Sequential Lonsdaleite to Diamond Formation in Ureilite Meteorites via In Situ Chemical Fluid/Vapor Deposition.

Ureilite meteorites are arguably our only large suite of samples from the mantle of a dwarf planet and typically contain greater abundances of diamond than any known rock. Some also contain lonsdaleite, which may be harder than diamond. Here, we use electron microscopy to map the relative distribution of coexisting lonsdaleite, diamond, and graphite in ureilites. These maps show that lonsdaleite tends to occur as polycrystalline grains, sometimes with distinctive fold morphologies, partially replaced by diamond + graphite in rims and cross-cutting veins. These observations provide strong evidence for how the carbon phases formed in ureilites, which, despite much conjecture and seemingly conflicting observations, has not been resolved. We suggest that lonsdaleite formed by pseudomorphic replacement of primary graphite shapes, facilitated by a supercritical C-H-O-S fluid during rapid decompression and cooling. Diamond + graphite formed after lonsdaleite via ongoing reaction with C-H-O-S gas. This graphite > lonsdaleite > diamond + graphite formation process is akin to industrial chemical vapor deposition but operates at higher pressure (∼1-100 bar) and provides a pathway toward manufacture of shaped lonsdaleite for industrial application. It also provides a unique model for ureilites that can reconcile all conflicting observations relating to diamond formation.

Small molecule. Big biology. Dual phosphatase inhibitor enters the immunotherapy fray.

The advent and clinical success of immune checkpoint inhibitors Ipilimumab, Nivolumab and Pembrolizumab has had a seismic impact on our drug discovery focus and rationale. Novel extrinsic targets that enhance immune responses to cancer are actively being pursued, while tumor intrinsic targets that render cancer cells more sensitive to the immune system have joined traditional intrinsic targets (e.g. directly cytotoxic) in the drug discovery pipeline. The phosphatase PTPN2 (TC-PTP) and its paralog PTPN1 (PTP-1B) are negative regulators of several cytokine signaling pathways and T cell receptor (TCR) signaling. In a recent publication, Baumgartner et al. demonstrate the pre-clinical efficacy of a first-in-class dual PTPN1/N2 active site inhibitor (ABBV-CLS-484/AC484) in cancer models.

Invasive fungal sinusitis: A comparison of pediatric versus adult cases.

BACKGROUND: Invasive fungal sinusitis (IFS) is a rare infection with high mortality, mainly impacting immunocompromised patients. Given its significant mortality, timely recognition and treatment is crucial. This study aims to highlight the differences in presentation of IFS between pediatric and adult patients to aid in prompt diagnosis and treatment of this condition. METHODS: A comprehensive literature search of PubMed, EMBASE, Web of Science, Global Index Medicus, Global Health (EBSCO) and Cochrane Database of Systematic Reviews was conducted to identify articles relating to IFS. Patient demographics, comorbidities, presentation, disease characteristics, treatments and outcomes were extracted from the studies, and statistical analyses were conducted to compare these variables between pediatric and adult patients. RESULTS: 111 studies identified 22 pediatric and 132 adult patients worldwide. Children were more likely to have hematologic malignancies compared to adults (59.1 % vs. 15.2 %, p < 0.001). Facial symptoms such as pain, edema, and numbness were the most common symptoms for both age groups. In the pediatric population, fever and nasal or oral mucosal lesions were more common presenting symptoms (both p < 0.001). Pediatric patients were more likely to present without disease extension beyond the sinuses (p < 0.001). There was no significant difference in either medication treatment or mortality between the two cohorts. CONCLUSION: IFS often presents with non-specific symptoms and a unique presentation in pediatric and adult populations. Clinical awareness of the varying presentations in both populations is important to treat in a timely manner given the rapid progression and high mortality rates of IFS.

A Core Outcome Set for Seamless, Standardized Evaluation of Innovative Surgical Procedures and Devices (COHESIVE): A Patient and Professional Stakeholder Consensus Study.

