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Abstract: Since the late Miocene, plants using the C4 photosynthetic pathway have increased to become major components of many tropical and subtropical ecosystems. However, the drivers for this expansion remain under debate, in part because of the varied histories of C4 vegetation on different continents. Australia hosts the highest dominance of C4 vegetation of all continents, but little is known about the history of C4 vegetation there. Carbon isotope ratios of plant waxes from scientific ocean drilling sediments off north‐western Australia reveal the onset of Australian C4 expansion at ~3.5 Ma, later than in many other regions. Pollen analysis from the same sediments reveals increasingly open C3‐dominated biomes preceding the shift to open C4‐dominated biomes by several million years. We hypothesize that the development of a summer monsoon climate beginning in the late Pliocene promoted a highly seasonal precipitation regime favorable to the expansion of C4 vegetation. [ABSTRACT FROM AUTHOR]

The Msh2-Msh3 mismatch repair (MMR) complex in Saccharomyces cerevisiae recognizes and directs repair of insertion/deletion loops (IDLs) up to ∼17 nucleotides. Msh2-Msh3 also recognizes and binds distinct looped and branched DNA structures with varying affinities, thereby contributing to genome stability outside post-replicative MMR through homologous recombination, double-strand break repair (DSBR) and the DNA damage response. In contrast, Msh2-Msh3 promotes genome instability through trinucleotide repeat (TNR) expansions, presumably by binding structures that form from single-stranded (ss) TNR sequences. We previously demonstrated that Msh2-Msh3 binding to 5' ssDNA flap structures interfered with Rad27 (Fen1 in humans)-mediated Okazaki fragment maturation (OFM) in vitro. Here we demonstrate that elevated Msh2-Msh3 levels interfere with DNA replication and base excision repair in vivo. Elevated Msh2-Msh3 also induced a cell cycle arrest that was dependent on RAD9 and ELG1 and led to PCNA modification. These phenotypes also required Msh2-Msh3 ATPase activity and downstream MMR proteins, indicating an active mechanism that is not simply a result of Msh2-Msh3 DNA-binding activity. This study provides new mechanistic details regarding how excess Msh2-Msh3 can disrupt DNA replication and repair and highlights the role of Msh2-Msh3 protein abundance in Msh2-Msh3-mediated genomic instability., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Firefighters are routinely exposed to loud noise that put them at risk for hearing loss. A reliable and valid measure to assess firefighters' hearing function is important. This study aims to test the reliability and validity of the modified Amsterdam Inventory for Auditory Disability and Handicap ((m)AIADH) in firefighters., Method: A cross-sectional study was conducted using a convenience sample of 239 career firefighters from six partnered fire departments in Central Texas and Northern California. The internal consistency, convergent and criterion validity, and the ability to discriminate groups by measured hearing, perceived hearing, and a combination of measured and perceived hearing, were examined using the total score and score for each of the five subscales of the (m)AIADH., Results: The study participants were primarily men (93%). Satisfactory internal consistency was revealed for the (m)AIADH with Cronbach's alpha above 0.80 for all five subscales. Criterion analysis presented a moderate correlation between the (m)AIADH and the average of hearing threshold at high frequencies (4, 6, and 8 kHz). For convergent validity, the (m)AIADH was moderately to highly related with perceived hearing. There were statistically significant differences in the total (m)AIADH score and the five subscales for measured hearing thresholds except for "intelligibility in quiet." The (m)AIADH also showed a discriminative ability to distinguish between the group with good perceived hearing and the group with bad perceived hearing., Conclusion: The (m)AIADH is a reliable and valid measure to assess various dimensions of hearing function among firefighters., (© 2023 Wiley Periodicals LLC.)

