Trends in workplace homicides in the U.S., 1994-2021: An end to years of decline.

Workplace and non-workplace homicides in the United States (U.S.) have declined for over 30 years until recently. This study was conducted to address the change in trends for both workplace and non-workplace homicides and to evaluate the homogeneity of the change in workplace homicides by specified categories. Joinpoint and autoregressive models were used to assess trends of U.S. workplace and non-workplace homicides utilizing surveillance data collected by the Bureau of Labor Statistics and the Federal Bureau of Investigation from 1994 through 2021. Both workplace and non-workplace homicides decreased significantly from 1994 through 2014. Workplace homicides showed no significant trend from 2014 through 2021 (p = 0.79), while non-workplace homicides showed a significant average annual increase of 4.1% from 2014 through 2020 (p = 0.0013). The large decreases in the trend of workplace homicides occurring during a criminal act, such as robbery, leveled off and started to increase by the end of the study period (p < 0.0001). Declines in workplace homicides due to shootings also leveled off and started to increase by the end of the study period (p < 0.0001). U.S. workplace and non-workplace homicide rates declined from the 1990s until around 2014. Trends in workplace homicides varied by the types of the homicide committed and by the type of employee that was the victim. Criminal-intent-related events, such as robbery, appear to be the largest contributor to changes in workplace homicides. Researchers and industry leaders could develop and evaluate interventions that further address criminal-intent-related workplace homicides.

Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis.

In mitochondria, the oxidation of nutrients is coupled to ATP synthesis by the generation of a protonmotive force across the mitochondrial inner membrane. In mammalian brown adipose tissue (BAT), uncoupling protein 1 (UCP1, SLC25A7), a member of the SLC25 mitochondrial carrier family, dissipates the protonmotive force by facilitating the return of protons to the mitochondrial matrix. This process short-circuits the mitochondrion, generating heat for non-shivering thermogenesis. Recent cryo-electron microscopy (cryo-EM) structures of human UCP1 have provided new molecular insights into the inhibition and activation of thermogenesis. Here, we discuss these structures, describing how purine nucleotides lock UCP1 in a proton-impermeable conformation and rationalizing potential conformational changes of this carrier in response to fatty acid activators that enable proton leak for thermogenesis.

Structural characterization of fatty acid anions via gas-phase charge inversion using Mg(tri-butyl-terpyridine)2 2+ reagent ions.

RATIONALE: Free fatty acids and lipid classes containing fatty acid esters are major components of lipidome. In the absence of a chemical derivatization step, FA anions do not yield all of the structural information that may be of interest under commonly used collision-induced dissociation (CID) conditions. A line of work that avoids condensed-phase derivatization takes advantage of gas-phase ion/ion chemistry to charge invert FA anions to an ion type that provides the structural information of interest using conventional CID. This work was motivated by the potential for significant improvement in overall efficiency for obtaining FA chain structural information. METHODS: A hybrid triple quadrupole/linear ion-trap tandem mass spectrometer that has been modified to enable the execution of ion/ion reaction experiments was used to evaluate the use of 4,4',4″-tri-tert-butyl-2,2':6',2″-terpyridine (ttb-Terpy) as the ligand in divalent magnesium complexes for charge inversion of FA anions. RESULTS: Mg(ttb-Terpy)2 2+ complexes provide significantly improved efficiency in producing structurally informative products from FA ions relative to Mg(Terpy)2 2+ complexes, as demonstrated for straight-chain FAs, branched-chain FAs, unsaturated FAs, and cyclopropane-containing FAs. It was discovered that most of the structurally informative fragmentation from [FA-H + Mg(ttb-Terpy)]+ results from the loss of a methyl radical from the ligand followed by radical-directed dissociation (RDD), which stands in contrast to the charge-remote fragmentation (CRF) believed to be operative with the [FA-H + Mg(Terpy)]+ ions. CONCLUSIONS: This work demonstrates that a large fraction of product ions from the CID of ions of the form [FA-H + Mg(ttb-Terpy)]+ are derived from RDD of the FA backbone, with a very minor fraction arising from structurally uninformative dissociation channels. This ligand provides an alternative to previously used ligands for the structural characterization of FAs via CRF.

