To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (investigational, extended-release of 5-fluorocytosine) into 5-fluorouracil. In preclinical models, 5-fluorouracil kills infected dividing cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activation against the tumor. In this dose ascending Ph1 trial (NCT01470794), Toca 511 was injected into the resection cavity wall of patients with rHGG, followed by courses of oral Toca FC. Additional cohorts included combination with bevacizumab or lomustine. Across the Ph1 program, the safety profile remains favorable. Objective responses (ORs) were assessed by IRR using MRI scans prior to Toca FC treatment as baseline. ORs occurred 6-19 months after Toca 511 administration, suggesting an immunologic mechanism. The ORs were observed in 4 patients with IDH1-wildtype and 2 patients with IDH1-mutant tumors, including 5 complete responses (CRs) with the investigational therapy alone, and 1 CR in combination with bevacizumab. The median duration of response (mDoR) was 35.1+ months. As of AUG2017, all responders were CR and remain alive. In a 23-patient subgroup who received high doses of Toca 511 and met Ph3 trial criteria, mOS was 14.4 months, 3-year survival rate was 26.1%, and mDoR was 35.7+ months with a durable response rate of 21.7%. Data suggest a positive association of durable response with OS.
Mild behavioral impairment (MBI) describes later life acquired, sustained neuropsychiatric symptoms (NPS) in cognitively normal individuals or those with mild cognitive impairment (MCI), as an at-risk state for incident cognitive decline and dementia. We developed an operational definition of MBI and tested whether the presence of MBI was related to caregiver burden in patients with subjective cognitive decline (SCD) or MCI assessed at a memory clinic.
MBI was assessed in 282 consecutive memory clinic patients with SCD (n = 119) or MCI (n = 163) in accordance with the International Society to Advance Alzheimer's Research and Treatment – Alzheimer's Association (ISTAART–AA) research diagnostic criteria. We operationalized a definition of MBI using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Caregiver burden was assessed using the Zarit caregiver burden scale. Generalized linear regression was used to model the effect of MBI domains on caregiver burden.
While MBI was more prevalent in MCI (85.3%) than in SCD (76.5%), this difference was not statistically significant (p = 0.06). Prevalence estimates across MBI domains were affective dysregulation (77.8%); impulse control (64.4%); decreased motivation (51.7%); social inappropriateness (27.8%); and abnormal perception or thought content (8.7%). Affective dysregulation (p = 0.03) and decreased motivation (p=0.01) were more prevalent in MCI than SCD patients. Caregiver burden was 3.35 times higher when MBI was present after controlling for age, education, sex, and MCI (p < 0.0001).
MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.
If all the world's a stage, as William Shakespeare suggested, only a few people have played their parts on a stage so grand as the White House, let alone cast themselves in the lead roles, written their own scripts, and directed their own performance. Yet this was the case with President John F. Kennedy and his wife, First Lady Jacqueline Kennedy, after they came to the White House in January 1961. Despite the barbs of latter-day critics, their nearly three-year run scored positive reviews at the time, set the benchmark against which subsequent performances would be measured, and still resonates in the popular imagination today. Indeed, it would become central to the approved story of the president's life, as later framed by his wife and family, and would be embedded forever in the many monuments to his memory, from his state funeral, to his gravesite at Arlington National Cemetery, to his presidential library and museum in Boston. When we remember John F. Kennedy, in other words, we are likely to remember the performer, as much as the person, and not only the part he played as president in his own White House productions but also the part his wife and others reproduced in the years following his death.
Comparing the Kennedys to stage performers or Hollywood stars is hardly a novel analogy, but the parallel has not been explored with an eye to its political content or to the way we remember the slain president. As they drafted the script for their productions, however, and as they directed the staging and played their parts, the Kennedys were also embellishing the office of the president, the authority of its occupant, and the prestige of the United States around the world. They were performing not just the presidency but the nation, defining not only the identities of the characters they played but that of the country as well. In these and other ways, their presentation of the presidency went beyond entertainment, or mere “style,” as some historians have described it. They created what marketers would call a “brand,” basically a positive representation of themselves and their country, and in the process, transformed performance into power, style into substance for an audience that seemed hungry for what their production had to say, not only about the president but also about themselves as Americans.
In his new book, Michael J. Hogan, a leading historian of the American presidency, offers a new perspective on John Fitzgerald Kennedy, as seen not from his life and times but from his afterlife in American memory. The Afterlife of John Fitzgerald Kennedy considers how Kennedy constructed a popular image of himself, in effect, a brand, as he played the part of president on the White House stage. The cultural trauma brought on by his assassination further burnished that image and began the process of transporting Kennedy from history to memory. Hogan shows how Jacqueline Kennedy, as the chief guardian of her husband's memory, devoted herself to embedding the image of the slain president in the collective memory of the nation, evident in the many physical and literary monuments dedicated to his memory. Regardless of critics, most Americans continue to see Kennedy as his wife wanted him remembered: the charming war hero, the loving husband and father, and the peacemaker and progressive leader who inspired confidence and hope in the American people.
