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Objectives Caregivers of adult phase 1 oncology trial patients experience high levels of distress and face barriers to in-person supportive care. The Phase 1 Caregiver LifeLine (P1CaLL) pilot study assessed the feasibility, acceptability, and general impact of an individual telephone-based cognitive behavioral stress-management (CBSM) intervention for caregivers of phase I oncology trial patients. Methods The pilot study involved 4 weekly adapted CBSM sessions followed by participant randomization to 4 weekly cognitive behavioral therapy sessions or metta-meditation sessions. A mixed-methods design used quantitative data from 23 caregivers and qualitative data from 5 caregivers to examine the feasibility and acceptability outcomes. Feasibility was determined using recruitment, retention, and assessment completion rates. Acceptability was assessed with self-reported satisfaction with program content and participation barriers. Baseline to post-intervention changes in caregiver distress and other psychosocial outcomes were assessed for the 8-session intervention. Results The enrollment rate was 45.3%, which demonstrated limited feasibility based on an a priori criterion enrollment rate of 50%. Participants completed an average of 4.9 sessions, with 9/25 (36%) completing all sessions and an 84% assessment completion rate. Intervention acceptability was high, and participants found the sessions helpful in managing stress related to the phase 1 oncology trial patient experience. Participants showed reductions in worry and isolation and stress. Significance of results The P1CaLL study demonstrated adequate acceptability and limited feasibility and provided data on the general impact of the intervention on caregiver distress and other psychosocial outcomes. Caregivers of phase 1 oncology trial patients would benefit from supportive care services; a telephone-based intervention may have more utilization and thus make a larger impact.

The rising cost of medications has a disproportionate effect on community-dwelling older adults despite policy changes designed to improve medication access. Medicare insurance counseling provided by pharmacists, including individualized plan comparison and enrollment assistance, improves medication adherence and health care utilization, yet only 15% of community dwelling older adults report using a pharmacy or pharmacist for Medicare information. To determine what information is available to inform expanding implementation of pharmacy as a resource for Medicare insurance counseling, a systematic review of published studies using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework was conducted.Articles meeting inclusion criteria were identified through a literature search using PubMed and GoogleScholar; 27 pharmacy Medicare insurance counseling studies were identified representing 13 unique programs in clinical, community outreach, and community pharmacy settings. Each article was coded by two researchers using the RE-AIM Coding Sheet for Publications and the extent of RE-AIM dimension reporting was determined using descriptive statistics at the program level. Discussions were used to arrive at coding consensus and concordance was measured with Krippendorff's alpha.Across all studies (15 quasi experimental, 10 analytical case reports, and 2 case reports) more than half of the programs reported framework component dimensions for Reach (69%), Adoption (58%), Implementation (54%), and Maintenance (54%), and fewer than half reported comprehensively on Effectiveness (44%). Ten studies in 7 of 13 programs reported estimated out-of-pocket cost savings. Two studies measured patient-centered outcomes: medication adherence by proportion of days covered (PDC) and health care utilization by hospital admissions and emergency department visits. Gaps in the external validity of pharmacy Medicare education programs were identified including staff participation rates, methods to identify participating settings and program costs.Based on this review, current research on pharmacy Medicare education is insufficient to guide broad implementation. Additional studies are needed to determine how Medicare education integrating pharmacists and pharmacies can be implemented to address cost-related non-adherence for community dwelling older adults.

ObjectivesThe current study explored the impact of cancer-related fertility concerns on existential distress and meaning making among female breast cancer (BC) patients of childbearing age and assessed support needs.MethodsThe current study was embedded within a larger study. A seven-question online survey was administered to female BC participants to explore meaning and identity in their lives. Applied thematic analysis was used to analyze participants’ written responses.ResultsA total of 98 participants completed the survey, the majority of whom identified as white, married or partnered, and employed full time and with stage I or II BC. More than 50% of the participants expressed a need for support from a counselor or support group during their cancer experience. Three subthemes emerged related to existential distress and cancer-related fertility concerns: (1) loss of womanhood: treatment-related physical changes impact on gender identity; (2) existential distress due to treatment decisions impacting fertility; and (3) shattered vision: cancer-related infertility impact on meaning and purpose. Four subthemes emerged related to meaning making with fertility-related existential concerns: (1) coping with loss of meaning, (2) re-evaluating priorities in life; (3) resilience to loss, and (4) persistent loss of meaning.Significance of ResultsStudy results offer valuable insights into the experiences of female BC survivors’ cancer-related fertility on existential distress and meaning making. Development of psychological interventions targeted to support this population to cope with existential distress due to cancer-related fertility concerns and meaning making are needed to improve the quality of life of this population.