Middle East and North Africa: Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023)This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa we first conducted in 2020 with two additional years of data for the region.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa we first conducted in 2020 with two additional years of data for the region. OBJECTIVE: The objective of this study is to determine whether the Middle East and North Africa region meets the criteria for moving from a pandemic to endemic. In doing so, this study considers pandemic trends, dynamic and genomic surveillance methods, and region-specific historical context for the pandemic. These considerations continue through the World Health Organization (WHO) declaration of the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed of COVID-19 spread was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data from September 4, 2020, to May 12, 2023. RESULTS: The speed of COVID-19 spread for the region had remained below the outbreak threshold for seven continuous months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1- and 7-day persistence coefficients remained statistically significant and positive, the weekly shift parameters suggested the coefficients had most recently turned negative, meaning the clustering effect of new COVID-19 cases became even smaller in the two weeks around the WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed of spread equal to ten became entirely insignificant from October 2022 onward. CONCLUSIONS: The COVID-19 pandemic had far-reaching effects on MENA, impacting healthcare systems, economies, and social well-being. While COVID-19 continues to circulate in the Middle East and North Africa, the rate of transmission remained well below the threshold of an outbreak for over one year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had transitioned to endemic by the time of the WHO declaration.

European Surveillance and History of the COVID-19 Pandemic: Updated Epidemiological Assessment.

BACKGROUND: COVID-19 surveillance plays a crucial role in monitoring the pandemic's progression and comprehending its impact on diverse regions. In this study, we build upon our initial research published in 2020 by incorporating an additional two years of data for Europe. We assess whether COVID-19 had shifted from pandemic to endemic in the region when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. OBJECTIVE: First, we measure whether there was an expansion or contraction in the pandemic in Europe at the time of the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we provide the historical context for the course of the pandemic in Europe in terms of policy and disease burden at the country and region levels. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for four months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were moderate in magnitude (0.404 and 0.547, respectively). The shift parameters for the two weeks around the WHO declaration were small and insignificant, suggesting little change in the clustering effect of cases on future cases at the time. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten became insignificant for the first time in April 2023. CONCLUSIONS: While COVID-19 continues to circulate in Europe, the rate of transmission remained below the threshold of an outbreak for four months ahead of the WHO declaration. The region had previously been in a nearly continuous state of outbreak. The more recent trend suggest COVID-19 was endemic in the region and no longer reached the threshold of the pandemic definition. However, several countries remained in a state of outbreak, and the conclusion that COVID-19 was no longer pandemic in Europe at the time is unclear.

Latin America and the Caribbean: Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023).

BACKGROUND: This study updates the COVID-19 surveillance in Latin America and the Caribbean we first conducted in 2020 with two additional years of data for the region. OBJECTIVE: First, we measure whether there pandemic was expanding or contracting in Latin America and the Caribbean when the World Health Organization (WHO) declared the end of COVID-19 as a public health emergency of international concern on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, with a focus on prevention policies, we provide historical context for the course of the pandemic in the region. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Additionally, we conducted a one-sided t-test for whether regional weekly speed was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data across the period from August 2020 to May 2023. RESULTS: Speed, or the rate of novel COVID-19 transmissions, for the region had remained below the outbreak threshold for six months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1- and 7-day persistence coefficients remained statistically significant for the 120-day period ending on the week of May 5, 2023, the coefficients were relatively modest in magnitude (0.457 and 0.491, respectively). Furthermore, the shift parameters for either of the two most recent weeks around May 5, 2023, did not indicate any change in this clustering effect of cases on future cases. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten became entirely insignificant from January 2023 onward. CONCLUSIONS: While COVID-19 continues to circulate in Latin America and the Caribbean, the rate of transmission had remained well below the threshold of an outbreak for six months ahead of the WHO declaration. Surveillance data suggest COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. However, the region experienced a high COVID-19 disease burden in the early stages of the pandemic, and prevention policies should be an immediate focus in future pandemics. Ahead of vaccination development, these policies can include widespread testing of individuals and an epidemiological task force with a contact-tracing system.

Multi-harmonic near-infrared-ultraviolet dual-comb spectrometer.

