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"Craig, Brian"
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Batman noir : Gotham by gaslight
\"Now presented in ... black-and-white pencils and inks, it's Batman vs. Jack the Ripper in Victorian-era London ... [in which] Bruce Wayne is operating as the bat-garbed vigilante, the Batman, who is feared by the guilty and the innocent alike\"-- Provided by publisher.
Book
Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma
Neuroblastoma (NBL) cells highly express disialoganglioside GD2, which is restricted and weakly expressed in selected healthy cells, making it a desirable target of immunotherapy. Over the past two decades, application of dinutuximab, an anti-GD2 monoclonal antibody (mAb), has been one of the few new therapies to substantially improve outcomes to current levels. Given the persistent challenge of relapse and therapeutic resistance, there is an urgent need for new effective and tolerable treatment options for high-risk NBL. Recent breakthroughs in immune checkpoint inhibitor (ICI) therapeutics have not translated into high-risk NBL, like many other major pediatric solid tumors. Given the suppressed tumor microenvironment (TME), single ICIs like anti-CTLA4 and anti-PD1 have not demonstrated significant antitumor response rates. Meanwhile, emerging studies are reporting novel advancements in GD2-based therapies, targeted therapies, nanomedicines, and other immunotherapies such as adoptive transfer of natural killer (NK) cells and chimeric antigen receptors (CARs), and these hold interesting promise for the future of high-risk NBL patient care. Herein, we summarize the current state of the art in NBL therapeutic options and highlight the unique challenges posed by NBL that have limited the successful adoption of immune-modifying therapies. Through this review, we aim to direct the field’s attention to opportunities that may benefit from a combination immunotherapy strategy.
Journal Article
Runaways omnibus
They were six normal teenagers linked only by their wealthy parents' annual business meeting ... until a chance discovery revealed the shocking truth: their parents are the secret criminal society known as the Pride. For years, the Pride controlled all criminal activity in Los Angeles, ruling the city with an iron fist ... and now, with their true natures exposed, the Pride will take any measures necessary to protect their organization--even if it means taking out their own children. Now on the run from their villainous parents, Nico, Chase, Karolina, Gertrude, Molly and Alex have only each other to rely on.
Book
Targeted immune activation in pediatric solid tumors: opportunities to complement local control approaches
Surgery or radiation therapy is nearly universally applied for pediatric solid tumors. In many cases, in diverse tumor types, distant metastatic disease is present and evades surgery or radiation. The systemic host response to these local control modalities may lead to a suppression of antitumor immunity, with potential negative impact on the clinical outcomes for patients in this scenario. Emerging evidence suggests that the perioperative immune responses to surgery or radiation can be modulated therapeutically to preserve anti-tumor immunity, with the added benefit of preventing these local control approaches from serving as pro-tumorigenic stimuli. To realize the potential benefit of therapeutic modulation of the systemic response to surgery or radiation on distant disease that evades these modalities, a detailed knowledge of the tumor-specific immunology as well as the immune responses to surgery and radiation is imperative. In this Review we highlight the current understanding of the tumor immune microenvironment for the most common peripheral pediatric solid tumors, the immune responses to surgery and radiation, and current evidence that supports the potential use of immune activating agents in the perioperative window. Finally, we define existing knowledge gaps that limit the current translational potential of modulating perioperative immunity to achieve effective anti-tumor outcomes.
Journal Article
The Flash : starting line
\"Struck by a bolt of lightning and doused in chemicals, police scientist Barry Allen was transformed into the Fastest Man Alive and Central City's hero. With stunning art and a brand new cover illustration by Francis Manapul, The Flash: Starting Line is the definitive Scarlet Speedster adventure for and an excellent jumping on point. Saving the world has earned the Flash some powerful enemies--in fact, a gallery of them. Captain Cold, Heat Wave, Mirror Master, Glider, the Trickster and Weather Wizard, a group of super-villains known as the Rogues, live their lives to pillage and steal from Central City... with only one man standing in their way.\"-- Provided by publisher.
