Fleet Street. The magazine contains accounts of important historical events, abstracts of foreign occurrences, letters from noted figures, articles on geography, biographical entries for prominent people, poems, statistics, obituaries, reviews of books and more.

The Weekly Register September 1811 to March 1812

The Weekly Register, also known as Niles Weekly Register was a weekly periodical edited by Hezekiah Niles (1777-1839), and published in Baltimore Maryland. Volumes of Interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century Politics and Government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Pages are divided as follows: 1811 September 7th pages 1-16 14th pages 17-32 21st pages 33-48 28th pages 49-72 1811 October 5th pages 73-88 12th pages 89-104 19th pages 105-120 26th pages 121-136 1811 November 2nd pages 137-152 9th pages 153-184 15th pages 185-208 23rd pages 209-224 30th pages 225-240 1811 December 7th pages 241-256 14th pages 257-280 21st pages 281-296 28th pages 299-320 1812 January 4th pages 321-336 11th pages 337-360 18th pages 361-376 25th pages 377-392 1812 February 1st pages 393-408 8th pages 409-432 15th pages 433-448 22nd pages 449-464 29th pages 465-480 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Call Number: SPCL PER JK 1 N52

The Weekly Register - March 1813 and Index

Issues for the March 1813 Weekly Register newspaper (Baltimore, Maryland) are divided and includes the following War of 1812 related stories: March 6th, pages 1-16: Editor's proclamation on reporting on the war (p.1); Declaration of British Parliament - 9 January 1813 (pp.1-6); President's message to Senate and House of Representatives - February 24 (p.8); Events of the War including reports from Ogdensburgh,Battle of Frenchtown with Brigadier General James Winchester, Colonel Henry Proctor, and Round Head; (pp.9-13); naval events (pp.13-15); President Madison's speech - March 4 (pp.15-16). March 13th, pages 17-40 March 20th, pages 41-56 March 27th, pages 57-72 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52

The Weekly Register - September 1811 and Index

Issues for the September 1811 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: September 7th, pages 1-16 September 14th, pages 17-32 September 21st, pages 33-48 September 28th, pages 49-72 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52

The Weekly Register - November 1811

Issues for the November 1811 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: November 2nd, pages 137-152 November 9th, pages 153-184 November 15th, pages 185-208 November 23rd, pages 209-224 November 30th, pages 225-240 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest.Call Number: SPCL PER JK 1 N52

The Weekly Register - October 1811

Issues for the October 1811 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: October 5th, pages 73-88 October 12th, pages 89-104 October 19th, pages 105-120 October 26th, pages 121-136 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52

The Weekly Register - December 1811

Issues for the December 1811 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: December 7th, pages 241-256 December 14th, pages 257-280 December 21st, pages 281-296 December 28th, pages 299-320 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52

The Weekly Register - January 1812

Pages for the month of January 1812 are divided as follows: January 4th, pages 321-336 January 11th, pages 337-360 January 18th, pages 361-376 January 25th, pages 377-392 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest.Call Number: SPCL PER JK 1 N52

The Weekly Register - February 1812

Issues for the February 1812 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: February 1st, pages 393-408 February 8th, pages 409-432 February 15th, pages 433-448 February 22nd, pages 449-464 February 29th, pages 465-480 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52

The Weekly Register - April 1813

Issues for the April 1813 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: April 3rd, pages 73-88 April 10th, pages 89-104 April 17th, pages 105-120 April 24th, pages 121-136 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest.Call Number: SPCL PER JK 1 N52