Dual-comb spectroscopy in the ultraviolet (UV) and visible would enable broad bandwidth electronic spectroscopy with unprecedented frequency resolution. However, there are significant challenges in generation, detection, and processing of dual-comb data that have restricted its progress in this spectral region. In this work, we leverage robust 1550 nm few-cycle pulses to generate frequency combs in the UV-visible. We combine these combs with a wavelength multiplexed dual-comb spectrometer and simultaneously retrieve 100 MHz comb-mode-resolved spectra over three distinct harmonics at 386, 500, and 760 nm. The experiments highlight the path to continuous dual-comb coverage spanning 200-750 nm, offering extensive access to electronic transitions in atoms, molecules, and solids.

Venous thromboembolism chemical prophylaxis after skull base surgery.

PURPOSE: There is no guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using pharmacological agents (chemoprophylaxis) in patients undergoing skull base surgery. The aim of this study was to compare VTE and intracranial haematoma rates after skull base surgery in patients treated with/without chemoprophylaxis. METHODS: Review of prospective quaternary centre database including adults undergoing first-time skull base surgery (2009-2020). VTE was defined as deep vein thrombosis (DVT) and pulmonary embolism (PE) within 6 months of surgery. Multivariate logistic regression was used to determine factors predictive of postoperative intracranial haematoma/VTE. Propensity score matching (PSM) was used in group comparisons. RESULTS: One thousand five hundred fifty-one patients were included with a median age of 52 years (range 16-89 years) and female predominance (62%). Postoperative chemoprophylaxis was used in 81% of patients at a median of 1 day postoperatively. There were 12 VTE events (1.2%), and the use of chemoprophylaxis did not negate the risk of VTE entirely (p > 0.99) and was highest on/after postoperative day 6 (9/12 VTE events). There were 18 intracranial haematomas (0.8%), and after PSM, chemoprophylaxis did not significantly increase the risk of an intracranial haematoma (p > 0.99). Patients administered chemoprophylaxis from postoperative days 1 and 2 had similar rates of intracranial haematomas (p = 0.60) and VTE (p = 0.60), affirmed in PSM. CONCLUSION: Postoperative chemoprophylaxis represents a relatively safe strategy in patients undergoing skull base surgery. We advocate a personalised approach to chemoprophylaxis and recommend it on postoperative days 1 or 2 when indicated.

Adverse Pregnancy Outcomes and Pharyngeal Flow Limitation during Sleep: Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b).

RATIONALE: Pharyngeal flow limitation during pregnancy may be a risk factor for adverse pregnancy outcomes but was previously challenging to quantify. OBJECTIVE: To determine whether a novel objective measure of flow limitation identifies an increased risk of preeclampsia (primary outcome) and other adverse outcomes in a prospective cohort: Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be. METHODS: Flow limitation severity scores (0%=fully obstructed, 100%=open airway)- quantified from breath-by-breath airflow shape-were obtained from home sleep tests during early (6-15 weeks) and mid (22-31 weeks) pregnancy. Multivariable logistic regression quantified associations between flow limitation (median overnight severity, both time-points averaged) and preeclampsia, adjusting for maternal age, body mass index (BMI), race, ethnicity, chronic hypertension, and flow limitation during wakefulness. Secondary outcomes were hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), and infant birthweight. RESULTS: Of 1939 participants with flow limitation data at both time-points (age: 27.0±5.4 yr [mean±sd], BMI: 27.7±6.1 kg·m-2), 5.8% developed preeclampsia, 12.7% developed HDP, and 4.5% developed GDM. Greater flow limitation was associated with increased preeclampsia risk: adjusted Odds Ratio (OR) 2.49, 95% Confidence Interval [1.69, 3.69], per 2SD increase in severity. Findings persisted in women without sleep apnea (apnea-hypopnea index <5 events·hr-1). Flow limitation was associated with HDP (OR: 1.77 [1.33, 2.38]) and reduced infant birthweight (83.7 [31.8, 135.6] g), but not GDM. CONCLUSIONS: Greater flow limitation is associated with increased risk of preeclampsia, HDP, and lower infant birthweight. Flow limitation may provide an early target for mitigating the consequences of sleep disordered breathing during pregnancy.