We estimated geometric plume heights for the daytime eruptions of La Soufrière in April 2021 using visible red band geostationary side views and geostationary–polar orbiter stereo views. Most of the plumes either spread near the tropopause at 16–17 km altitude or penetrated the stratosphere at 18–20 km altitude. Overshooting tops reached heights of up to 23 km. These geometric heights were compared with radiometric heights corresponding to the coldest plume temperature, which usually represent ambiguous estimates within a wide range between a tropospheric and a stratospheric height match. The tropospheric lower bound of the radiometric height range always underestimated the geometric height by a couple of kilometers, even for smaller plumes. For plumes near or above the tropopause, the midpoint or the stratospheric upper bound of the radiometric height range was in reasonable agreement with the geometric heights. The geometric overshooting top height, however, was always above the radiometric height range. We also found that geometric plume heights can be estimated from infrared band side views too, albeit with increased uncertainty compared to the visible red band. This opens up the possibility of applying the side view method to nighttime eruptions.

The Next Generation NCLEX® requires higher levels of understanding for new registered nurses to practice safely. Team-based learning (TBL) offers a rigorous but pragmatic approach to achieve that aim. TBL employs collaborative strategies for structured problem-solving, a key focus of contemporary nurse educators. In this prospective study, a faculty team at a second-degree, accelerated baccalaureate nursing program within the southeast United States evaluated student perspectives of TBL. Overall findings revealed positive student experiences (n = 30, with three students on an alternate plan of study) in all aspects of the method.

Background: Nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) can be detected using nasal swab polymerase chain reaction (PCR) assay and is associated with clinical MRSA infection. The MRSA nasal PCR has a rapid turnaround time and a negative predictive value for MRSA pneumonia of >98%; however, data are limited in critically ill patients. Objective: The purpose of this study is to determine the impact of a pharmacist-driven algorithm, utilizing MRSA PCR nasal screening on duration of anti-MRSA therapy in patients admitted to the intensive care unit (ICU) with suspected pneumonia. Methods: A single-center pre/post study was conducted in 4 ICUs at a large tertiary care community hospital. Adult patients admitted to the ICU initiated on vancomycin or linezolid for pneumonia managed using a pharmacist-driven MRSA PCR algorithm were included in the algorithm cohort. A historical cohort with standard management was matched 1:1 by age, type of pneumonia, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary outcome was duration of anti-MRSA therapy. Secondary outcomes included MRSA rates, number of vancomycin levels, new onset of acute kidney injury (AKI), ICU length of stay (LOS), hospital LOS, and mortality. Results: Of the 245 patients screened, 50 patients met inclusion criteria for the algorithm cohort and were matched to 50 patients in the historical cohort. The duration of anti-MRSA therapy was significantly lower compared with the historical cohort (47 vs 95 hours; P < 0.001). Secondary outcomes were similar between groups for MRSA rates, new onset of AKI, LOS, and mortality. There were less vancomycin levels ordered in the algorithm cohort (2 vs 3, P = 0.026). Conclusions: A pharmacist-driven MRSA PCR algorithm significantly reduced anti-MRSA duration of therapy in critically ill patients with pneumonia. Future studies should validate these results in critically ill populations and in settings where MRSA pneumonia is more prevalent.

PURPOSE: Up to 10% of cancers may be associated with an inherited mutation that increases cancer risk. National guidelines emphasize referral for genetic counseling and testing for patients whose personal and/or family history increases their risk of having a hereditary cancer syndrome. METHODS: To increase appropriate referrals for cancer genetic counseling and testing, we piloted an automated alert known as a Best Practice Advisory (BPA) in the electronic health record, Epic, to notify oncology providers when a patient had a personal and/or family history that merited referral to cancer genetics. Epic could not gather the complex clinical data needed for the referral decision automatically, necessitating staff completion of a questionnaire. After educating providers, the BPA was implemented with resources to support its use. RESULTS: Initial interaction with the alert was high but rapidly dwindled, resulting in questionnaire completion in 7.2% of more than 32,000 encounters and 14.9% of patients over 9 months. However, cancer genetics referrals increased 95.9% during the pilot ( P < .0001), with 18.5% placed through the BPA and the rest from a non-BPA mechanism. Semistructured interviews with key stakeholders revealed not only general acceptance of the BPA concept but also barriers to completion, such as pressure to room patients quickly in the face of competing BPAs and lack of buy-in from some providers. CONCLUSION: These results suggest that provider engagement and BPA fatigue are significant obstacles to acceptance of a new automated alert. Despite interest in a tool for cancer genetics, the demand on clinical time for this complex BPA was poorly tolerated.

