Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
58,335
result(s) for
"Alexander, M"
Sort by:
Cutaneous melanoma
In the past decade, major advances have been made in the understanding of melanoma. New predisposition genes have been reported and key somatic events, such as BRAF mutation, directly translated into therapeutic management. Surgery for localised melanoma and regional lymph node metastases is the standard of care. Sentinel-node biopsy provides precise staging, but has not been reported to affect survival. The effect of lymph-node dissection on survival is a topic of investigation. Two distinct approaches have emerged to try to extend survival in patients with metastatic melanoma: immunomodulation with anti-CTLA4 monoclonal antibodies, and targeted therapy with BRAF inhibitors or MEK inhibitors for BRAF-mutated melanoma. The combination of BRAF inhibitors and MEK inhibitors might improve progression-free survival further and, possibly, increase overall survival. Response patterns differ substantially—anti-CTLA4 immunotherapy can induce long-term responses, but only in a few patients, whereas targeted drugs induce responses in most patients, but nearly all of them relapse because of pre-existing or acquired resistance. Thus, the long-term prognosis of metastatic melanoma remains poor. Anti-PD1 and anti-PDL1 antibodies have emerged as breakthrough drugs for melanoma that have high response rates and long durability. Biomarkers that have predictive value remain elusive in melanoma, although emerging data for adjuvant therapy indicate that interferon sensitivity is associated with ulceration of the primary melanoma. Intense investigation continues for clinical and biological markers that predict clinical benefit of immunotherapeutic drugs, such as interferon alfa or anti-CTLA4 antibodies, and the mechanisms that lead to resistance of targeted drugs.
Journal Article
Water Reservoirs in Small Planetary Bodies: Meteorites, Asteroids, and Comets
Asteroids and comets are the remnants of the swarm of planetesimals from which the planets ultimately formed, and they retain records of processes that operated prior to and during planet formation. They are also likely the sources of most of the water and other volatiles accreted by Earth. In this review, we discuss the nature and probable origins of asteroids and comets based on data from remote observations, in situ measurements by spacecraft, and laboratory analyses of meteorites derived from asteroids. The asteroidal parent bodies of meteorites formed
≤
4
Ma after Solar System formation while there was still a gas disk present. It seems increasingly likely that the parent bodies of meteorites spectroscopically linked with the E-, S-, M- and V-type asteroids formed sunward of Jupiter’s orbit, while those associated with C- and, possibly, D-type asteroids formed further out, beyond Jupiter but probably not beyond Saturn’s orbit. Comets formed further from the Sun than any of the meteorite parent bodies, and retain much higher abundances of interstellar material. CI and CM group meteorites are probably related to the most common C-type asteroids, and based on isotopic evidence they, rather than comets, are the most likely sources of the H and N accreted by the terrestrial planets. However, comets may have been major sources of the noble gases accreted by Earth and Venus. Possible constraints that these observations can place on models of giant planet formation and migration are explored.
Journal Article
Detection and spread of high pathogenicity avian influenza virus H5N1 in the Antarctic Region
Until recent events, the Antarctic was the only major geographical region in which high pathogenicity avian influenza virus (HPAIV) had never previously been detected. Here we report on the detection of clade 2.3.4.4b H5N1 HPAIV in the Antarctic and sub-Antarctic regions of South Georgia and the Falkland Islands, respectively. We initially detected H5N1 HPAIV in samples collected from brown skuas at Bird Island, South Georgia on 8th October 2023. Since this detection, mortalities were observed in several avian and mammalian species at multiple sites across South Georgia. Subsequent testing confirmed H5N1 HPAIV across several sampling locations in multiple avian species and two seal species. Simultaneously, we also confirmed H5N1 HPAIV in southern fulmar and black-browed albatross in the Falkland Islands. Genetic assessment of the virus indicates spread from South America, likely through movement of migratory birds. Critically, genetic assessment of sequences from mammalian species demonstrates no increased risk to human populations above that observed in other instances of mammalian infections globally. Here we describe the detection, species impact and genetic composition of the virus and propose both introductory routes and potential long-term impact on avian and mammalian species across the Antarctic region. We also speculate on the threat to specific populations following recent reports in the area.
High pathogenicity avian influenza virus has a wide host range and has been detected across a large geographic area. Here, the authors present evidence of spread to the Antarctic and sub-Antarctic regions, with signs of clinical infection and positive virus detection in birds and elephant seals.
Journal Article
Mitochondrial Fission, Fusion, and Stress
Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
Journal Article
The man in song : a discographic biography of Johnny Cash
\"There have been many books written about Johnny Cash, but The Man in Song is the first to examine Cash's incredible life through the lens of the songs he wrote and recorded. Music journalist and historian John Alexander has drawn on decades of studying Cash's music and life, from his difficult depression-era Arkansas childhood through his death in 2003, to tell a life story through songs familiar and obscure. In discovering why Cash wrote a given song or chose to record it, Alexander introduces readers anew to a man whose primary consideration of any song was the difference music makes in people's lives, and not whether the song would become a hit. The hits came, of course. Johnny Cash sold more than fifty million albums in forty years, and he holds the distinction of being the only performer inducted into the Rock and Roll Hall of Fame, the Country Music Hall of Fame, the Songwriters Hall of Fame, and the Gospel Music Hall of Fame. The Man in Song connects treasured songs to an incredible life. It explores the intertwined experience and creativity of childhood trauma. It rifles through the discography of a life: Cash's work with the Tennessee Two at Sam Phillips's Sun Studios, the unique concept albums Cash recorded for Columbia Records, the spiritual songs, the albums recorded live at prisons, songs about the love of his life, June Carter Cash, songs about murder and death and addiction, songs about ramblers, and even silly songs. Appropriate for both serious country and folk music enthusiasts and those just learning about this musical legend, The Man in Song will appeal to a fan base spanning generations. Here is a biography for those who first heard 'I Walk the Line' in 1956, a younger generation who discovered Cash through songs like his cover of Trent Reznor's 'Hurt, ' and everyone in between.\"-- Provided by publisher.
Book
Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination
Key Points
CTLA-4 regulates T-cell activation upon initiation of an immune response, in the lymphoid organs, where naive T cells are primed, and potentially in the periphery via regulatory T-cell (T
REG
) depletion
This diverse role of CTLA-4 in initiating and mounting immune responses might explain the plethora of immune-related adverse events (irAEs) experienced by patients receiving treatment with anti-CTLA-4 antibodies
PD-1 suppresses T-cell activity, mostly within the peripheral tissues and in the tumour microenvironment, which might explain the distinct spectrum and reduced incidence of adverse effects of anti-PD-1 antibodies
Thyroid disorders are more frequent adverse effects of treatment with anti-PD-1 antibodies (pembrolizumab and nivolumab) whereas colitis and hypophysitis are more frequent with anti-CTLA-4 antibodies (ipilimumab)
General guidelines on the management of irAEs recommend treatment of symptoms; corticosteroids are generally indicated together with dose skipping or discontinuation in patients with persistent grade ≥2 adverse events
Immune checkpoint inhibition is a novel approach to cancer treatment with enormous potential to improve the outcomes of patients with a range of malignancies. However, owing to this novel approach, a range of adverse events have emerged with different aetiologies to those of more conventional cancer treatments. In this Review, the authors describe the occurrence, and optimal management of adverse events resulting from use of immune checkpoint inhibitors.
Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.
Journal Article