Adiponectin overexpression improves metabolic abnormalities caused by acid ceramidase deficiency but does not prolong lifespan in a mouse model of Farber Disease.

Farber Disease is a debilitating and lethal childhood disease of ceramide accumulation caused by acid ceramidase deficiency. The potent induction of a ligand-gated neutral ceramidase activity promoted by adiponectin may provide sufficient lowering of ceramides to allow for the treatment of Farber Disease. In vitro, adiponectin or adiponectin receptor agonist treatments lowered total ceramide concentrations in human fibroblasts from a patient with Farber Disease. However, adiponectin overexpression in a Farber Disease mouse model did not improve lifespan or immune infiltration. Intriguingly, mice heterozygous for the Farber Disease mutation were more prone to glucose intolerance and insulin resistance when fed a high-fat diet, and adiponectin overexpression protected from these metabolic perturbations. These studies suggest that adiponectin evokes a ceramidase activity that is not reliant on the functional expression of acid ceramidase, but indicates that additional strategies are required to ameliorate outcomes of Farber Disease.

Mediation of antitumor activity by AZD4820 oncolytic vaccinia virus encoding IL-12.

Oncolytic viruses are engineered to selectively kill tumor cells and have demonstrated promising results in early-phase clinical trials. To further modulate the innate and adaptive immune system, we generated AZD4820, a vaccinia virus engineered to express interleukin-12 (IL-12), a potent cytokine involved in the activation of natural killer (NK) and T cells and the reprogramming of the tumor immune microenvironment. Testing in cultured human tumor cell lines demonstrated broad in vitro oncolytic activity and IL-12 transgene expression. A surrogate virus expressing murine IL-12 demonstrated antitumor activity in both MC38 and CT26 mouse syngeneic tumor models that responded poorly to immune checkpoint inhibition. In both models, AZD4820 significantly upregulated interferon-gamma (IFN-γ) relative to control mice treated with oncolytic vaccinia virus (VACV)-luciferase. In the CT26 study, 6 of 10 mice had a complete response after treatment with AZD4820 murine surrogate, whereas control VACV-luciferase-treated mice had 0 of 10 complete responders. AZD4820 treatment combined with anti-PD-L1 blocking antibody augmented tumor-specific T cell immunity relative to monotherapies. These findings suggest that vaccinia virus delivery of IL-12, combined with immune checkpoint blockade, elicits antitumor immunity in tumors that respond poorly to immune checkpoint inhibitors.

Finding the right balance: The enduring role of florigens during cereal inflorescence development and their influence on fertility.

Flowering is a vital process in a plant's lifecycle and variation for flowering-time has helped cereals adapt to diverse environments. Much cereal research has focused on understanding how flowering signals, or florigens, regulate the floral transition and timing of ear emergence. However, flowering genes also perform an enduring role during inflorescence development, with genotypes that elicit a weaker flowering signal producing more elaborately branched inflorescences with extra floret-bearing spikelets. While this outcome indicates that variable expression of flowering genes could boost yield potential, further analysis has shown that dampened florigen levels can compromise fertility, negating the benefit of extra grain-producing sites. Here, we discuss ways that florigens contribute to early and late inflorescence development, including their influence on branch/spikelet architecture and fertility. We propose that a deeper understanding of the role for florigens during inflorescence development could be used to balance the effects of florigens throughout flowering to improve productivity.

Ion parking in native mass spectrometry.

A forced, damped harmonic oscillator model for gas-phase ion parking using single-frequency resonance excitation is described and applied to high-mass ions of relevance to native mass spectrometry. Experimental data are provided to illustrate key findings revealed by the modelling. These include: (i) ion secular frequency spacings between adjacent charge states of a given protein are essentially constant and decrease with the mass of the protein (ii) the mechanism for ion parking of high mass ions is the separation of the ion clouds of the oppositely-charged ions with much less influence from an increase in the relative ion velocity due to resonance excitation, (iii) the size of the parked ion cloud ultimately limits ion parking at high m/z ratio, and (iv) the extent of ion parking of off-target ions is highly sensitive to the bath gas pressure in the ion trap. The model is applied to ions of 17 kDa, 467 kDa, and 2 MDa while experimental data are also provided for ions of horse skeletal muscle myoglobin (≈17 kDa) and ß-galactosidase (≈467 kDa). The model predicts and data show that it is possible to effect ion parking on a 17 kDa protein to the 1+ charge state under trapping conditions that are readily accessible with commercially available ion traps. It is also possible to park ß-galactosidase efficiently to a roughly equivalent m/z ratio (i.e., the 26+ charge state) under the same trapping conditions. However, as charge states decrease, analyte ion cloud sizes become too large to allow for efficient ion trapping. The model allows for a semi-quantitative prediction of ion trapping performance as a function of ion trapping, resonance excitation, and pressure conditions.

