Fund Black scientists Stevens, Kelly R.; Masters, Kristyn S.; Imoukhuede, P.I. ...
Cell,
02/2021, Letnik:
184, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty ...in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.
Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.
Background
99m
TcTilmanocept, a novel CD206 receptor-targeted radiopharmaceutical, was evaluated in an open-label, phase III trial to determine the false negative rate (FNR) of sentinel lymph node ...biopsy (SLNB) relative to the pathologic nodal status in patients with intraoral or cutaneous head and neck squamous cell carcinoma (HNSCC) undergoing tumor resection, SLNB, and planned elective neck dissection (END). Negative predictive value (NPV), overall accuracy of SLNB, and the impact of radiopharmaceutical injection timing relative to surgery were assessed.
Methods and Findings
This multicenter, non-randomized, single-arm trial (ClinicalTrials.gov identifier NCT00911326) enrolled 101 patients with T1–T4, N0, and M0 HNSCC. Patients received 50 µg
99m
Tctilmanocept radiolabeled with either 0.5 mCi (same day) or 2.0 mCi (next day), followed by lymphoscintigraphy, SLNB, and END. All excised tissues were evaluated for tissue type and tumor presence.
99m
TcTilmanocept identified one or more SLNs in 81 of 83 patients (97.6 %). Of 39 patients identified with any tumor-positive nodes (SLN or non-SLN), one patient had a single tumor-positive non-SLN in whom all SLNs were tumor-negative, yielding an FNR of 2.56 %; NPV was 97.8 % and overall accuracy was 98.8 %. No significant differences were observed between same-day and next-day procedures.
Conclusions
Use of receptor-targeted
99m
Tctilmanocept for lymphatic mapping allows for a high rate of SLN identification in patients with intraoral and cutaneous HNSCC. SLNB employing
99m
Tctilmanocept accurately predicts the pathologic nodal status of intraoral HNSCC patients with low FNR, high NPV, and high overall accuracy. The use of
99m
Tctilmanocept for SLNB in select patients may be appropriate and may obviate the need to perform more extensive procedures such as END.
Sentinel lymph node (SLN) mapping is common, however question remains as to what the ideal imaging agent is and how such an agent might provide reliable and stable localization of SLNs.
99m
...Tc-labeled nanocolloid human serum albumin (Nanocoll
®
) is the most commonly used radio-labeled colloid in Europe and remains the standard of care (SOC). It is used in conjunction with vital blue dyes (VBDs) which relies on simple lymphatic drainage for localization. Although the exact mechanism of Nanocoll SLN localization is unknown, there is general agreement that Nanocoll exhibits the optimal size distribution and radiolabeling properties of the commercially available radiolabel colloids.
99m
TcTilmanocept is a novel radiopharmaceutical designed to address these deficiencies. Our aim was to compare
99m
TcTilmanocept to Nanocoll for SLN mapping in breast cancer. Data from the Phase III clinical trials of
99m
TcTilmanocept’s concordance with VBD was compared to a meta-analysis of a review of the literature to identify a
99m
Tc albumin colloid SOC. The primary endpoints were SLN localization rate and degree of localization. Six studies were used for a meta-analysis to identify the colloid-based SOC. Five studies (6,134 patients) were used to calculate the SOC localization rate of 95.91 % (CI 0.9428–0.9754) and three studies (1,380 patients) were used for the SOC SLN degree of localization of 1.6683 (CI 1.5136–1.8230). The lower bound of the confidence interval was used for comparison to Tilmanocept. Tilmanocept data included 148 patients, and pooled analysis revealed a 99.99 % (CI 0.9977–1.0000) localization rate and degree of localization of 2.16 (CI 1.964–2.3600). Tilmanocept was superior to the Nanocoll SOC for both endpoints (
P
< 0.0001).
