While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

A new mineral species, mikenewite (IMA2022-102), ideally Mn2+(S4+O3)⋅3H2O, has been discovered from the San Judas Chimney, Ojuela mine, Mapimí, Durango, Mexico. It occurs as spheres of platy crystals. Associated minerals include goethite, cryptomelane, adamite and lotharmeyerite. Mikenewite is yellowish in transmitted light, transparent with a white streak and vitreous lustre. It is brittle and has a Mohs hardness of 2½–3. Cleavage is perfect on {101}. The measured and calculated densities are 2.48(5) and 2.467 g/cm3, respectively. Optically, mikenewite is biaxial (+), with α = 1.606(5), β = 1.614(5), γ = 1.627(1) (white light), 2V(meas.) = 69(3)° and 2V(calc.) = 77°. An electron microprobe analysis yielded an empirical formula (based on 6 O apfu) of (Mn0.86Zn0.12Fe0.04Ca0.02)Σ1.04(S0.98O3)⋅3H2O, which can be simplified to (Mn,Zn,Fe)(SO3)⋅3H2O.

Mikenewite is the natural analogue of synthetic α-Mn2+(S4+O3)⋅3H2O, as well as the Mn-analogue of albertiniite, Fe2+(S4+O3)⋅3H2O. It is monoclinic, with space group P21/n and unit-cell parameters a = 6.6390(3), b = 8.8895(4), c = 8.7900(4) Å, β = 96.095(2)°, V = 515.83(4) Å3 and Z = 4. The crystal structure of mikenewite is characterised by each Mn atom coordinated octahedrally by six O atoms, three from different sulfite O atoms and three from H2O molecules. Each S4+O3 group is bonded to three Mn atoms, resulting in a sheet parallel to (101) with the sheet composition of Mn2+(S4+O3)⋅3H2O. Such sheets, stacked along [10$\bar{1}$], are joined together by hydrogen bonds, accounting for the perfect cleavage of the mineral. Mikenewite is dimorphous with orthorhombic Pnma gravegliaite, as albertiniite is with fleisstalite. Its discovery from the Ojuela mine, which is particularly rich in Zn, implies the possibility of finding Zn-bearing sulfites there as well.

A new mineral species, bernardevansite (IMA2022-057), ideally Al2(Se4+O3)3⋅6H2O, has been discovered from the El Dragón mine, Potosí Department, Bolivia. It occurs as aggregates or spheres of radiating bladed crystals on a matrix consisting of Co-bearing krut'aite–penroseite. Associated minerals are Co-bearing krut'aite–penroseite, chalcomenite and ‘clinochalcomenite’. Bernardevansite is colourless in transmitted light, transparent with white streak and vitreous lustre. It is brittle and has a Mohs hardness of 2½–3. Cleavage is not observed. The measured and calculated densities are 2.93(5) and 2.997 g/cm3, respectively. Optically, bernardevansite is biaxial (+), with α = 1.642(5), β = 1.686(5) and γ = 1.74(1) (white light). An electron microprobe analysis yielded an empirical formula (based on 15 O apfu) (Al1.26Fe3+0.82)Σ2.08(Se0.98O3)3⋅6H2O, which can be simplified to (Al,Fe3+)2(SeO3)3⋅6H2O.

Bernardevansite is the Al-analogue of mandarinoite, Fe3+2(SeO3)3⋅6H2O or dimorphous with P$\bar{6}$2c alfredopetrovite. It is monoclinic, with space group P21/c and unit-cell parameters a = 16.5016(5), b = 7.7703(2), c = 9.8524(3) Å, β = 98.258(3)°, V = 1250.21(6) Å3 and Z = 4. The crystal structure of bernardevansite consists of a corner-sharing framework of M3+O6 (M = Al and Fe) octahedra and Se4+O3 trigonal pyramids, leaving large voids occupied by the H2O groups. There are two unique M3+ positions: M1 is octahedrally coordinated by (4O + 2H2O) and M2 by (5O + H2O). The structure refinement indicates that Al preferentially occupies M1 (= 0.692Al + 0.308Fe) over M2 (= 0.516Al + 0.484Fe). The substitution of the majority of Fe in mandarinoite by Al results in a significant reduction in its unit-cell volume from 1313.4 Å3 to 1250.21(6) Å3 for bernardevansite. The discovery of bernardevansite begs the question whether the Fe3+ end-member, Fe3+2(SeO3)3⋅6H2O, has two polymorphs as well, one with P21/c symmetry, as for mandarinoite and the other P$\bar{6}$2c, as for alfredopetrovite.

