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Neoadjuvant relatlimab and nivolumab in resectable melanoma
Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma
1
. We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg and relatlimab 160 mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate
2
. The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3–4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (
P
= 0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial
1
, provide further confirmation of the efficacy and safety of this new immunotherapy regimen.
Patients with resectable clinical stage III or oligometastatic stage IV melanoma were given neoadjuvant relatlimab and nivolumab combination immunotherapy, which induced a high pathologic complete response rate, indicating the efficacy and safety of this regimen.
Journal Article
Design, fabrication and control of soft robots
Conventionally, engineers have employed rigid materials to fabricate precise, predictable robotic systems, which are easily modelled as rigid members connected at discrete joints. Natural systems, however, often match or exceed the performance of robotic systems with deformable bodies. Cephalopods, for example, achieve amazing feats of manipulation and locomotion without a skeleton; even vertebrates such as humans achieve dynamic gaits by storing elastic energy in their compliant bones and soft tissues. Inspired by nature, engineers have begun to explore the design and control of soft-bodied robots composed of compliant materials. This Review discusses recent developments in the emerging field of soft robotics.
Journal Article
Leadership and religious schools : international perspectives and challenges
\"Leadership in religious schools is a complex and often misunderstood subject. Educational leaders must perform the dual task of encouraging religious identities while relating them to wider issues of citizenship. Religious identity needs to be made relevant to the whole school community--parents, staff, students--and leaders need to take care to expand how human identity is conceived and manifested. Given these challenges, learning and leadership take on a special importance in faith-based and religious schools. This unique volume brings together leading international scholars in the field to explore the many dimensions of leadership: religious, faith, spiritual, ministerial, educational, and curriculum leadership. The contributors demonstrate, through case studies and grounded theory, that these schools require leaders who are conversant with a very wide range of styles and issues. Other issues discussed include styles of leadership, relationships with stakeholders, motivation, satisfaction and stress, school culture, and ethos and charisma. This is an insightful collection of essays that will be of great use to all those studying and researching school leadership\"-- Provided by publisher.
Book
On the Practical Interpretability of Cross-Lagged Panel Models: Rethinking a Developmental Workhorse
Reciprocal feedback processes between experience and development are central to contemporary developmental theory. Autoregressive cross-lagged panel (ARCL) models represent a common analytic approach intended to test such dynamics. The authors demonstrate that—despite the ARCL model's intuitive appeal—it typically (a) fails to align with the theoretical processes that it is intended to test and (b) yields estimates that are difficult to interpret meaningfully. Specifically, using a Monte Carlo simulation and two empirical examples concerning the reciprocal relation between spanking and child aggression, it is shown that the cross-lagged estimates derived from the ARCL model reflect a weighted—and typically uninterpretable—amalgam of between- and within-person associations. The authors highlight one readily implemented respecification that better addresses these multiple levels of inference.
Journal Article
Microglia in Alzheimer’s disease
Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. Microglia express a wide range of receptors that act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition to their classical immune cell function, microglia act as guardians of the brain by promoting phagocytic clearance and providing trophic support to ensure tissue repair and maintain cerebral homeostasis. Conditions associated with loss of homeostasis or tissue changes induce several dynamic microglial processes, including changes of cellular morphology, surface phenotype, secretory mediators, and proliferative responses (referred to as an \"activated state\"). Activated microglia represent a common pathological feature of several neurodegenerative diseases, including Alzheimer's disease (AD). Cumulative evidence suggests that microglial inflammatory activity in AD is increased while microglial-mediated clearance mechanisms are compromised. Microglia are perpetually engaged in a mutual interaction with the surrounding environment in CNS; thus, diverse microglial reactions at different disease stages may open new avenues for therapeutic intervention and modification of inflammatory activities. In this Review, the role of microglia in the pathogenesis of AD and the modulation of microglia activity as a therapeutic modality will be discussed.
Journal Article
The Life-Giving Stone
InThe Life-Giving Stone, Michael Searcy provides a thought-provoking ethnoarchaeological account of metate and mano manufacture, marketing, and use among Guatemalan Maya for whom these stone implements are still essential equipment in everyday life and diet.Although many archaeologists have regarded these artifacts simply as common everyday tools and therefore unremarkable, Searcy's methodology reveals how, for the ancient Maya, the manufacture and use of grinding stones significantly impacted their physical and economic welfare. In tracing the life cycle of these tools from production to discard for the modern Maya, Searcy discovers rich customs and traditions that indicate how metates and manos have continued to sustain life-not just literally, in terms of food, but also in terms of culture. His research is based on two years of fieldwork among three Mayan groups, in which he documented behaviors associated with these tools during their procurement, production, acquisition, use, discard, and re-use.Searcy's investigation documents traditional practices that are rapidly being lost or dramatically modified. In few instances will it be possible in the future to observe metates and manos as central elements in household provisioning or follow their path from hand-manufacture to market distribution and to intergenerational transmission. In this careful inquiry into the cultural significance of a simple tool, Searcy's ethnographic observations are guided both by an interest in how grinding stone traditions have persisted and how they are changing today, and by the goal of enhancing the archaeological interpretation of these stones, which were so fundamental to pre-Hispanic agriculturalists with corn-based cuisines.
eBook