Monuments of paper and pen were not the only vehicles of memory through which Jacqueline Kennedy and her family and friends would shape the image of John Fitzgerald Kennedy in the years following his death. There were other monuments as well, the most important being sites of memory where the president could be recalled in rituals of remembrance often approved by his widow. Through these sites, as through the many books she influenced, the former first lady would inscribe on the past her own vision of how the president should be remembered: as a man of strength and courage, a war hero and peacemaker, a daring explorer of new frontiers at home and in space, a champion of excellence in all venues, a man of faith and family, and a progressive reformer who had shed his blood – as Lincoln had before him – in service to his country and to all it represented. Her goal was to make John F. Kennedy a symbol of the nation, of what it meant to be an American, or at least of the ideals to which all Americans should aspire. With this goal in mind, she acted quickly to design her husband's memorial grave, launch a campaign to fund the Kennedy Presidential Library, and importune the new president to place his predecessor's name on both the National Culture Center in Washington, DC, and the space center in Cape Canaveral, Florida.
Much of this memorializing went on while the world remained in deep mourning for the president. It was expressed not only in state-sanctioned commemorations but also in private efforts to remember John Fitzgerald Kennedy, if only through the smallest gesture, the least expensive token. Such acts of commemoration, much like the president's funeral, further assuaged a nation still in the throes of an acute cultural trauma. They relieved the guilt and anxiety that many Americans felt, leaving in their place new symbols of national pride and confidence in the future. They also furthered the process by which the president was transformed into an American icon, very much the larger-than-life figure that Jacqueline Kennedy had in mind. His death would be framed in a narrative of national greatness; his identity linked to that of the nation itself; his life invested with meaning and purpose that would survive the grave.
The rededication of the Kennedy Presidential Library and Museum in 1993, one year before Jacqueline Kennedy's death, marked the culmination of her efforts to freeze in public memory the romantic image of her husband as the ideal American. The rededication followed a major renovation of the Columbia Point complex. Just as the Kennedys had once performed the presidency on the White House stage, the former first lady would now use the renovated museum, much like a theater, to reproduce her husband's life – not in all aspects, to be sure, but as she wanted others to see him. As before, the goal was to control the president's identity, define his legacy, and make him worthy of remembrance. With that goal in mind, a familiar narrative unfolded inside the museum, set amidst the usual props, precious artifacts, costumes, and symbols of the Kennedy presidency, but with little room left over for counternarratives or alternative memories. In its own way, the library half of the complex pursued the same goal. Family and friends still protected the president's memory, as they defined it, by limiting access to his records, favoring some scholars over others, and punishing those who would tarnish the sanctified image of the fallen hero. Not surprisingly, all of this led to yet another round of controversy between the library and the community of scholars who wanted to tell their own story of Kennedy's life and administration.
As this suggests, the library's purpose and that of the museum had not changed much, if at all, over the years. Nor, for that matter, had the ongoing debates, in both media commentary and historical scholarship, over how to define Kennedy and his place in American history. In the twenty years following the rededication of the Columbia Point complex, the old orthodoxy, once so aggressively championed by Jacqueline Kennedy, had only a little to add to what Schlesinger and Sorensen had said in the 1960s. Much the same was true of left-wing revisionism, which had its heyday in the 1970s and 1980s but faded thereafter. Some conservative critics, in their own version of revisionism, still denounced Kennedy as a weak and ineffective liberal while others made a tortuous effort to redefine the president as a virtuous conservative and precursor of Ronald Reagan.
The president woke up in a good mood on November 22, 1963. His back hurt more than usual, so he reinforced the corset he normally wore with a bandage-wrap for extra support. The discomfort did not darken his spirit, however; nor did the news of continued wrangling among leaders of the Democratic Party in Texas, particularly a squabble between conservative Governor John Connally and liberal Senator Ralph Yarborough that even Vice President Lyndon Johnson had been unable or unwilling to resolve. Despite this annoyance and his aching back, the president seemed more impressed by the large crowds and thunderous welcome that he and his wife had experienced during the first leg of their Texas trip. Even First Lady Jacqueline Kennedy, who normally disliked campaigning, was thrilled by their reception, and she and her husband had no reason to expect anything less from the day ahead. On the contrary, another enthusiastic crowd was already forming in the street below their hotel window. “I'll go anywhere with you,” said the first lady, as she watched a smile flash across the handsome face of her husband.
Nor was their mood darkened by a newspaper advertisement just published in the conservative Dallas Morning News. It began with sarcastic words welcoming President John F. Kennedy to the Lone Star State, but then launched a scurrilous attack, concealed in a series of leading questions, on the president's liberal policies at home and his supposedly soft stand on communism abroad. The ad revealed a degree of hostility toward the Kennedy administration that had been building for some time. Right-wing groups had physically and verbally assaulted Vice President Johnson and his wife when they campaigned in the state three years earlier, and similar groups had roughed up UN ambassador Adlai Stevenson during his visit to Dallas only a month before the president arrived. Stevenson was the darling of the liberal wing of the Democratic Party, a status that did not endear him to the increasingly conservative voters of Texas, who also viewed Johnson, a Texas native, as a traitor to his state for supporting the president's progressive agenda, especially on civil rights for African Americans.
All this was well known to Kennedy, as was the politics of the Dallas Morning News and its publisher and board chairman, E. M. Dealey.