OBJECTIVE: To develop a COS, an agreed minimum set of outcomes to measure and report in all studies evaluating the introduction and evaluation of novel surgical techniques. SUMMARY OF BACKGROUND DATA: Agreement on the key outcomes to measure and report for safe and efficient surgical innovation is lacking, hindering transparency and risking patient harm. METHODS: (I) Generation of a list of outcome domains from published innovation-specific literature, policy/regulatory body documents, and surgeon interviews; (II) Prioritization of identified outcome domains using an international, multi-stakeholder Delphi survey; (III) Consensus meeting to agree the final COS. Participants were international stakeholders, including patients/public, surgeons, device manufacturers, regulators, trialists, methodologists, and journal editors. RESULTS: A total of 7972 verbatim outcomes were identified, categorized into 32 domains, and formatted into survey items/questions. Four hundred ten international participants (220 professionals, 190 patients/public) completed at least one round 1 survey item, of which 153 (69.5%) professionals and 116 (61.1%) patients completed at least one round 2 item. Twelve outcomes were scored "consensus in" ("very important" by ≥70% of patients and professionals) and 20 "no consensus." A consensus meeting, involvingcontext: modifications, unexpected disadvantages, device problems, technical procedure completion success, patients' experience relating to the procedure being innovative, surgeons'/operators' experience. Other domains relate to intended benefits, whether the overall desired effect was achieved and expected disadvantages. CONCLUSIONS: The COS is recommended for use in all studies before definitive randomized controlled trial evaluation to promote safe, transparent, and efficient surgical innovation.

Genotype accounts for intraspecific variation in the timing and duration of multiple, sequential life-cycle events in a willow species.

PREMISE: Phenological variation among individuals within populations is common and has a variety of ecological and evolutionary consequences, including forming the basis for population-level responses to environmental change. Although the timing of life-cycle events has genetic underpinnings, whether intraspecific variation in the duration of life-cycle events reflects genetic differences among individuals is poorly understood. METHODS: We used a common garden experiment with 10 genotypes of Salix hookeriana (coastal willow) from northern California, United States to investigate the extent to which genetic variation explains intraspecific variation in the timing and duration of multiple, sequential life-cycle events: flowering, leaf budbreak, leaf expansion, fruiting, and fall leaf coloration. We used seven clones of each genotype, for a total of 70 individual trees. RESULTS: Genotype affected each sequential life-cycle event independently and explained on average 62% of the variation in the timing and duration of vegetative and reproductive life-cycle events. All events were significantly heritable. A single genotype tended to be "early" or "late" across life-cycle events, but for event durations, there was no consistent response within genotypes. CONCLUSIONS: This research demonstrates that genetic variation can be a major component underlying intraspecific variation in the timing and duration of life-cycle events. It is often assumed that the environment affects durations, but we show that genetic factors also play a role. Because the timing and duration of events are independent of one another, our results suggest that the effects of environmental change on one event will not necessarily cascade to subsequent events.

Effectiveness of Lay Bystander Hands-Only Cardiopulmonary Resuscitation on a Mattress versus the Floor: A Randomized Cross-Over Trial.