Given the recent focus on powered haulage incidents within the US mining sector, an appraisal of collision avoidance/warning systems (CXSs) through the lens of the available research literature is timely. This paper describes a rapid review that identifies, characterizes, and classifies the research literature to evaluate the maturity of CXS technology through the application of a Technology Readiness Assessment. Systematic search methods were applied to three electronic databases, and relevant articles were identified through the application of inclusion and exclusion criteria. Sixty-four articles from 2000 to 2020 met these criteria and were categorized into seven CXS technology categories. Review and assessment of the articles indicates that much of the literature-based evidence for CXS technology lies within lower levels of maturity (i.e., components and prototypes tested under laboratory conditions and in relevant environments). However, less evidence exists for CXS technology at higher levels of maturity (i.e., complete systems evaluated within operational environments) despite the existence of commercial products in the marketplace. This lack of evidence at higher maturity levels within the scientific literature highlights the need for systematic peer-reviewed research to evaluate the performance of CXS technologies and demonstrate the efficacy of prototypes or commercial products, which could be fostered by more collaboration between academia, research institutions, manufacturers, and mining companies. Additionally, results of the review reveal that most of the literature relevant to CXS technologies is focused on vehicle-to-vehicle interactions. However, this contrasts with haul truck fatal accident statistics that indicate that most haul truck fatal accidents are due to vehicle-to-environment interactions (e.g., traveling through a berm). Lastly, the relatively small amount of literature and segmented nature of the included studies suggests that there is a need for incremental progress or more stepwise research that would facilitate the improvement of CXS technologies over time. This progression over time could be achieved through continued long-term interest and support for CXS technology research.

The stereo-winds method follows trackable atmospheric cloud features from multiple viewing perspectives over multiple times, generally involving multiple satellite platforms. Multi-temporal observations provide information about the wind velocity and the observed parallax between viewing perspectives provides information about the height. The stereo-winds method requires no prior assumptions about the thermal profile of the atmosphere to assign a wind height, since the height of the tracked feature is directly determined from the viewing geometry. The method is well developed for pairs of Geostationary (GEO) satellites and a GEO paired with a Low Earth Orbiting (LEO) satellite. However, neither GEO-GEO nor GEO-LEO configurations provide coverage of the poles. In this paper, we develop the stereo-winds method for multi-LEO configurations, to extend coverage from pole to pole. The most promising multi-LEO constellation studied consists of Terra/MODIS and Sentinel-3/SLSTR. Stereo-wind products are validated using clear-sky terrain measurements, spaceborne LiDAR, and reanalysis winds for winter and summer over both poles. Applications of multi-LEO polar stereo winds range from polar atmospheric circulation to nighttime cloud identification. Low cloud detection during polar nighttime is extremely challenging for satellite remote sensing. The stereo-winds method can improve polar cloud observations in otherwise challenging conditions.

Magnetic fields can have profound effects on the motion of electrons in quantum materials. Two-dimensional (2D) electron systems subject to strong magnetic fields are expected to exhibit quantized Hall conductivity, chiral edge currents, and distinctive collective modes referred to as magnetoplasmons and magnetoexcitons. Generating these propagating collective modes in charge-neutral samples and imaging them at their native nanometer length scales have thus far been experimentally elusive tasks. In this study, we visualize propagating magenetoexction polaritons at their native length scales and report their magnetic-field-tunable dispersions in near-charge-neutral graphene. Imaging of these collective modes and their associated opto-electrical responses at the sample edges is enabled by innovations to our cryogenic near-field optical microscope that allows us to nano-image the optical responses of 2D materials in magnetic fields up to 7 Tesla. This novel nano-magneto-optics approach represents a new paradigm for exploring and manipulating magnetopolaritons in specimens with low carrier doping via harnessing high magnetic fields.