ABSTRACT IMPACT: Improved radiation treatment will yield higher doses at the tumor site, while reducing damage to healthy tissue, which will improve clinical outcomes. OBJECTIVES/GOALS: Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized and the mechanism uncovered. The efficacy of these particles will be tested in a murine system. METHODS/STUDY POPULATION: Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol then covalently conjugated to chlorin e6, a known, FDA approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species following X-irradiation was measured. Enhanced cell killing was measured clonogenically and in vivo efficacy and tumor pathology was assessed in a murine system. Further studies will determine the optimum combination of particle shape, photosensitizer structure, and ratio of components, as well as the optimal dosing schedule. RESULTS/ANTICIPATED RESULTS: Conjugation of the particle to the photosensitizer was successfully achieved, and the molecule was detectable by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates significantly increased cell killing during radiation treatment, while neither the particle alone or the photosensitizer significantly affected clonogenic survival at the same concentrations. Pathology of breast tumors grown in immunocompetent mice showed a significant increase in necrotic tissue following a single 20 gy treatment when the conjugate was present. DISCUSSION/SIGNIFICANCE OF FINDINGS: Radiation therapy is widely used clinically and it is a highly localized form of treatment. However, the total dose of radiation is limited largely to prevent injury to adjacent normal tissue. This conjugate has the potential to increase the effective dose in the tumor thereby reducing damage to healthy tissue and providing a more effective therapy.

The studied seep carbonates from Tsushima, Japan, are embedded within marine siliciclastics of the lower Miocene Taishu Group and represent the earliest evidence of hydrocarbon seepage in the Sea of Japan. In contrast to Miocene and Pliocene examples from Honshu, which are often found above anticlines, the seeps from Tsushima formed within a pull-apart basin before major anticlines had formed. The three carbonates from Fukuzaki, Kanoura and Tanohama are composed chiefly of calcite, with significant admixture of ankerite only at Kanoura. The stable carbon isotope composition of calcites (δ13C as low as −40.2 ‰ VPDB for Fukuzaki, −41.8 ‰ VPDB for Kanoura, and −52.8 ‰ VPDB for Tanohama) indicate methanogenic origin of the carbonates. Textures of these deposits, including radiaxial and yellow cements, are indicative of formation at a methane seep. The stable oxygen isotope composition of calcites (δ18O values as low as −14.4 ‰ VPDB for Fukuzaki, −14.5 ‰ VPDB for Kanoura and −13.9 ‰ VPDB for Tanohama) indicate that they were influenced by burial fluids. Burial diagenesis is also indicated by the stable isotopic compositions of ankerite (δ13C ranging from −19.1 ‰ to −7.1 ‰ VPDB, δ18O from −11.1 ‰ to −9.7 ‰ VPDB). Molecular fossils from Tanohama comprise n-alkanes with short-chain predominance, interpreted to have formed due to thermal cracking of organic matter. The carbonates yield a chemosynthesis-based community comprising vesicomyids Pleurophopsis chitanii, P. cf. hamuroi, the bathymodiolin ‘Bathymodiolus’ akanudaensis, the lucinid Lucinoma sp. and the provannid Provanna? sp., which have never been hitherto identified. ‘Bathymodiolus’ akanudaensis, Lucinoma sp. and Provanna? sp. are the oldest records of these taxa in the Sea of Japan.

OBJECTIVES/GOALS:

• Development of gold nanoparticles covalently linked to a photosensitizer for use to enhance radiation therapy. The particles will be thoroughly characterized structurally and mechanistically. The gold particles should enhance radiation activity by closer proximity to the photosensitizer and by increasing particle accumulation in the tumor.

METHODS/STUDY POPULATION:

• Gold nanoparticles were synthesized and coated with amine-terminated poly(ethylene) glycol, then covalently conjugated to chlorin e6, a known FDA-approved photosensitizer. The system was characterized using UV-Vis spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. The generation of reactive oxygen species was measured after X-irradiation. Enhanced cell killing was evaluated clonogenically in addition to assessment of in vivo efficacy and tumor pathology.

RESULTS/ANTICIPATED RESULTS:

• Conjugation of the particle to the photosensitizer was achieved, and the molecule was detected by UV-Vis spectroscopy. TEM and NTA showed no aggregation of the particles, and an increase in reactive oxygen species generation was observed. The conjugates increased cell killing during radiation treatment, whereas neither the particle alone nor the photosensitizer significantly affected clonogenic survival at the same concentrations. Breast tumors grown in immunocompetent mice showed increased necrotic tissue after a single 20 gy treatment in the presence of the conjugate.

DISCUSSION/SIGNIFICANCE OF IMPACT: Radiation therapy is widely used clinically, but dosage is limited largely to prevent injury to adjacent normal tissue. By increasing the local effect of radiation therapy, our gold conjugate has the potential to augment the effective radiation dose in the tumor, thereby reducing damage to healthy tissue and providing a more effective therapy.