Clinical disease caused by infection with Listeria monocytogenes is rare in adult horses, and there is a paucity of ante-mortem clinicopathologic changes for this species reported in the literature. Confirmatory diagnosis is difficult and often requires post-mortem sampling of the brainstem. This report details a case of meningoencephalitis caused by Listeria monocytogenes in an adult American quarter horse gelding presenting with central neurologic signs. Pre-mortem analysis of the cerebrospinal fluid revealed a mononuclear, primarily lymphocytic, pleocytosis, which is a reported finding in other species with listeriosis. Post-mortem histopathologic changes of the brainstem were characteristic of listeriosis, and infection was confirmed with immunohistochemical labeling and bacterial culture. Key clinical message: Listeriosis should be included as a differential diagnosis in neurologic horses with mononuclear pleocytosis identified on cerebrospinal fluid analysis., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Purpose: The original effort-reward imbalance (ERI) questionnaire has been widely used as a measure of occupational stress. The need for brief measurement of psychosocial stress at work has risen. This study examined the psychometric properties of a 16-item short form ERI (S-ERI) questionnaire., Methods: A cross-sectional study was conducted with a convenience sample of 247 career firefighters in the United States. An internet-based survey contained the S-ERI questionnaire, and assessed perceived health, demographics, and work characteristics. Internal consistency was tested by item-total correlation and Cronbach's α coefficients. Factorial validity was assessed by confirmatory factor analysis (CFA), and criterion validity was examined by testing the S-ERI's association with perceived health, controlling for other factors., Results: The study participants were primarily young and mid-aged White males (mean age = 42 years, 75% White non-Hispanic, 93% males). The S-ERI questionnaire showed satisfactory internal consistency, with Cronbach α coefficients above 0.80 for all three scales: effort 0.82, reward 0.83, and overcommitment 0.81. CFA showed all the S-ERI components had a good fit (goodness-of-fit index = 0.99, comparative fit index = 0.92, root mean square error of approximation = 0.06). In terms of criterion validity, significantly increased odds ratios (ORs) for perceived health (those indicating they were less healthy) were found in firefighters in the lowest tertile of reward (OR = 7.06, 95% confidence interval [CI]: 2.86-17.43), and highest tertile of overcommitment (OR = 2.29, 95% CI: 1.00-5.22), after controlling for other factors., Conclusion: The S-ERI questionnaire is a reliable and valid measure to assess occupational stress. We recommend the use of S-ERI as a measure of occupational stress when initiating efforts to improve firefighters' wellness., (© 2022 Wiley Periodicals LLC.)

Intravascular catheters are widely used among hospitals; however, their failure rates are high, up to 50%, when secured by traditional techniques, such as tape and gauze. The use of catheter securement cyanoacrylate adhesives provides a unique approach to the issues surrounding the use of traditional securement techniques for vascular access devices by providing significant securement strength, barrier properties, antibacterial properties, hemostatic properties, and flexibility. The purpose of this research was to perform a thorough and systematic review of the current literature existing regarding the use of cyanoacrylate adhesive for the care and maintenance of vascular access devices., (Copyright © 2022 Infusion Nurses Society.)