Issue Title: Biomarkers of Cancer Metastasis Through the Lymphvascular System Sentinel lymph node (SLN) mapping is common, however question remains as to what the ideal imaging agent is and how such ...an agent might provide reliable and stable localization of SLNs. ^sup 99m^Tc-labeled nanocolloid human serum albumin (Nanocoll^sup ^) is the most commonly used radio-labeled colloid in Europe and remains the standard of care (SOC). It is used in conjunction with vital blue dyes (VBDs) which relies on simple lymphatic drainage for localization. Although the exact mechanism of Nanocoll SLN localization is unknown, there is general agreement that Nanocoll exhibits the optimal size distribution and radiolabeling properties of the commercially available radiolabel colloids. ^sup 99m^TcTilmanocept is a novel radiopharmaceutical designed to address these deficiencies. Our aim was to compare ^sup 99m^TcTilmanocept to Nanocoll for SLN mapping in breast cancer. Data from the Phase III clinical trials of ^sup 99m^TcTilmanocept's concordance with VBD was compared to a meta-analysis of a review of the literature to identify a ^sup 99m^Tc albumin colloid SOC. The primary endpoints were SLN localization rate and degree of localization. Six studies were used for a meta-analysis to identify the colloid-based SOC. Five studies (6,134 patients) were used to calculate the SOC localization rate of 95.91 % (CI 0.9428-0.9754) and three studies (1,380 patients) were used for the SOC SLN degree of localization of 1.6683 (CI 1.5136-1.8230). The lower bound of the confidence interval was used for comparison to Tilmanocept. Tilmanocept data included 148 patients, and pooled analysis revealed a 99.99 % (CI 0.9977-1.0000) localization rate and degree of localization of 2.16 (CI 1.964-2.3600). Tilmanocept was superior to the Nanocoll SOC for both endpoints (P < 0.0001).PUBLICATION ABSTRACT
Bumble bees are integral pollinators of native and cultivated plant communities, but species are undergoing significant changes in range and abundance on a global scale. Climate change and land cover ...alteration are key drivers in pollinator declines; however, limited research has evaluated the cumulative effects of these factors on bumble bee assemblages. This study tests bumble bee assemblage (calculated as richness and abundance) responses to climate and land use by modeling species‐specific habitat requirements, and assemblage‐level responses across geographic regions. We integrated species richness, abundance, and distribution data for 18 bumble bee species with site‐specific bioclimatic, landscape composition, and landscape configuration data to evaluate the effects of multiple environmental stressors on bumble bee assemblages throughout 433 agricultural fields in Florida, Indiana, Kansas, Kentucky, Maryland, South Carolina, Utah, Virginia, and West Virginia from 2018 to 2020. Distinct east versus west groupings emerged when evaluating species‐specific habitat associations, prompting a detailed evaluation of bumble bee assemblages by geographic region. Maximum temperature of warmest month and precipitation of driest month had a positive impact on bumble bee assemblages in the Corn Belt/Appalachian/northeast, southeast, and northern plains regions, but a negative impact on the mountain region. Further, forest land cover surrounding agricultural fields was highlighted as supporting more rich and abundant bumble bee assemblages. Overall, climate and land use combine to drive bumble bee assemblages, but how those processes operate is idiosyncratic and spatially contingent across regions. From these findings, we suggested regionally specific management practices to best support rich and abundant bumble bee assemblages in agroecosystems. Results from this study contribute to a better understanding of climate and landscape factors affecting bumble bees and their habitats throughout the United States.
Bumble bee communities are changing due to climate change and land cover alteration. This study integrated richness, abundance, and distribution data for 18 bumble bee species with site‐specific climate, landscape composition, and landscape configuration data to evaluate the effects of environmental stressors on bumble bees throughout 433 agricultural fields in the United States. Temperature, precipitation, and surrounding landscape influenced bumble bee species, but these effects differed by geographic region, notably between the east and west. These results enhance our understanding of bumble bee habitat needs and suggest region‐specific management practices to support rich and diverse bumble bee populations in agroecosystems.
Pollinators play pivotal roles in maintaining agricultural and natural plant communities, yet some bee populations are declining. Loss of pollinator habitats as a result of agricultural ...intensification and urbanization have reduced bee abundance and diversity. Additionally, climate change has affected bee distributions and led to disruption of plant-pollinator synchrony, impacting ecosystem processes. However, how these factors concurrently influence bee assemblages is poorly understood. Therefore, we evaluated bumble bee (Bombus) assemblages in relation to the proportion of agricultural, semi-natural, and urban land cover and interannual variation in temperature, precipitation, and relative humidity in Utah agroecosystems using Bombus captured as bycatch in pest monitoring traps from 2014 to 2018. Bombus assemblage composition was highest in agricultural sites with increased agricultural land cover in the surrounding area, low temperatures, and high relative humidity during the growing season; and lowest in sites with increased urban land cover, high temperatures, and low relative humidity. Functional dispersion did not differ among these groups indicating a range of tongue lengths, body sizes, hair lengths, and hair types were present within all agricultural sites. Further, high beta-diversity, as indicated by unique Bombus assemblages among sites, suggests that all agricultural sites in this study have potential conservation value for maintaining Bombus communities. Therefore, it is important that diverse habitats for pollinators are maintained through targeted management techniques. Additionally, our collection of Bombus from mid-May to mid-September identified phenological overlap within Bombus assemblages, which helps ensure pollination services are provided even if a particular species is lost due to environmental disturbances. However, while there is overlap in functional traits and phenology, considerations should be given due to widespread pollinator declines. Overall, evaluating landscape and climate variables together may yield more realistic results and better inform effective management and land-use planning strategies to prevent ecological homogenization and to foster future resiliency of Bombus populations.