STUDY OBJECTIVE: Bystander cardiopulmonary resuscitation increases the likelihood of out-of-hospital cardiac arrest survival by more than two-fold. A common barrier to the prompt initiation of compressions is moving victims to the floor, but compression quality on a "floor" versus a "mattress" has not been tested among lay bystanders. METHODS: We conducted a prospective, randomized, cross-over trial comparing lay bystander compression quality using a manikin on a bed versus the floor. Participants included adults without professional health care training. We randomized participants to the order of manikin placement, either on a mattress or on the floor. For both, participants were instructed to perform 2 minutes of chest compressions on a cardiopulmonary resuscitation Simon manikin Gaumard (Gaumard Scientific, Miami, FL). The primary outcome was mean compression depth (cm) over 2 minutes. We fit a linear regression model adjusted for scenario order, age, sex, and body mass index with robust standard errors to account for repeated measures and reported mean differences with 95% confidence intervals (CIs). RESULTS: Our sample of 80 adults was 66% female with a mean age of 50.5 years (SD 18.2). The mean compression depth on the mattress was 2.9 cm (SD 2.3) and 3.5 cm (SD 2.2) on the floor, a mean difference of 0.58 cm (95% CI 0.18, 0.98). Compression depth fell below the 5 to 6 cm depth recommended by the American Heart Association on both surfaces. In the adjusted model, the mean depth was greater when the manikin was on the floor than the mattress (adjusted mean difference 0.62 cm; 95% CI 0.23 to 1.01), and mean depth was less for females than males (adjusted mean difference -1.42 cm, 95% CI -2.59, -0.25). In addition, the difference in compression depth was larger for female participants (mean difference 0.94 cm; 95% CI 0.54, 1.34) than for male participants (mean difference -0.01 cm; 95% CI -0.80, 0.78), and the interaction was statistically significant (P = .04). CONCLUSION: The mean compression depth was significantly smaller on the mattress and with female bystanders. Further research is needed to understand the benefit of moving out-of-hospital cardiac arrest victims to the floor relative to the detrimental effect of delaying chest compressions.

Words That Bind: Moral Obligation, Textual Epistemology, and Globalizing Legal Power.

In this review essay, we probe three main elements of Laura Ford's Intellectual Property of Nations: her discussion of the structure of moral obligation and its materialization via writing and the institutions of the law; reflections on how the book intersects with questions of textual epistemology (especially the question of inferring intent from texts); and, finally, a self-consciously "presentist" discussion of how the book's findings intersect with our modern world of global legal regimes.

Influence of fuel structure derived from terrestrial laser scanning (TLS) on wildfire severity in logged forests.

CONTEXT: Logging and wildfire can reduce the height of the forest canopy and the distance to the understorey vegetation below. These conditions may increase the likelihood of high severity wildfire (canopy scorch or consumption), which may explain the greater prevalence of high severity wildfire in some recently logged or burnt forests. However, the effects of these structural characteristics on wildfire severity have not clearly been demonstrated. OBJECTIVES: We aimed to assess how the structure of forests affected by logging and wildfire influence the probability of high severity wildfire. METHODS: We used terrestrial laser scanning to measure the connectivity of canopy and understorey vegetation in forests at various stages of recovery after logging and wildfire (approximately 0-80 years since disturbance). These sites were subsequently burnt by mixed severity wildfire during the 2019-20 'Black Summer' fire season in south-eastern Australia. We assessed how these forest structure metrics affected the probability of high severity wildfire. RESULTS: The probability of high severity fire decreased as the canopy base height increased, and the distance between the canopy base and understorey increased. High severity wildfire was less likely in forests with taller understoreys and greater canopy or understorey cover, but these effects were not considered causal. Fire weather was the strongest driver of wildfire severity, which was also affected by topography. CONCLUSIONS: These findings demonstrate a link between forest structure characteristics, that are strongly shaped by antecedent logging and fire, and fire severity. They also indicate that vertical fuel structure should be incorporated into assessments of fire risk.

Death receptor signal transducers: nodes of coordination in immune signaling networks.

Death receptors (DRs) are members of the tumor necrosis factor receptor superfamily that possess a cytoplasmic death domain (DD). DRs regulate important operational and homeostatic aspects of the immune system. They transmit signals through apical protein complexes, which are nucleated by the DD adaptors FADD and TRADD, to control cellular outcomes that range from apoptosis to gene activation. FADD and TRADD also nucleate several distal signaling complexes, which mediate cross-talk between distinct DR signaling pathways. Moreover, together with other DR signal transducers, FADD and TRADD participate in functional complexes assembled by certain non-DR immune cell receptors, such as pattern-recognition receptors. Thus, DR signal transducers may provide important nodes of coordination in immune signaling networks.