A meta-analysis of the incidence of acne vulgaris in patients treated with GLP-1 agonists.

Background: With the emerging popularity of GLP-1 receptor agonists, patients are noticing acne vulgaris side effects that are seemingly related to the concurrent treatment with the drug. Due to the correspondence between these drugs' relatively recent emergence in the U.S. market and their high demand, it is important to investigate what is currently known in the literature so that patients can be properly informed. Objective: The aim of this study is to investigate the relationship, or lack thereof, between glucagon like peptide 1 (GLP-1) receptor agonist usage and acne-related side effects in patients. Methods: A web-based analysis of 6 GLP-1 receptor agonists (3 with a once-weekly dosing schedule, and 3 with a once-daily dosing schedule) was conducted on PubMed online database. Boolean criteria were used to narrow the search. Included in the meta-analysis were 45 research articles that fulfilled the search criteria. Results: The results of the search showed that from the following long-acting GLP-1 receptor agonists, dulaglutide, exenatide extended release, and semaglutide (Wegovy), no conclusive acne side effects were reported. In addition, the results also showed that from the following short-acting GLP-1 receptor agonists, liraglutide, lixisenatide, and semaglutide (Rybelsus), no conclusive acne side effects were reported. Limitations: Limitations of this study include a limited amount of literature regarding the relationship between GLP-1 agonists and acne vulgaris. Conclusion: It is unlikely that GLP-1 agonists themselves are directly responsible for the acne that some patients may develop during treatment. Rather, it is more probable that the weight loss yielded by treatment with these drugs may induce intrinsic physiologic and hormonal changes that induce or exacerbate acne vulgaris in such patients.

An Online Learning Experience Simulating Video Telehealth with Older Adults: Student Perceptions.

Older adults are an underserved population with a broad-spectrum of care needs due to multi-morbidity, including increasing rates of mental health conditions. Though a prime target for tele-behavioral health due to access barriers, older adults face a persistent digital divide that necessitates clinician training and education to ensure interprofessional tele-behavioral health is tailored to their needs. This paper presents findings from a simulation learning program designed to teach students about the role of video telehealth with populations with diverse needs. Occupational therapy (OT) students enrolled in a Master's program between 2017 and 2018 conducted a simulated video telehealth session geared for an older adult. Sessions were recorded and annotated by students, who then provided feedback on their experience of the simulation via reflective essays (N = 27). Essays were analyzed using conventional content analysis with themes revealing the benefits of simulation in providing students with an opportunity to experience the often unpredictable nature of video telehealth. Themes also revealed perceived limitations of video and the negative impact of age-related conditions and age itself on older adults' ability to engage in video, reflecting ageist stereotyping and bias as potential barriers to novice practitioners' integration of video telehealth with older adults. Simulation provides students an opportunity to engage in active learning and problem-solving in the moment, fostering students' development of clinical reasoning while promoting reflective practice. Findings reveal the importance of supporting students' recognition of biased attitudes to ensure equitable application of tele-behavioral health care, especially to populations with complex needs.

User Experience of Access to Sexual Assault Nurse Examiner and Emergency Contraception in Emergency Departments in the United States: A National Survey.