Data sharing statement: The protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online at https://www.phosp.org/ Copyright © 2023 The Author(s). Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research. The study was funded with grants from UK Research and Innovation (MR/V027859/1) and The National Institute of Health Research (COV0319). This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the study at all of the 40 NHS trusts and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. The authors would also like to acknowledge the support of the eDRIS Team (Public Health Scotland) for their involvement in obtaining approvals, provisioning and linking data and the use of the secure analytical platform within the National Safe Haven.

Data sharing: The PHOSP-COVID study protocol, consent form, definition, and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online. UK Biobank information can be released once necessary approvals have been obtained. Other data (eg, the R code and protocol) will be made available on reasonable request to the corresponding author. Copyright © 2023 The Author(s). Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

This article analyzes Alex Appella’s art book published in Argentina in English as The János Book and in Spanish as Entonces el libro and Después de la carta, along with the reception of the book among “communities of response” in classrooms throughout Argentina through a program called the Biblioteca Ambulantes, or Traveling Libraries. I argue that Appella’s writing is multidirectional and nonlinear, two significant characteristics of Jewish writing that necessitate greater attention to the flow of ideas and people across borders in the Western hemisphere, such as between the United States and Argentina, as well as across the Atlantic, such as in contact with Eastern Europe or Israel. Moreover, this multidirectionality draws in “communities of response” in Argentina, even students in a largely Catholic and/or indigenous society who may have previously known little or nothing about Jewish history or the Holocaust. Thinking with the concept of “communities of response” (Davis 1997), my article means to draw attention to the many possibilities for resonance or meaning, which go beyond simple and perhaps misguided assumptions that attempt to fix the Jewishness of Appella or her writing.

Electrosurgery uses electrical energy to achieve incision, hemostasis, and resection of tissue. While electrosurgical generators have become increasingly, sophisticated they are not foolproof, and having a good understanding of how electrical principles apply to ERCP and other pancreaticobiliary interventions is essential. Here we explore the electrical principles that make sphincterotomy, ablation, stone fragmentation, and drainage of collections effective and safe.

During the 2018 House of Representatives elections, the United States saw a larger influx of minority candidates than elections in recent years. Many of these candidates were non-incumbents who ran successful campaigns against long-standing incumbents. Using the 2018 Cooperative Election Study data (CCES), we analyze the likelihood of Black voters to support White candidates over minority candidates, with a focus on incumbency status. Previous research has found that Black voters tend to display a larger affinity to support minority candidates due to theories such as group identity and racial voting. Given what is known from the literature about Black voting patterns, our study sets out to determine the extent to which incumbency matters for Black voters in the 2018 Congressional House of Representative (HOR) elections. The findings of our analysis reveal that Black voters are significantly more likely to support Democratic POC candidates, and significantly less likely to support Democratic white incumbents as compared to white voters. The findings of our study illuminate that both the affinity to support minority candidates and incumbency matter to Black voters.

As part of Geoscience Australia’s Exploring for the Future program, this study aims to analyse the hydrocarbon prospectivity in the Carrra Sub-basin through wireline log interpretation and shale gas reservoir characterisation. NDI Carrara 1 is the first stratigraphic test of the Carrara Sub-basin, a recently uncovered depocentre located within the South Nicholson region of the eastern Northern Territory and northwestern Queensland. Four chemostratigraphic packages were defined according to the informal sub-division of stratigraphy and inorganic geochemical properties. Wireline log interpretation has been conducted to derive the clay mineral compositions, porosity, gas saturation and gas contents for the unconventional shale gas reservoirs in the Proterozoic succession in NDI Carrara 1. The predominant clay minerals include illite/muscovite, mixed-layer clay, smectite, kaolinite, and minor contents of glauconite and chlorite. The average geothermal gradient is estimated to be 35.04 °C/km with a surface temperature of 29.4 °C. The average formation pressure gradient is calculated to be < 10.7 MPa/km from mud weight records. Artificial neural network technology is used to interpret the TOC content from wireline logs for unconventional shale gas reservoirs. TOC content is positively correlated with methane and ethane concentrations in mudlog gas profiles, shale porosity, formation resistivity and gas content for NDI Carrara 1. The organic-rich shales in P2 have favourable adsorbed, free and total gas contents. The organic-rich micrites within P3 have the potential in adsorbed gas, but with very low average gas saturation (< 0.01 m3/m3). Our interpretation has identified potential shale gas reservoirs, as well as tight non-organic-rich shales and siltstones with potential as gas reservoirs. These occur throughout several of the identified chemostratigraphic packages within the Proterozoic section of NDI Carrara 1.

