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"Levitt, M"
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The weighty word book
Provides definitions for twenty-six vocabulary words from abasement to zealot with stories containing puns that provide mnemonic devices for remembering the definitions.
Book
Future of fundamental discovery in US biomedical research
Young researchers are crucially important for basic science as they make unexpected, fundamental discoveries. Since 1982, we find a steady drop in the number of grant-eligible basic-science faculty [principal investigators (PIs)] younger than 46. This fall occurred over a 32-y period when inflation-corrected congressional funds for NIH almost tripled. During this time, the PI success ratio (fraction of basicscience PIs who are R01 grantees) dropped for younger PIs (below 46) and increased for older PIs (above 55). This age-related bias seems to have caused the steady drop in the number of young basicscience PIs and could reduce future US discoveries in fundamental biomedical science. The NIH recognized this bias in its 2008 earlystage investigator (ESI) policy to fund young PIs at higher rates. We show this policy is working and recommend that it be enhanced by using better data. Together with the National Institute of General Medical Sciences (NIGMS) Maximizing Investigators’ Research Award (MIRA) program to reward senior PIs with research time in exchange for less funding, this may reverse a decades-long trend of more money going to older PIs. To prepare young scientists for increased demand, additional resources should be devoted to transitional postdoctoral fellowships already offered by NIH.
Journal Article
Weighty words, too
Provides definitions for twenty-six vocabulary words from \"aggrandizement\" to \"zany\" with stories containing puns that provide mnemonic devices for remembering the definitions.
Book
Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types
The immune response consists of a finely-tuned program, the activation of which must be coupled with inhibitory mechanisms whenever initiated. This ensures tight control of beneficial anti-pathogen and anti-tumor responses while preserving tissue integrity, promoting tissue repair, and safeguarding against autoimmunity. A cogent example of this binary response is in the mobilization of co-stimulatory and co-inhibitory signaling in regulating the strength and type of a T-cell response. Of particular importance is the costimulatory molecule CD28 which is countered by CTLA-4. While the role of CD28 in the immune response has been thoroughly elucidated, many aspects of CTLA-4 biology remain controversial. The expression of CD28 is largely constrained to constitutive expression in T-cells and as such, teasing out its function has been somewhat simplified by a limited and specific expression profile. The expression of CTLA-4, on the other hand, while reported predominantly in T-cells, has also been described on a diverse repertoire of cells within both lymphoid and myeloid lineages as well as on the surface of tumors. Nonetheless, the function of CTLA-4 has been mostly described within the context of T-cell biology. The focus on T-cell biology may be a direct result of the high degree of amino acid sequence homology and the co-expression pattern of CD28 and CTLA-4, which initially led to the discovery of CTLA-4 as a counter receptor to CD28 (for which a T-cell-activating role had already been described). Furthermore, observations of the outsized role of CTLA-4 in T reg -mediated immune suppression and the striking phenotype of T-cell hyperproliferation and resultant disease in CTLA-4 −/− mice contribute to an appropriate T-cell-centric focus in the study of CTLA-4. Complete elucidation of CTLA-4 biology, however, may require a more nuanced understanding of its role in a context other than that of T-cells. This makes particular sense in light of the remarkable, yet limited utility of anti-CTLA-4 antibodies in the treatment of cancers and of CTLA-4-Ig in autoimmune disorders like rheumatoid arthritis. By fully deducing the biology of CTLA-4-regulated immune homeostasis, bottlenecks that hinder the widespread applicability of CTLA-4-based immunotherapies can be resolved.
Journal Article
CD8+CD161+ T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential
NK1.1 and its human homolog CD161 are expressed on NK cells, subsets of CD4 + and CD8 + T cells, and NKT cells. While the expression of NK1.1 is thought to be inhibitory to NK cell function, it is reported to play both costimulatory and coinhibitory roles in T-cells. CD161 has been extensively studied and characterized on subsets of T-cells that are MR1-restricted, IL-17 producing CD4 + (T H 17 MAIT cells) and CD8 + T cells (Tc17 cells). Non-MAIT, MR1-independent CD161-expressing T-cells also exist and are characterized as generally effector memory cells with a stem cell like phenotype. Gene expression analysis of this enigmatic subset indicates a significant enhancement in the expression of cytotoxic granzyme molecules and innate like stress receptors in CD8 + NK1.1 + /CD8 + CD161 + cells in comparison to CD8 + cells that do not express NK1.1 or CD161. First identified and studied in the context of viral infection, the role of CD8 + CD161 + T-cells, especially in the context of tumor immunology, is still poorly understood. In this review, the functional characteristics of the CD161-expressing CD8 + T cell subset with respect to gene expression profile, cytotoxicity, and tissue homing properties are discussed, and application of this subset to immune responses against infectious disease and cancer is considered.
Journal Article
Does the perceived quality of interdisciplinary research vary between fields?
PurposeTo assess whether interdisciplinary research evaluation scores vary between fields.Design/methodology/approachThe authors investigate whether published refereed journal articles were scored differently by expert assessors (two per output, agreeing a score and norm referencing) from multiple subject-based Units of Assessment (UoAs) in the REF2021 UK national research assessment exercise. The primary raw data was 8,015 journal articles published 2014–2020 and evaluated by multiple UoAs, and the agreement rates were compared to the estimated agreement rates for articles multiply-evaluated within a single UoA.FindingsThe authors estimated a 53% agreement rate on a four-point quality scale between UoAs for the same article and a within-UoA agreement rate of 70%. This suggests that quality scores vary more between fields than within fields for interdisciplinary research. There were also some hierarchies between fields, in the sense of UoAs that tended to give higher scores for the same article than others.Research limitations/implicationsThe results apply to one country and type of research evaluation. The agreement rate percentage estimates are both based on untested assumptions about the extent of cross-checking scores for the same articles in the REF, so the inferences about the agreement rates are tenuous.Practical implicationsThe results underline the importance of choosing relevant fields for any type of research evaluation.Originality/valueThis is the first evaluation of the extent to which a careful peer-review exercise generates different scores for the same articles between disciplines.
Journal Article
Guidelines for the management of postoperative soiling in children with Hirschsprung disease
Although most children with Hirschsprung disease ultimately achieve functional and comfortable stooling, some will experience a variety of problems after pull-through surgery. The most common problems include soiling, obstructive symptoms, enterocolitis, and failure to thrive. The purpose of this guideline is to present a rational approach to the management of postoperative soiling in children with Hirschsprung disease. The American Pediatric Surgical Association Hirschsprung Disease Interest Group engaged in a literature review and group discussions. Expert consensus was then used to summarize the current state of knowledge regarding causes, methods of diagnosis, and treatment approaches to children with soiling symptoms following pull-through for Hirschsprung disease. Causes of soiling after pull-through are broadly categorized as abnormalities in sensation, abnormalities in sphincter control, and “pseudo-incontinence.” A stepwise algorithm for the diagnosis and management of soiling after a pull-through for Hirschsprung disease is presented; it is our hope that this rational approach will facilitate treatment and optimize outcomes.
Journal Article
The wearable activity technology and action-planning trial in cancer survivors: Physical activity maintenance post-intervention
The study objective was to assess whether moderate-to-vigorous intensity physical activity (MVPA) change in cancer survivors (n = 68, mean age = 64 years) was maintained 12-weeks following the Wearable Activity Technology and Action Planning (WATAAP) intervention. Secondary aims were to assess the effects of the intervention on blood pressure (BP) and body mass index (BMI), and to explore group differences between baseline and 24-weeks.
Randomized controlled trial.
MVPA and sedentary behaviour were assessed using an accelerometer at baseline, the end of the intervention (12-weeks), and at 24-weeks. Generalised linear mixed models with random effects were used to examine between-group and within-group changes in MVPA, sedentary behaviour, BP and BMI.
MVPA was significantly higher in the intervention group compared with the control group at 24-weeks following adjustment for known confounders (141.4 min/wk. (95% CI = 9.1 to 273.8), p = 0.036). At 24-weeks participants in the intervention group had maintained their increased levels of MVPA (change from 12-weeks = 8.8 min/wk.; 95% CI = −43 to 61; p = 0.74). The reduction in MVPA in the control group over the first 12-weeks was also maintained at 24-weeks (5.4 min/wk.; 95% CI = −3.6 to 4.6; p = 0.80). Secondary outcomes did not differ between groups at 24-weeks.
Our results suggest distance-based interventions using wearable technology produce increases in MVPA that endure at least 12-weeks after the intervention is completed.
Journal Article