Background: With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests., Methods: We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients., Results: In a cohort of 75 991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July 2020, 7335 of whom were positive by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%])., Conclusions: Although molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Despite having close contact with the general public, members of the San Francisco Fire Department (SFFD) reported relatively few cases of COVID-19 during the first half of 2020. Our objective was to explore evidence for prior undetected infections by conducting a seroprevalence survey, and to document both risk and protective factors for prior COVID-19 infection., Methods: This cross-sectional study assessed workplace practices and exposures of SFFD personnel during the first 6 months of 2020 via questionnaire and documented prior COVID-19 infections by serologic antibody testing using an orthogonal testing protocol., Results: Of 1231 participating emergency responders, three (0.25%) had confirmed positive COVID-19 antibody results., Conclusions: Safe workplace practices, community public health intervention, and low community infection rates appear to have been protective factors for emergency responders in San Francisco during our study period., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Background: We experienced a high incidence of jejunal tube (JEJ) displacement in children who underwent percutaneous endoscopic transgastric jejunostomy (PEGJ), ever since the introduction of ENFit connector (2017)., Methods: Two interventions were introduced in 2018 - fixative suture to PEGJ ENFit connector, and conversion to balloon transgastric-jejunal feeding device (Balloon GJ) whenever possible. Children receiving PEGJ and Balloon GJ in 2.8 years were categorized into 3 eras: 2016 (pre-ENFit), 2017 (ENFit) and 2018 (interventional), for comparison of complications and sequelae. Kaplan-Meier survival curves with log-rank test (P < 0.05) were applied., Results: 100 children underwent 323 JEJ insertions - PEGJ (n = 237), Balloon GJ (n = 86). Complications occurred in 188 JEJs (58%), more frequently with PEGJ than Balloon GJ (69% vs. 29%, P < 0.0005). PEGJ had higher complication/1000-tube-days (6 vs. 0, P < 0.0005). In 2018, complication rate reduced from 76% to 30% (P < 0.0005) owing to effectiveness of PEGJ connector suture application (P = 0.019), and increased utilization of Balloon GJ (16% to 44%, P = 0.005). Balloon GJ showed better JEJ survival (P = 0.019), less morbidity (emergency attendance, X-ray) and greater cost-effectiveness than PEGJ., Conclusions: Balloon GJ had better overall outcomes than PEGJ. Suture application to connector successfully reduced JEJ internal displacement in PEGJ; however, conversion to Balloon GJ should be strongly considered., Level of Evidence: II., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a surge in clinical trials evaluating investigational and approved drugs. Retrospective analysis of drugs taken by COVID-19 inpatients provides key information on drugs associated with better or worse outcomes., Methods: We conducted a retrospective cohort study of 10 741 patients testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 3 days of admission to compare risk of 30-day all-cause mortality in patients receiving ondansetron using multivariate Cox proportional hazard models. All-cause mortality, length of hospital stay, adverse events such as ischemic cerebral infarction, and subsequent positive COVID-19 tests were measured., Results: Administration of ≥8 mg of ondansetron within 48 hours of admission was correlated with an adjusted hazard ratio for 30-day all-cause mortality of 0.55 (95% CI, 0.42-0.70; P  < .001) and 0.52 (95% CI, 0.31-0.87; P  = .012) for all and intensive care unit-admitted patients, respectively. Decreased lengths of stay (9.2 vs 11.6; P  < .001), frequencies of subsequent positive SARS-CoV-2 tests (53.6% vs 75.0%; P  = .01), and long-term risks of ischemic cerebral ischemia (3.2% vs 6.1%; P  < .001) were also noted., Conclusions: If confirmed by prospective clinical trials, our results suggest that ondansetron, a safe, widely available drug, could be used to decrease morbidity and mortality in at-risk populations., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective. To develop a valid and reliable academic resilience scale for use in the didactic portion of the Doctor of Pharmacy curriculum to identify those pharmacy students who have greater capacity to overcome academic adversity. Methods. A cross-sectional survey was conducted among first-year, second-year, and third-year pharmacy students to assess psychometric properties of a 30-item adapted academic resilience scale. Data were also collected using the Short Grit Scale (Grit-S). Demographic characteristics were collected from student records. Exploratory factor analysis was applied to determine the number of underlying factors responsible for data covariation. Principal components analysis was used as the extraction method. Varimax rotation method was used, and the Cronbach alpha was estimated. Validity testing was conducted by calculating Pearson's r correlations between the adapted academic resilience scale and Grit-S. Results. The survey response rate was 84%. The final version of the scale, the Academic Pharmacy Resilience Scale (APRS-16), had four subscales and 16 items (14 items failed to load on any of the factors and were deleted). The Cronbach alpha was .84, indicating strong internal consistency. The APRS-16 and its subscales were significantly correlated to the Grit-S and its subscales, providing evidence of effective convergent validity. Conclusion. Evidence supports the reliability and validity of the APRS-16 as a measure of academic resilience in pharmacy students. Future studies should use the APRS-16 to investigate the relationship between academic resilience and performance outcomes among pharmacy students.

Objective: The purpose of this study is to introduce a wound closure testing method that reproduces a pulling or stretching force, leading to more accurate supporting data for clinicians to select the proper product when closing a low- or high-tension incision in conjunction with deep dermal sutures., Materials and Methods: Incisions were made in the center of 70 prepared porcine skin samples. They were cleaned with isopropanol and wiped dry before applying the adhesive, as per each respective manufacturer's instructions. A tensile tester was used to pull the incisions apart and record each wound closure maximum disruption force. A paired t test assuming unequal variances was performed on the data., Results: This new wound closure test method was determined to be more advantageous when compared with previous methods in terms of approximation incision, approximation of clinical scenario, approximation directional force experienced by incision, number of steps, sample preparation time, and equipment needed. One specific 2-octyl cyanoacrylate topical skin adhesive product was revealed to have statistically significantly higher wound closure strength than most of the investigated adhesives. That topical skin adhesive exhibited a higher mean strength than all other cyanoacrylate tissue adhesives tested in this study., Conclusions: The study indicates this wound closure test has the potential to be an ideal testing method for predicting the strength of a wound-sealing adhesive subjected to a pulling or stretching force. The topical skin adhesive that demonstrated the highest mean strength of the 7 cyanoacrylate adhesive products tested potentially could be the optimal wound closure device for low- or high-tension incisions in conjunction with deep dermal sutures.

In the present report, we carried out clinical-scale editing in adult mobilized CD34+ hematopoietic stem and progenitor cells (HSPCs) using zinc-finger nuclease-mediated disruption of BCL11a to upregulate the expression of γ-globin (fetal hemoglobin). In these cells, disruption of the erythroid-specific enhancer of the BCL11A gene increased endogenous γ-globin expression to levels that reached or exceeded those observed following knockout of the BCL11A coding region without negatively affecting survival or in vivo long-term proliferation of edited HSPCs and other lineages. In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with β-thalassemia major resulted in a readily detectable γ-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. Furthermore, we documented that both normal and β-thalassemia HSPCs not only can be efficiently expanded ex vivo after editing but can also be successfully edited post-expansion, resulting in enhanced early in vivo engraftment compared with unexpanded cells. Overall, this work highlights a novel and effective treatment strategy for correcting the β-thalassemia phenotype by genome editing.

We introduce a Schelling model in which people are modelled as agents following simple behavioural rules which dictate their tolerance to others, their corresponding preference for particular locations, and in turn their movement through a geographic or social space. Our innovation over previous work is to allow agents to adapt their tolerance to others in response to their local environment, in line with contemporary theories from social psychology. We show that adaptive tolerance leads to a polarization in tolerance levels, with distinct modes at either extreme of the distribution. Moreover, agents self-organize into communities of like-tolerance, just as they congregate with those of same colour. Our results are robust not only to variations in free parameters, but also experimental treatments in which migrants are dynamically introduced into the native population. We argue that this model provides one possible parsimonious explanation of the political landscape circa 2016.

Poor insight in schizophrenia is prevalent across cultures and phases of illness. In this review, we examine the recent research on the relationship of insight with behavior, mood and perceived quality of life, on its complex roots, and on the effects of existing and emerging treatments. This research indicates that poor insight predicts poorer treatment adherence and therapeutic alliance, higher symptom severity and more impaired community function, while good insight predicts a higher frequency of depression and demoralization, especially when coupled with stigma and social disadvantage. This research also suggests that poor insight may arise in response to biological, experiential, neuropsychological, social-cognitive, metacognitive and socio-political factors. Studies of the effects of existing and developing treatments indicate that they may influence insight. In the context of earlier research and historical models, these findings support an integrative model of poor insight. This model suggests that insight requires the integration of information about changes in internal states, external circumstances, others' perspectives and life trajectory as well as the multifaceted consequences and causes of each of those changes. One implication is that treatments should, beyond providing education, seek to assist persons with schizophrenia to integrate the broad range of complex and potentially deeply painful experiences which are associated with mental illness into their own personally meaningful, coherent and adaptive picture., (© 2018 World Psychiatric Association.)

Transplantation of small cord blood (CB) units, or of autologous ex vivo-genetically modified adult hematopoietic stem cells (HSC), face the common challenge of suboptimal HSC doses for infusion and impaired engraftment of the transplanted cells. Ex vivo expansion of HSCs, using either cell-based coculture approaches or especially small molecules have been successfully tested mainly in CB and in prolonged cultures. Here, we explored whether innovative combinations of small molecules can sufficiently, after short culture, expand adult HSCs while retaining their functionality in vivo. We found that 5-day cultured cells, in the presence of the small molecule combinations tested, achieved higher engraftment levels in NSG mice than both their uncultured and their cytokine only-cultured counterparts. Surprisingly, the engraftment levels were neither concordant to the numbers of phenotypically similar HSCs expanded under different small molecule combinations, nor explained by their distinct companion cells present. Transcriptomic comparative analysis of sorted, phenotypically similar, ex vivo generated HSCs transplanted in equal numbers, suggested that HSCs generated under expansion conditions that maintain low expression of the Rap1/Ras/PI3K-AKT pathway exhibit a superior functional profile in vivo. Stem Cells Translational Medicine 2017;6:1852-1858., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The Austrian psychiatrist Theodor Meynert's anatomical theories of the brain and nerves are laden with metaphorical imagery, ranging from the colonies of empire to the tentacles of jellyfish. This paper analyses among Meynert's earliest works a different set of less obvious metaphors, namely, the fibres, threads, branches and paths used to elaborate the brain's interior. I argue that these metaphors of material, or what the philosopher Gaston Bachelard called 'material images', helped Meynert not only to imaginatively extend the tracts of fibrous tissue inside the brain but to insinuate their function as pathways co-extensive with the mind. Above all, with reference to Bachelard's study of the material imagination, I argue that Meynert helped entrench the historical intuition that the mind, whatever it was, consisted of some interiority - one which came to be increasingly articulated through the fibrous confines of the brain.

The purpose of this study was to determine the prevalence and characteristics of tinnitus and assess the relationship between tinnitus and hearing loss among firefighters and operating engineers, who are exposed to noise on-the-job. The study analyzed existing data from two different populations (154 firefighters and 769 operating engineers) who completed a survey and audiometric tests as part of a hearing loss prevention intervention study. Approximately 40% of both groups reported tinnitus; 34% of firefighters and 59% of operating engineers showed hearing loss at noise-sensitive frequencies (4 kHz and 6 kHz). Firefighters with high frequency hearing loss (odds ratio [OR] = 2.31; 95% confidence interval [CI] = [1.05, 5.11]) and those with perceived impaired hearing status (OR = 3.53; 95% CI = [1.27, 9.80]) were significantly more likely to report tinnitus. Similarly, operating engineers who had hearing loss at both low (OR = 2.10; 95% CI = [1.40, 3.15]) and high frequencies (OR = 2.00; 95% CI = [1.37, 2.90]), and perceived impaired hearing status (OR = 2.17; 95% CI = [1.55, 3.05]) were twice as likely to report tinnitus. This study demonstrated that tinnitus is a considerable problem for noise-exposed workers. Workers with hearing loss demonstrated significantly higher rates of tinnitus. Comprehensive workplace hearing conservation programs should include tinnitus management for noise-exposed workers, along with other key elements such as noise control and hearing protection., (© 2016 The Author(s).)

Organisms can adapt to variable environments by using environmental cues to modulate developmental gene expression. In principle, maternal influences can adaptively adjust offspring phenotype when early life and adult environments match, but they may be maladaptive when future environments are not predictable. One of the best-studied 'maternal effects' is through modification of the offspring's hypothalamic-pituitary-adrenal (HPA) axis, the neuroendocrine system that controls responses to stress. In addition to the direct transfer of glucocorticoids from mother to offspring, offspring HPA function and other phenotypes can also be affected by epigenetic modifications like DNA methylation of the glucocorticoid receptor promoter. Here we examine how among-year variation in rainfall is related to DNA methylation during development and fitness in adulthood in the superb starling (Lamprotornis superbus), which lives in a climatically unpredictable environment where early life and adult environments are unlikely to match. We found that DNA methylation in the putative promoter of the glucocorticoid receptor gene is reduced in chicks - particularly in males - born following drier prebreeding periods. Additionally, DNA methylation is lower in males that become breeders than those that never breed. However, there is no relationship in females between DNA methylation and the likelihood of dispersing from the natal group to breed elsewhere. These results suggest that early life conditions may positively affect fitness in a sex-specific manner through chemical modification of an HPA-associated gene. This study is the first to show that epigenetic modifications during early life may influence the fitness of free-living organisms adapted to unpredictable environments., (© 2015 John Wiley & Sons Ltd.)

In recent U.S. military experience, widespread exposure to improvised explosive devices has been implicated in noticeable changes in the incidence of brain injuries inversely related to reduced mortality--thought to be the unintended consequence of increase in exposure to blast wave effects--secondary to improved vital organ protection, improved personal protective equipment. Subsequently, there is a growing need for the development and fielding of fully integrated sensor systems capable of both capturing dynamic effects (i.e., "blast") on the battlefield--providing critical information for researchers, while providing value to the medical community and leaders--for development of pre-emptive measures and policies. Obtaining accurate and useful data remains a significant challenge with a need for sensors which feed systems that provide accurate interpretation of dynamic events and lend to an enhanced understanding of their significance to the individual. This article describes lessons learned from a data analysis perspective of a collaborative effort led by a team formed at Georgia Tech Research Institute to develop a "sensor agnostic" system that demonstrates full integration across variant platforms/systems. The system is designed to allow digital and analog time/frequency data synchronization and analysis, which facilitated the development of complex multimodal modeling/algorithms., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)

Spurned by the increasing concern and consciousness of traumatic brain injuries in deployed U.S. service members, the U.S. Army Rapid Equipping Force sought help from the Georgia Tech Research Institute to rapidly develop and deploy a system capable of gathering relevant soldier-centric data-the Integrated Blast Effects Sensor Suite. To meet aggressive program milestones and requirements, Georgia Tech Research Institute engaged in rapid systems engineering efforts focused on leveraging iterative development and test methodologies. Ultimately, an integrated system of systems composed of vehicle systems, soldier-worn headset and torso systems, and data retrieval systems was deployed to troops in Afghanistan for an operational assessment. The Integrated Blast Effects Sensor Suite development process and parallel efforts investigating injury dosimetry methodologies have yielded unique findings and lessons learned, which should be incorporated into future evolutions of similar systems., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)