Background: Despite the prevalence of sexual assault presentations to emergency departments (ED) in the United States, current access to sexual assault nurse examiners (SANE) and emergency contraception (EC) in EDs is unknown. Methods: In this study we employed a "secret shopper," cross-sectional telephonic survey. A team attempted phone contact with a representative sample of EDs and asked respondents about the availability of SANEs and EC in their ED. Reported availability was correlated with variables including region, urban/rural status, hospital size, faith affiliation, academic affiliation, and existence of legislative requirements to offer EC. Results: Over a two-month period in 2019, 1,046 calls to hospitals were attempted and 960 were completed (91.7% response rate). Of the 4,360 eligible hospitals listed in a federal database, 960 (22.0%) were contacted. Access to SANEs and EC were reported to be available in 48.9% (95% confidence interval [CI] 45.5-52.0) and 42.5% (95% CI 39.4-45.7) of hospitals, respectively. Access to EC was positively correlated with SANE availability. The EDs reporting SANE and EC availability were more likely to be large, rural, and affiliated with an academic institution. Those reporting access to EC were more likely to be in the Northeast and in states with legislative requirements to offer EC. Conclusion: Our results suggest that perceived access to sexual assault services and emergency contraception in EDs in the United States remains poor with regional and legislative disparities. Results suggest disparities in perceived access to EC and SANE in the ED, which have implications for improving ED practices regarding care of sexual assault victims.

Gradients in embolism resistance within stems driven by secondary growth in herbs.

The stems of some herbaceous species can undergo basal secondary growth, leading to a continuum in the degree of woodiness along the stem. Whether the formation of secondary growth in the stem base results in differences in embolism resistance between the base and the upper portions of stems is unknown. We assessed the embolism resistance of leaves and the basal and upper portions of stems simultaneously within the same individuals of two divergent herbaceous species that undergo secondary growth in the mature stem bases. The species were Solanum lycopersicum (tomato) and Senecio minimus (fireweed). Basal stem in mature plants of both species displayed advanced secondary growth and greater resistance to embolism than the upper stem. This also resulted in significant vulnerability segmentation between the basal stem and the leaves in both species. Greater embolism resistance in the woodier stem base was found alongside decreases in the pith-to-xylem ratio, increases in the proportion of secondary xylem, and increases in lignin content. We show that there can be considerable variation in embolism resistance across the stem in herbs and that this variation is linked to the degree of secondary growth present. A gradient in embolism resistance across the stem in herbaceous plants could be an adaptation to ensure reproduction or basal resprouting during episodes of drought late in the lifecycle.

PET Quantification of [18F]VAT in Human Brain and Its Test-Retest Reproducibility and Age Dependence.

Molecular imaging of brain vesicular acetylcholine transporter provides a biomarker to explore cholinergic systems in humans. We aimed to characterize the distribution of, and optimize methods to quantify, the vesicular acetylcholine transporter-specific tracer (-)-(1-(8-(2-[18F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([18F]VAT) in the brain using PET. Methods: Fifty-two healthy participants aged 21-97 y had brain PET with [18F]VAT. [3H]VAT autoradiography identified brain areas devoid of specific binding in cortical white matter. PET image-based white matter reference region size, model start time, and duration were optimized for calculations of Logan nondisplaceable binding potential (BPND). Ten participants had 2 scans to determine test-retest variability. Finally, we analyzed age-dependent differences in participants. Results: [18F]VAT was widely distributed in the brain, with high striatal, thalamic, amygdala, hippocampal, cerebellar vermis, and regionally specific uptake in the cerebral cortex. [3H]VAT autoradiography-specific binding and PET [18F]VAT uptake were low in white matter. [18F]VAT SUVs in the white matter reference region correlated with age, requiring stringent erosion parameters. Logan BPND estimates stabilized using at least 40 min of data starting 25 min after injection. Test-retest variability had excellent reproducibility and reliability in repeat BPND calculations for 10 participants (putamen, 6.8%; r > 0.93). We observed age-dependent decreases in the caudate and putamen (multiple comparisons corrected) and in numerous cortical regions. Finally, we provide power tables to indicate potential mean differences that can be detected between 2 groups of participants. Conclusion: These results validate a reference region for BPND calculations and demonstrate the viability, reproducibility, and utility of using the [18F]VAT tracer in humans to quantify cholinergic pathways.

New Oldowan locality Sare-Abururu (ca. 1.7 Ma) provides evidence of diverse hominin behaviors on the Homa Peninsula, Kenya.

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3-2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition.