Suzuki-Miyaura (SM) cross-coupling is arguably the most widely-applied transition metal catalysed carbon-carbon bond forming reaction to date. Its success originates from a combination of ...exceptionally mild and functional group tolerant reaction conditions, with a relatively stable, readily prepared and generally environmentally benign organoboron reagent. A variety of such reagents have been developed for the process, with properties that have been tailored for application under specific SM coupling conditions. This review analyses the seven main classes of boron reagent that have been developed. The general physical and chemical properties of each class of reagent are evaluated with special emphasis on the currently understood mechanisms of transmetalation. The methods to prepare each reagent are outlined, followed by example applications in SM coupling.
This review analyses the general physical and chemical properties of the seven main classes of boron reagent that have been employed for SM coupling.
Display omitted
•The global picture of chemical pollution in the environment is often fragmented.•This perspective highlights global picture of pollution regarding catastrophic risk.•Exposure related ...impact on fertility, cognition and food safety are discussed.•Prioritised strategies for curbing chemical dispersal are recommended.
Anthropogenic chemical pollution has the potential to pose one of the largest environmental threats to humanity, but global understanding of the issue remains fragmented. This article presents a comprehensive perspective of the threat of chemical pollution to humanity, emphasising male fertility, cognitive health and food security. There are serious gaps in our understanding of the scale of the threat and the risks posed by the dispersal, mixture and recombination of chemicals in the wider environment. Although some pollution control measures exist they are often not being adopted at the rate needed to avoid chronic and acute effects on human health now and in coming decades. There is an urgent need for enhanced global awareness and scientific scrutiny of the overall scale of risk posed by chemical usage, dispersal and disposal.
The transport of discarded electronic and electrical appliances (e-waste) to developing regions has received considerable attention, but it is difficult to assess the significance of this issue ...without a quantitative understanding of the amounts involved. The main objective of this study is to track the global transport of e-wastes by compiling and constraining existing estimates of the amount of e-waste generated domestically in each country M GEN, exported from countries belonging to the Organization for Economic Cooperation and Development (OECD) M EXP, and imported in countries outside of the OECD M IMP. Reference year is 2005 and all estimates are given with an uncertainty range. Estimates of M GEN obtained by apportioning a global total of ∼35,000 kt (range 20,000–50,000 kt) based on a nation’s gross domestic product agree well with independent estimates of M GEN for individual countries. Import estimates M IMP to the countries believed to be the major recipients of e-waste exports from the OECD globally (China, India, and five West African countries) suggests that ∼5,000 kt (3,600 kt–7,300 kt) may have been imported annually to these non-OECD countries alone, which represents ∼23% (17%–34%) of the amounts of e-waste generated domestically within the OECD. M EXP for each OECD country is then estimated by applying this fraction of 23% to its M GEN. By allocating each country’s M GEN, M IMP, M EXP and M NET = M GEN + M IMP – M EXP, we can map the global generation and flows of e-waste from OECD to non-OECD countries. While significant uncertainties remain, we note that estimated import into seven non-OECD countries alone are often at the higher end of estimates of exports from OECD countries.
Metal-organic frameworks (MOFs) have emerged over the past two decades as highly promising materials in the gas storage and separation arenas, with the potential to act as rapid uptake/rapid release ...sorbents for CO
2
, CH
4
and H
2
that may have significant impact in energy and sustainability technologies. However, a small but growing subset of the MOF community have been developing alternative, light-induced applications of MOFs. This review briefly outlines some of these exciting diversions from the 'traditional' applications of MOFs and focusses particularly on the design strategies of those frameworks that undergo photoinduced structural change. These strategies are classified as either (i) the imposition of photoresponsivity by a photoresponsive guest; (ii) post-synthetic modification (PSM) of frameworks to add in photoresponsive groups; (iii) synthesis of MOFs with linkers that support pendant photoresponsive groups; and, perhaps the most challenging, (iv) synthesis of MOFs from linkers that themselves have intrinsic structural photoresponsivity such that their structure is altered on illumination. Examples are given of each approach, future applications are proposed, and strategic pathways to next-generation photoresponsive frameworks are discussed.
Shedding light on the design strategies used to make structurally photoactive metal-organic frameworks.
Asteroseismic constraints on K giants make it possible to infer radii, masses and ages of tens of thousands of field stars. Tests against independent estimates of these properties are however scarce, ...especially in the metal-poor regime. Here, we report the detection of solar-like oscillations in eight stars belonging to the red-giant branch (RGB) and red-horizontal branch (RHB) of the globular cluster M4. The detections were made in photometric observations from the K2 Mission during its Campaign 2. Making use of independent constraints on the distance, we estimate masses of the eight stars by utilizing different combinations of seismic and non-seismic inputs. When introducing a correction to the Δν scaling relation as suggested by stellar models, for RGB stars we find excellent agreement with the expected masses from isochrone fitting, and with a distance modulus derived using independent methods. The offset with respect to independent masses is lower, or comparable with, the uncertainties on the average RGB mass (4–10 per cent, depending on the combination of constraints used). Our results lend confidence to asteroseismic masses in the metal-poor regime. We note that a larger sample will be needed to allow more stringent tests to be made of systematic uncertainties in all the observables (both seismic and non-seismic), and to explore the properties of RHB stars, and of different populations in the cluster.
A unified metrics toolkit has been developed to evaluate sustainability of reactions, encompassing a comprehensive and holistic range of criteria for measuring how green a reaction is, covering ...quantitative and qualitative criteria both upstream and downstream of the reaction itself. In addition, three new metrics are proposed, optimum efficiency (OE), renewable percentage (RP) and waste percentage (WP). The structure of the toolkit is tailored to give a level of detail and complexity commensurate with the stage of research, with an initial 'light-touch' appraisal at a few mg scale through to very in-depth analyses incorporating lifecycle considerations at large (multi-kg) scale. The toolkit additionally allows benchmarking of reactions against state-of-the-art in terms of their 'green credentials'. By promoting critical thinking in the user it also lends itself to being an educational tool, and its widespread adoption will support the training of a new generation of chemists to whom the use of greener and more sustainable techniques becomes second nature.
To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine.
Randomized, double-blind, ...parallel-group, clinical trial with a two-stage, adaptive, dose-ranging design. Patients were allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50, 100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The primary endpoint was pain relief (reduction to mild or none) 2 hours after dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain relief at 24 hours. A prespecified, blinded, automated interim analysis was used to discontinue randomization to less effective doses.
Per the adaptive study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were discontinued due to insufficient efficacy. For the remaining treatment groups, the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which compared the average 2-hour pain relief response proportion of the combined 300, 400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A generally similar efficacy pattern was seen for other endpoints. MK-0974 was generally well tolerated and there did not appear to be an increase in adverse events with increasing dose.
The novel, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.
Genomic testing and patient rights Jones, C Michael; Karp, Judith; Davis, Dena S
JNCI : Journal of the National Cancer Institute,
05/2024, Letnik:
116, Številka:
5
Journal Article
Despite the proclamation of a "postracial" society, racism in the United States remains "alive and sick" (S. P. Harrell, 2000), negatively impacting the physical, psychological, and emotional ...well-being of Black Americans. Moreover, the complex impact of racism throughout the life span is inadequately understood. Coping with the insidiousness of racism in its myriad forms requires recognizing how it expresses across development. In this developmental overview, we apply a life-course perspective (Gee, Walsemann, & Brondolo, 2012) to investigate racism-related stress and coping over time. Within each period of development, we first explore how racism-related stress may present for Black Americans and then document what coping from this stress looks like, highlighting extant strategies and interventions where they exist. This work concludes with a set of definitional, methodological, and clinical future directions and recommendations for improving the field's ability to mitigate the deleterious impact of racism-related stress.
Public Policy Relevance Statement
Racism is a pernicious stressor with the potential to disrupt the psychological health and well-being of Black Americans. Furthermore, racism-related stress operates in different ways, with different implications, at different times in development (childhood, adolescence, adulthood). To promote resilience in the face of and resistance to racism, it is critical to understand its various presentations, as well as culturally relevant ways to cope with and heal from racism-related stressors.
Stars which pass close to the Sun can perturb the Oort cloud, injecting comets into the inner solar system where they may collide with the Earth. Using van Leeuwen’s re-reduction of the Hipparcos ...data complemented by the original Hipparcos and Tycho-2 catalogues, along with recent radial velocity surveys, I integrate the orbits of over 50 000 stars through the Galaxy to look for close encounters. The search uses a Monte Carlo sampling of the covariance of the data in order to properly characterize the uncertainties in the times, distances, and speeds of the encounters. I show that modelling stellar encounters by assuming instead a linear relative motion produces, for many encounters, inaccurate and biased results. I find 42, 14, and 4 stars which have encounter distances below 2, 1, and 0.5 pc respectively, although some of these stars have questionable data. Of the 14 stars coming within 1 pc, 5 were found by at least one of three previous studies (which found a total of 7 coming within 1 pc). The closest encounter appears to be Hip 85605, a K or M star, which has a 90% probability of coming between 0.04 and 0.20 pc between 240 and 470 kyr from now (90% Bayesian confidence interval). However, its astrometry may be incorrect, in which case the closest encounter found is the K7 dwarf GL 710, which has a 90% probability of coming within 0.10–0.44 pc in about 1.3 Myr. A larger perturbation may have been caused by gamma Microscopii, a G6 giant with a mass of about 2.5 M⊙, which came within 0.35–1.34 pc (90% confidence interval) around 3.8 Myr ago.
PDF