Intimate partner violence and maternal health services utilization: evidence from 36 National Household Surveys.

BACKGROUND: High rates of maternal mortality and intimate partner violence (IPV) are both major worldwide health challenges. Evidence from single-country samples suggests that IPV may be an important risk factor for low utilization of maternal health services, but there is little large-scale evidence on this association. This paper evaluates whether IPV is a risk factor for low utilization of maternal health services in a large cross-country sample, and also compiles evidence on the relative effects of different forms of IPV. METHODS: We analyze the association between intimate partner violence and utilization of maternal health care, using a dataset compiling all Demographic and Health Surveys that report data on intimate partner violence. Using data on 166,685 women observed in 36 countries between 2005 and 2016, we estimate logistic regression models to analyze the relationship between lifetime experience of IPV and utilization of antenatal care (ANC), facility delivery care, and postnatal care. We estimate both unadjusted models and models adjusted for geographic and sociodemographic characteristics that are generally correlated with utilization of maternal health care (including age, education, number of children, wealth status, marital status, and urbanity). RESULTS: Lifetime experience of any IPV is associated with decreased use of maternal health services in a broad sample of births observed in lower and middle-income countries: in particular, the utilization of four or more ANC visits, the number of ANC visits, and the utilization of facility care at birth. This association remains statistically significant even after adjusting for country of residence, subnational region of residence, and additional individual-level covariates; however, there is no statistically significant association between experience of any IPV and postnatal care. The only form of IPV significantly associated with care utilization is physical IPV. CONCLUSIONS: Women experiencing physical intimate partner violence show lower levels of utilization of maternal health services in a large sample of developing and middle-income countries. Given that reduced utilization of maternal health services is correlated with maternal and neonatal health outcomes, this pattern suggests that IPV prevention may be an important component of interventions targeting enhanced maternal and neonatal health.

Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells.

The importance of conventional dendritic cells (cDCs) in the processing and presentation of antigen is well established, but the contribution of plasmacytoid dendritic cells (pDCs) to these processes, and hence to T cell immunity, remains unclear. Here we showed that unlike cDCs, pDCs continued to synthesize major histocompatibility complex (MHC) class II molecules and the MHC class II ubiquitin ligase MARCH1 long after activation. Sustained MHC class II-peptide complex formation, ubiquitination and turnover rendered pDCs inefficient in the presentation of exogenous antigens but enabled pDCs to continuously present endogenous viral antigens in their activated state. As the antigen-presenting abilities of cDCs and pDCs are fundamentally distinct, these two cell types may activate largely nonoverlapping repertoires of CD4(+) T cells.

Framing Flexible Spending Accounts: A Large-Scale Field Experiment on Communicating the Return on Medical Savings Accounts.

Tax-preferred health savings devices such as Flexible Spending Accounts (FSAs) and Health Savings Accounts (HSAs) offer employees potentially valuable financial instruments for directing pre-tax earnings to eligible medical expenses. Despite their increasing popularity as an employee benefit, however, there is little causal evidence around individual demand for these accounts. This paper seeks to address this gap in the literature, reporting on a randomized controlled field experiment conducted with over 11,000 U. S federal employees in 2017 in order to evaluate the effectiveness of targeted messages designed to increase FSA contributions. Our results suggest that the provision of basic information about FSAs delivered via an emailed employee newsletter did not affect the likelihood of contribution or the contribution level. The addition of statements about the absolute returns or relative returns offered by the accounts similarly had no significant effects, and these null effects are observed despite relatively high email open rates. We discuss explanations for the null results and the policy implications of findings from what appears to be the first health economics experiment analyzing tax incentives around health care savings.

Demand for self-tests: Evidence from a Becker-DeGroot-Marschak mechanism field experiment.

Self-tests offer one approach for reducing frictions underlying low demand for preventive health inputs, yet there is little evidence on demand for self-tests. We used the Becker-DeGroot-Marschak mechanism-an incentive-compatible approach-to elicit exact willingness to pay (WTP) for HIV self-tests in a field experiment with 822 participants at 66 health clinics/pharmacies in Kenya. Our analysis reveals substantial demand at low prices and highly elastic demand at a wide range of prices above this range. We find few participants with nonpositive WTP. We examine correlates of WTP and discuss policy and research implications of our findings.

Observations on the Early Stages of Corrosion on AA2099-T83.

An Al­Cu­Li aerospace alloy has been investigated to determine the order in which corrosion at different types of sites occurs in AA2099-T83. Specifically, the sequence of galvanic attack on intermetallic (IM) particles and other sites of AA2099-T83 was determined as a function of time, in 0.1 M NaCl, through the use of scanning electron microscopy and electron backscatter diffraction characterization techniques. The earliest attack occurred at isolated grains and grain boundaries and on Li-containing dispersoids. Similarly, some constituent IM particles showed evidence of trenching in the surrounding alloy matrix. These IM particles included Al7Cu2Fe and another group of unidentified particles which displayed complete trenching within the first 10 min of exposure. Al13(Fe, Mn)4 were next most active followed by Al37Fe12Cu2 with Al6(Fe,Mn) and large TiB2 particles being the least active.

The Impact of Chemical Bonding on Mass Absorption Coefficients of Soft X-rays.

Accurate elemental quantification of materials by X-ray detection techniques in electron microscopes or microprobes can only be carried out if the appropriate mass absorption coefficients (MACs) are known. With continuous advancements in experimental techniques, databases of MACs must be expanded in order to account for new detection limits. Soft X-ray emission spectroscopy (SXES) is a characterization technique that can detect emitted X-rays whose energies are in the range of 10 eV to 2 keV by using a varied-line-spaced grating. Transitions producing soft X-rays can be detected and accurate MACs are required for use in quantification. This work uses Monte Carlo modeling coupled with multivoltage SXES measurements in an electron probe micro-analyzer (EPMA) to compute MACs for the L2,3-M and Li Kα transitions in a variety of aluminum alloys. Electron depth distribution curves obtained by the software MC X-ray are used in a parametrized fitting equation. The MACs are calculated using a least-squares regression analysis. It is shown that X-ray distribution cross-sections at such low energies need to take into account additional contributions, such as Coster­Kronig transitions, Auger yields, and wave function effects in order to be accurate.

Deciphering the Complex Mineralogy of River Sand Deposits through Clustering and Quantification of Hyperspectral X-Ray Maps.

Alluvial mineral sands rank among the most complex subjects for mineral characterization due to the diverse range of minerals present in the sediments, which may collectively contain a daunting number of elements (>20) in major or minor concentrations (>1 wt%). To comprehensively characterize the phase abundance and chemistry of these complex mineral specimens, a method was developed using hyperspectral x-ray and cathodoluminescence mapping in an electron probe microanalyser (EPMA), coupled with automated cluster analysis and quantitative analysis of clustered x-ray spectra. This method proved successful in identifying and quantifying over 40 phases from mineral sand specimens, including unexpected phases with low modal abundance (<0.1%). The standard-based quantification method measured compositions in agreement with expected stoichiometry, with elemental detection limits in the range of <10­1,000 ppm, depending on phase abundance, and proved reliable even for challenging mineral species, such as the multi-rare earth element (REE) bearing mineral xenotime [(Y,REE)PO4] for which 24 elements were analyzed, including 12 overlapped REEs. The mineral identification procedure was also capable of characterizing mineral groups that exhibit significant compositional variability due to the substitution of multiple elements, such as garnets (Mg, Ca, Fe, Mn, Cr), pyroxenes (Mg, Ca, Fe), and amphiboles (Na, Mg, Ca, Fe, Al).

Soft X-Ray and Cathodoluminescence Examination of a Tanzanian Graphite Deposit.

Hyperspectral soft X-ray emission (SXE) and cathodoluminescence (CL) spectrometry have been used to investigate a carbonaceous-rich geological deposit to understand the crystallinity and morphology of the carbon and the associated quartz. Panchromatic CL maps show both the growth of the quartz and the evidence of recrystallization. A fitted CL map reveals the distribution of Ti4+ within the grains and shows subtle growth zoning, together with radiation halos from 238U decay. The sensitivity of the SXE spectrometer to carbon, together with the anisotropic X-ray emission from highly orientated pyrolytic graphite, has enabled the C Kα peak shape to be used to measure the crystal orientation of individual graphite regions. Mapping has revealed that most grains are predominantly of a single orientation, and a number of graphite grains have been investigated to demonstrate the application of this new SXE technique. A peak fitting approach to analyzing the SXE spectra was developed to project the C Kα 2pz and 2p(x+y) orbital components of the graphite. The shape of these two end-member components is comparable to those produced by electron density of states calculations. The angular sensitivity of the SXE spectrometer has been shown to be comparable to that of electron backscatter diffraction.

Investigation of the Internal Structure of a Modern Seafloor Hydrothermal Chimney With a Combination of EBSD, EPMA, and XRD.

Samples from the sphalerite-dominated zone of a seafloor massive sulfide chimney, the Satanic Mills Chimney of the PACMANUS hydrothermal field, have been investigated to determine the internal macrostructure and microstructure of this zone, the phases present, and the distribution of metals. A combination of electron probe microanalysis, electron backscattered diffraction, and x-ray diffraction has been used. At the macroscale, this zone of the chimney wall is heavily porous and is comprised primarily of sphalerite, enclosing minor chalcopyrite, pyrite, and wurtzite. A Pb­As sulfosalt layer of possible microbial origins is present at the outer edge of the sphalerite matrix, next to a pore. The sphalerite has grown in globules on the order of 300 µm in diameter. At the microscale, the sphalerite features a colloform texture and a duplex-type grain structure consisting of either fine-grain regions in the center surrounded by coarse-grained regions or radiating coarse grains only. Pb- and As-rich bands have been detected in the colloform sphalerite, and growth twins have been observed in both the sphalerite and chalcopyrite crystals. A qualitative description of the growth of a typical globule is given, including nucleation, crystal growth, and solute redistribution.

Blending Human and Machine: Feasibility of Measuring Fatigue Through the Aviation Headset.

OBJECTIVE: To determine viability of drowsiness detection, researchers study the feasibility of photoplethysmogram (PPG) data collection from the geography of the aviation headset, correlating to electrocardiogram (ECG) reference. BACKGROUND: Fatigue has been a probable cause, contributing factor, or a finding in 20% of transportation incidents and accidents studied between January 2001 and December 2012. This operational hazard is particularly troublesome within aviation and airline operations. METHOD: PPG and ECG data were collected synchronously from Federal Aviation Administration (FAA) commercially rated pilots during flight simulation in the window of circadian low (WOCL). Valid PPG and ECG data from 14 participants were analyzed, which yielded approximately 2 hr of data per participant for fatigue-related analysis. RESULTS: The results of the study demonstrate clear trends toward decreased heart rate for both ECG and PPG and suggest progression of drowsiness between four separate periods (T1, T2, T3, and T4) selected during the study; however, the mean heart rate change from T1 to T4 was statistically significant. CONCLUSION: The results suggest that ECG and PPG data can be an important tool to observe conditions where drowsiness or fatigue may add risk to the operation. In addition, the data show high correlation between ECG and PPG data, further suggesting that a simpler PPG sensor, mounted within the geography of the aviation headset, may streamline the operationalization of important physiological data. APPLICATION: Incorporation of PPG sensors and associated signal processing methods into facilitating equipment, such as the aviation headset, may add a layer to operational safety.