Book
Risk factors for congenital heart disease: The Baby Hearts Study, a population-based case-control study
We investigated the role of maternal environmental factors in the aetiology of congenital heart disease (CHD). A population-based case-control study (242 CHD cases, 966 controls) was conducted using an iPad questionnaire for mother with linkage to maternity and first trimester prescription records. Risk of CHD was associated with low maternal education (OR adjusted for confounders 1.59; 95% confidence interval [CI], 1.02-2.49), pregestational diabetes (OR 4.04; 95% CI 1.00-16.28), self-reported maternal clotting disorders (adjOR 8.55, 95%CI 1.51-48.44), prescriptions for the anticlotting medication enoxaparin (adjOR 3.22, 95%CI 1.01-10.22) and self-reported vaginal infections (adjOR 1.69, 95%CI 1.01-2.80). There was no strong support for the hypothesis that periconceptional folic acid supplements have a protective effect, but there was a protective effect of frequent consumption of folate rich fruits (adjOR 0.64, 95%CI 0.47-0.89). Compared to the most common pre-pregnancy dietary pattern, CHD risk was associated with a poor diet low in fruit and vegetables (adjOR 1.56, 95%CI 1.05-2.34). Mothers of cases reported more pregnancy related stress (adjOR 1.69; 95% CI 1.22-2.34) and multiple stressors (adjOR 1.94, 95%CI 0.83-4.53). We found no supportive evidence for CHD risk being associated with obesity, smoking, depression or antidepressant use in this population. Our findings add to the previous evidence base to show potential for public health approaches to help prevent CHD in future by modifying environmental factors. Independent confirmation should be sought regarding elevated CHD risk associated with maternal blood clotting disorders and their treatment, since we are the first to report this.
Journal Article
Perioperative poly(I:C) reverses accelerated tumor growth after surgery in neuroblastoma
Abstract
Surgery for local control is a cornerstone of anticancer therapy with demonstrated survival benefit. However, surgery-induced modulation of antitumor immunity may also contribute to cancer progression and relapse. Despite evidence for a pro-tumor surgery effect in adult cancers, there remain significant knowledge gaps as to the influence surgery has on recurrence or metastatic outgrowth in pediatric cancers. High-risk neuroblastoma (HR-NB) is the most common extracranial solid tumor of childhood. While almost all children with HR-NB undergo surgery, nearly 50% suffer metastatic relapse and succumb to their disease. To ascertain if surgery may contribute to recurrence in HR-NB, we developed a mouse model to comprehensively interrogate the systemic effect of surgery on distant tumor growth and immune modulation. This model demonstrated that MYCN-amplified HR-NB tumor growth was accelerated by surgery compared to tumor-bearing mice without surgical stress. Accelerated tumor growth was absent in HR-NB cells engrafted to immune deficient mice, suggesting that an intact immune system may be needed for surgery to exert its pro-growth effect on distant tumor cells. Consistent with that genetic ablation model, flow cytometry measured a decrease in splenic macrophages (Mϕ) and dendritic cells (DC) and an increase in myeloid-derived suppressor cells (MDSC) after surgery. Perioperative treatment with polyinosinic-polycytidylic acid [poly(I:C)] ameliorated surgery-induced tumor growth. These findings provide direct insight into the systemic surgical effect on pediatric solid tumor growth and identify innate immune adjuvants as a potential perioperative treatment to mitigate this effect.
Journal Article
The Flash
\"When Wally West, the adolescent nephew of the Flash's fiancee accidentally gained powers of superspeed, he became the Scarlet Speedster's sidekick. Growing up as his hero's protege, Kid Flash had a childhood of amazing action and adventure. But on the day that The Flash died, Wally's carefree adolescence abruptly ended and his life as an adult began. THE FLASH BY MARK WAID BOOK ONE looks back at Wally's earliest days as the Kid Flash and explores the gamut of his emotions and experiences from his first day as a child hero to his succession of Barry Allen as the new Flash. A journey full of humor and drama, this story shows just how much Wally West loves being the fastest man alive\"-- Provided by publisher.
Book
Exercise prescription improves exercise tolerance in young children with CHD: a randomised clinical trial
ObjectiveThe main objective of this study was to ascertain if a structured intervention programme can improve the biophysical health of young children with congenital heart disease (CHD). The primary end point was an increase in measureable physical activity levels following the intervention.MethodsPatients aged 5–10 years with CHD were identified and invited to participate. Participants completed a baseline biophysical assessment, including a formal exercise stress test and daily activity monitoring using an accelerometer. Following randomisation, the intervention group attended a 1 day education session and received an individual written exercise plan to be continued over the 4-month intervention period. The control group continued with their usual level of care. After 4 months, all participants were reassessed in the same manner as at baseline.ResultsOne hundred and sixty-three participants (mean age 8.4 years) were recruited, 100 of whom were male (61.3%). At baseline, the majority of the children were active with good exercise tolerance. The cyanotic palliated subgroup participants, however, were found to have lower levels of daily activity and significantly limited peak exercise performance compared with the other subgroups. One hundred and fifty-two participants (93.2%) attended for reassessment. Following the intervention, there was a significant improvement in peak exercise capacity in the intervention group. There was also a trend towards increased daily activity levels.ConclusionOverall physical activity levels are well preserved in the majority of young children with CHD. A structured intervention programme significantly increased peak exercise capacity and improved attitudes towards positive lifestyle changes.
Journal Article