•The combined effects of land cover and climate impact Bombus in agroecosystems.•Bombus composition was highest with crop land, low temperatures and high humidity.•Bombus composition was lowest with urban land, high temperatures and low humidity.•Phenological overlap among species provides functional redundancy.•High Bombus turnover suggests all surveyed sites have conservation value.
Abstract
Commercialized bumble bees (Bombus) are primary pollinators of several crops within open field and greenhouse settings. However, the common eastern bumble bee (Bombus impatiens Cresson, ...1863) is the only species widely available for purchase in North America. As an eastern species, concerns have been expressed over their transportation outside of their native range. Therefore, there is a need to identify regionally appropriate candidates for commercial crop pollination services, especially in the western U.S.A. In this study, we evaluated the commercialization potential of brown-belted bumble bees (Bombus griseocollis De Geer, 1773), a broadly distributed species throughout the U.S.A., by assessing nest initiation and establishment rates of colonies produced from wild-caught gynes, creating a timeline of colony development, and identifying lab-reared workers’ critical thermal maxima (CTMax) and lethal temperature (ecological death). From 2019 to 2021, 70.6% of the wild-caught B. griseocollis gynes produced brood in a laboratory setting. Of these successfully initiated nests, 74.8% successfully established a nest (produced a worker), providing guidance for future rearing efforts. Additionally, lab-reared workers produced from wild-caught B. griseocollis gynes had an average CTMax of 43.5°C and an average lethal temperature of 46.4°C, suggesting B. griseocollis can withstand temperatures well above those commonly found in open field and greenhouse settings. Overall, B. griseocollis should continue to be evaluated for commercial purposes throughout the U.S.A.
Since the early 1990s, morbidity and mortality in tortoise populations have been associated with a transmissible, mycoplasmal upper respiratory tract disease (URTD). Although the etiology, ...transmission, and diagnosis of URTD have been extensively studied, little is known about the dynamics of disease transmission in free-ranging tortoise populations
.
To understand the transmission dynamics of
Mycoplasma agassizii
, the primary etiological agent of URTD in wild tortoise populations, we studied 11 populations of free-ranging gopher tortoises (
Gopherus polyphemus
;
n
= 1667 individuals) over five years and determined their exposure to the pathogen by serology, by clinical signs, and by detection of the pathogen in nasal lavages. Adults tortoises (
n
= 759) were 11 times more likely to be seropositive than immature animals (
n
= 242) (odds ratio = 10.6, 95% CI = 5.7-20,
P
< 0.0001). Nasal discharge was observed in only 1.4% (4/296) of immature tortoises as compared with 8.6% (120/1399) of adult tortoises. Nasal lavages from all juvenile tortoises (
n
= 283) were negative by PCR for mycoplasmal pathogens associated with URTD. We tested for spatial segregation among tortoise burrows by size class and found no consistent evidence of clustering of either juveniles or adults. We suggest that the social behavior of tortoises plays a critical role in the spread of URTD in wild populations, with immature tortoises having minimal interactions with adult tortoises, thereby limiting their exposure to the pathogen. These findings may have broader implications for modeling horizontally transmitted diseases in other species with limited parental care and emphasize the importance of incorporating animal behavior parameters into disease transmission studies to better characterize the host-pathogen dynamics.
Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. ...Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 - 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased cortical alpha center frequency and alpha oscillatory synchronization. Full resolution of PTSD symptoms was attained in over 50% of patients. These data support DMN involvement in PTSD pathophysiology and suggest a role in therapeutic outcomes. Prospective, sham controlled PrTMS® trials may be warranted to validate our clinical findings and to examine the contribution of DMN targeting for novel preventive, diagnostic, and therapeutic strategies tailored to the unique needs of individual patients with both combat and non-combat PTSD.
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