Replicate radiocarbon (14C) measurements of organic and inorganic control samples, with known Fraction Modern values in the range Fm = 0–1.5 and mass range 6 μg–2 mg carbon, are used to determine both the mass and radiocarbon content of the blank carbon introduced during sample processing and measurement in our laboratory. These data are used to model, separately for organic and inorganic samples, the blank contribution and subsequently “blank correct” measured unknowns in the mass range 25–100 μg. Data, formulas, and an assessment of the precision and accuracy of the blank correction are presented.

Recent commercialization of auxin herbicide–based weed control systems has led to increased off-target exposure of susceptible cotton cultivars to auxin herbicides. Off-target deposition of dilute concentrations of auxin herbicides can occur on cotton at any stage of growth. Field experiments were conducted at two locations in Mississippi from 2014 to 2016 to assess the response of cotton at various growth stages after exposure to a sublethal 2,4-D concentration of 8.3 g ae ha−1. Herbicide applications occurred weekly from 0 to 14 weeks after emergence (WAE). Cotton exposure to 2,4-D at 2 to 9 WAE resulted in up to 64% visible injury, whereas 2,4-D exposure 5 to 6 WAE resulted in machine-harvested yield reductions of 18% to 21%. Cotton maturity was delayed after exposure 2 to 10 WAE, and height was increased from exposure 6 to 9 WAE due to decreased fruit set after exposure. Total hand-harvested yield was reduced from 2,4-D exposure 3, 5 to 8, and 13 WAE. Growth stage at time of exposure influenced the distribution of yield by node and position. Yield on lower and inner fruiting sites generally decreased from exposure, and yield partitioned to vegetative or aborted positions and upper fruiting sites increased. Reductions in gin turnout, micronaire, fiber length, fiber-length uniformity, and fiber elongation were observed after exposure at certain growth stages, but the overall effects on fiber properties were small. These results indicate that cotton is most sensitive to low concentrations of 2,4-D during late vegetative and squaring growth stages.

Methods for identifying relevant policy impacts for valuation in benefit-cost analyses (BCAs) have received relatively little attention in academic research, applied policy analyses, and guidance documents. In this paper, we develop a systematic, transparent, and replicable process that draws upon information contained in records of Congressional hearings to identify relevant policy impacts for valuation in a BCA. Our approach involves classifying – and subsequently analyzing – statements from witnesses testifying in Congressional hearings on the topic of the BCA. By using Congressional hearings as the basis for our approach, we are identifying potential policy impacts from information provided during the very process the BCA is intended to inform. However, because this approach is quite resource-intensive and would be somewhat burdensome for agencies to implement, it may be best applied in the academic realm, with identified impacts resulting from such applications then made available to agency personnel for potential inclusion in BCAs. Using the case of the Glen Canyon Dam, we demonstrate the approach and its resulting improvements in the quality and transparency of the BCA it was intended to inform.

The introduction of auxin herbicide weed control systems has led to increased occurrence of crop injury in susceptible soybeans and cotton. Off-target exposure to sublethal concentrations of dicamba can occur at varying growth stages, which may affect crop response. Field experiments were conducted in Mississippi in 2014, 2015, and 2016 to characterize cotton response to a sublethal concentration of dicamba equivalent to 1/16X the labeled rate. Weekly applications of dicamba at 35 g ae ha−1 were made to separate sets of replicated plots immediately following planting until 14 wk after emergence (WAE). Exposure to dicamba from 1 to 9 WAE resulted in up to 32% visible injury, and exposure from 7 to 10 WAE delayed crop maturity. Exposure from 8 to 10 and 13 WAE led to increased cotton height, while an 18% reduction in machine-harvested yield resulted from exposure at 6 WAE. Cotton exposure at 3 to 9 WAE reduced the seed cotton weight partitioned to position 1 fruiting sites, while exposure at 3 to 6 WAE also reduced yield in position 2 fruiting sites. Exposure at 2, 3, and 5 to 7 WAE increased the percent of yield partitioned to vegetative branches. An increase in percent of yield partitioned to plants with aborted terminals occurred following exposure from 3 to 7 WAE and corresponded with reciprocal decreases in yield partitioned to positional fruiting sites. Minimal effects were observed on fiber quality, except for decreases in fiber length uniformity resulting from exposure at 9 and 10 WAE.

Five species of bivalves and two species of gastropods are described from late Selandian to earliest Thanetian wood-fall communities from the Katsuhira Formation in Urahoro Town, eastern Hokkaido, northern Japan. Three bivalves and two gastropods are new to science: Thyasira (Thyasira) oliveri Amano and Jenkins, new species, Astarte (Astarte) paleocenica Amano and Jenkins, new species, Poromya katsuhiraensis Amano and Jenkins, new species, Neverita majimai Amano and Jenkins, new species, and Biplica paleocenica Amano and Jenkins, new species. Poromya katsuhiraensis n. sp. and Neverita majimai n. sp. are the earliest records of their genus. Astarte paleocenica n. sp. is the last species before the genus disappeared from the northern Pacific region during the Eocene, only to reappear with the opening of the Bering Strait during the latest Miocene. Moreover, two bivalve species and one gastropod genus are Cretaceous relict forms: Propeamussium yubarense (Yabe and Nagao, 1928), Myrtea ezoensis (Nagao, 1938), and Biplica Popenoe, 1957. These species and other relict protobranch bivalves had wide geographical ranges in the deep sea during the Cretaceous, which helped them to survive the end-Cretaceous mass extinction. The chemosynthesis-based species Bathyacmaea? sp., Myrtea ezoensis, and Thyasira oliveri n. sp. were recovered, but small bathymodioline mussels have not been found. This confirms that the small deep-sea mussels did not appear in the wood-fall communities at least by the earliest Thanetian.

UUID: http://zoobank.org/125bd4ab-b172-43d9-80b9-57b75a805150

Four new species of the methane seep-inhabiting kalenterid bivalve genus Caspiconcha Kelly in Kelly et al., 2000 are described: Caspiconcha basquensis from the late Albian of northern Spain, C. yubariensis from the late Albian of northern Japan, C. raukumaraensis from the late Albian to mid-Cenomanian of New Zealand, and C. lastsamurai from the Campanian of northern Japan. The earliest confirmed record of the genus is known from the latest Jurassic. It reached its maximum diversity in the Albian and declined in diversity and abundance through the Late Cretaceous. The youngest species, C. lastsamurai, is currently known from a single specimen only.

UUID: http://zoobank.org/2f84cfd3-216c-4f1b-8c9f-c808a47f7aaa

Quasi-stationary distributions (QSDs) arise from stochastic processes that exhibit transient equilibrium behaviour on the way to absorption. QSDs are often mathematically intractable and even drawing samples from them is not straightforward. In this paper the framework of sequential Monte Carlo samplers is utilised to simulate QSDs and several novel resampling techniques are proposed to accommodate models with reducible state spaces, with particular focus on preserving particle diversity on discrete spaces. Finally, an approach is considered to estimate eigenvalues associated with QSDs, such as the decay parameter.

The spread of noxious weeds on rangeland and forests in the United States has been described as a raging biological wildfire. This analogy applies to aspects of spread, impact, and control of weeds. Patterns and means of spread are similar. Noxious weeds and wildfires can dramatically change natural plant communities, alter distribution and species composition of wildlife populations, damage watersheds and increase soil erosion, and adversely affect recreation and aesthetic values. Wildfire management involves prevention, early detection, timely control, and site rehabilitation; elements which are also the foundation of sound weed management. Principles and practices associated with wildfire suppression can be used to illustrate many weed science fundamentals, and to improve weed management programs. Federal land management agencies are directed to train employees in effective weed management and to increase public awareness about noxious weeds. Most agency employees are familiar with wildfire management; knowledge which could be useful in teaching weed management principles. Fire prevention could serve as a model to promote greater public awareness of the impact of noxious weeds and the need for weed prevention and early detection.

The Internet offers a number of advantages as a survey mode: low marginal cost per completed response, capabilities for providing respondents with large quantities of information, speed, and elimination of interviewer bias. Those seeking these advantages confront the problem of representativeness both in terms of coverage of the population and capabilities for drawing random samples. Two major strategies have been pursued commercially to develop the Internet as a survey mode. One strategy, used by Harris Interactive, involves assembling a large panel of willing respondents who can be sampled. Another strategy, used by Knowledge Networks, involves using random digit dialing (RDD) telephone methods to recruit households to a panel of Web-TV enabled respondents. Do these panels adequately deal with the problem of representativeness to be useful in political science research? The authors address this question with results from parallel surveys on global climate change and the Kyoto Protocol administered by telephone to a national probability sample and by Internet to samples of the Harris Interactive and Knowledge Networks panels. Knowledge and opinion questions generally show statistically significant but substantively modest difference across the modes. With inclusion of standard demographic controls, typical relational models of interest to political scientists produce similar estimates of parameters across modes. It thus appears that, with appropriate weighting, samples from these panels are sufficiently representative of the U.S. population to be reasonable alternatives in many applications to samples gathered through RDD telephone surveys.