This report presents the results of petrographic and X-ray Diffraction analysis undertaken by Microanalysis Australia under contract to Geoscience Australia, on rock samples collected from selected drill holes across the Proterozoic Birrindudu Basin and underlying metamorphic basement.

The preserved successions from the Mesoproterozoic Era (1600 to 1000 Ma) are a relatively understudied part of Australian geological evolution, especially considering that this era has a greater time span than the entire Phanerozoic. These rocks are mostly known in variably-preserved sedimentary basins overlying Paleoproterozoic or Archean cratons or at the margins of these cratons. Some metamorphosed equivalents occur within the orogens between or marginal to these cratons. Both energy and mineral resources are hosted in Australian Mesoproterozoic basins, including the highly-prospective organic rich shale units within the Beetaloo Sub-basin (Northern Territory), which form part of the Beetaloo Petroleum Supersystem. The primary aim for this record is to provide a consolidated state of knowledge of Australian basins or successions similar in age to that of the Mesoproterozoic Beetaloo Petroleum Supersystem. The findings of this report will assist prioritising future work, through improved geological understanding and resource prospectivity. This report presents an overview of 14 Mesoproterozoic-age sedimentary basins or successions and their current level of understanding, including location, basin architecture, stratigraphy and depositional environments, age constraints and mineral and energy resources. Basins or successions included in this record are unmetamorphosed or metamorphosed to very low-grade conditions. Recommendations are made for future work to address the main knowledge gaps identified from this review. While some of these basins have been the focus of recent intense study and data acquisition, the extent of knowledge varies broadly across basins. All basins reviewed in this record would benefit from further geochemical and geochronological analyses, and stratigraphic study to better understand the timing of depositional events and their correlation with nearby basins. Elucidation of the post-depositional history of alteration, migration of fluids and/or hydrocarbons would facilitate future exploration and resource evaluation.

IMPORTANCE: Low back and neck pain are often self-limited, but health care spending remains high. OBJECTIVE: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months’ duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). INTERVENTIONS: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). MAIN OUTCOMES AND MEASURES: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. RESULTS: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were −5.8 (95% CI, −7.7 to −3.9; P

Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.

Immune cells are fundamental regulators of extracellular matrix (ECM) production by fibroblasts and have important roles in determining extent of fibrosis in response to inflammation. Although much is known about fibroblast signaling in fibrosis, the molecular signals between immune cells and fibroblasts that drive its persistence are poorly understood. We therefore analyzed skin and lung samples of patients with diffuse cutaneous systemic sclerosis, an autoimmune disease that causes debilitating fibrosis of the skin and internal organs. Here, we define a critical role of epiregulin-EGFR signaling between dendritic cells and fibroblasts to maintain elevated ECM production and accumulation in fibrotic tissue. We found that epiregulin expression marks an inducible state of DC3 dendritic cells triggered by type I interferon and that DC3-derived epiregulin activates EGFR on fibroblasts, driving a positive feedback loop through NOTCH signaling. In mouse models of skin and lung fibrosis, epiregulin was essential for persistence of fibrosis in both tissues, which could be abrogated by epiregulin genetic deficiency or a neutralizing antibody. Therapeutic administration of epiregulin antibody reversed fibrosis in patient skin and lung explants, identifying it as a previously unexplored biologic drug target. Our findings reveal epiregulin as a crucial immune signal that maintains skin and lung fibrosis in multiple diseases and represents a promising antifibrotic target.

Background In December 2020, ceftolozane/tazobactam (CT) was voluntarily recalled due to failed sterility tests. With this recall, clinicians were forced to utilize alternatives for multi-drug resistant (MDR) Pseudomonas (PSA) infections until CT returned in late December, 2021. While many studies have examined the impact of medication shortages, few have evaluated the impact of antimicrobial shortages. We evaluated the impact of the CT recall by assessing cost, clinical outcomes, and utilization of novel alternative agents. Methods This multi-site retrospective cohort study compared patients treated for MDR PSA prior to the CT recall (Jan-Jul 2020) to patients treated during the CT recall (Jan-Jul 2021) across seven AdventHealth Central Florida (AHCF) adult hospitals. The primary outcome was percentage of patients treated with novel therapies (CT, ceftazidime/avibactam, or cefiderocol). Secondary outcomes included length of therapy (LOT), inpatient mortality, 30-day readmissions, length of say (LOS), pharmacy expenditures, and average cost per case. Results A total of 203 patients with MDR PSA were evaluated: 100 in the pre-recall cohort and 103 in the post-recall cohort. The majority (58%) of patients were male with an average age of 64 years. The most common source of infection in both cohorts was pneumonia, followed by complicated urinary tract infection. Significantly more patients were treated with novel agents as definitive therapy in the post-recall cohort (65% vs. 29%, p< 0.0001). Average LOT for all anti-PSA therapy was 12 days in the pre-recall cohort compared to 14 days in the post-recall cohort (p=0.1753). Inpatient mortality and 30-day readmissions were not statistically different between groups. Hospital LOS was significantly different between the two groups (18 days vs. 25 days, p=0.006). Significantly higher pharmacy expenditures were found in the post recall cohort (Figure 1) and the average cost per case was significantly higher in the post-recall cohort ($125,254 vs. $62,249). Figure 1:Pharmacy Expenditures for Novel Agents Novel agents: cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam Conclusion The CT recall had a significant impact on both economic and clinical outcomes, particularly increased length of stay, length of therapy, and cost to both the patient and health system. Higher utilization of novel agents is concerning given rising rates of PSA resistance. Disclosures Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.

Background Timely conversion of antimicrobials from intravenous (IV) to oral (PO) route has been shown to decrease costs and length of stay (LOS) without compromising safety and efficacy of therapy. Use of oral antimicrobials may additionally prevent complications related to IV catheters, such as infection, emboli, and patient discomfort. An approved IV to PO policy allowed pharmacists to convert orders for fourteen included antimicrobials and eligible patients at time of order verification. Methods This single-center, retrospective, comparative study was conducted at AdventHealth Orlando, a 1,368-bed community teaching hospital in central Florida. In November 2020, six clinical pharmacist teams began receiving monthly feedback on IV to PO conversion rates in the form of a RePOrt Card, containing IV to PO conversion rates compared to other clinical teams, individual antimicrobial conversion rates, and comparison to prior team progress (Figure 1). RePOrt Cards were provided through October 2021. This study compared pre-intervention days of therapy (DOTs) of antimicrobials from November 2019-October 2020 to post-intervention DOTs from November 2020 to March 2022. The primary objective of this study was to assess the impact of monthly, team-based feedback on percentage of antimicrobials administered orally during a pharmacist-driven IV to PO stewardship initiative. Figure 1Example RePOrt Card Results Significantly more DOTs were administered orally in the post intervention group (62% vs 67%, p=0.0012). Positive change in oral conversion rates was observed for all agents except linezolid, minocycline, and voriconazole (Table 1). The largest increase in percentage of DOT administered orally was observed for azithromycin (20%), rifampin (14%), and metronidazole (10%). Estimated monthly and total cost differences are available in Table 2. Minocycline represents the largest opportunity missed; while oral conversion rates remained the same, an increase in overall drug use creates opportunity to continue to prioritize oral conversion due to high cost. Conclusion Monthly, team-based feedback positively impacted IV to PO conversion rates. Opportunities remain to optimize cost benefits in high-cost agents such as linezolid, minocycline, and voriconazole. Disclosures Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.

Background Candida spp. are the fourth most common cause of bloodstream infections (BSI) in the United States and have an associated mortality rate of 19-40.5%. Mortality rates are further impacted by delay in time to adequate antifungal therapy, historically due to delayed time to identification on culture. The utilization of rapid diagnostic technology (RDT) has been effective in timely identification of bacterial pathogens causing BSI, but RDT for fungal organisms has demonstrated mixed results. At AdventHealth Central Florida Division South (CFD-S), pharmacists provide 24-hour coverage for real-time notification of all positive blood culture results. The objective of this study was to evaluate the clinical impact of the GenMark ePlex Blood Culture Identification Panels (BCID) fungal pathogen (FP) panel paired with 24/7, pharmacist-driven response in patients with candidemia. Methods This multi-site, pre/post, retrospective chart review included adult patients admitted to CFD-S with at least one positive blood culture with Candida spp. from June 2019 through May 2020 (pre-RDT), and August 2020 through July 2021 (post-RDT). Patients receiving systemic antifungal prophylaxis, with known candidiasis at time of index RDT result, or who discharged prior to culture positivity were excluded. The primary outcome was time to effective antifungal therapy in patients with candidemia. Results A total of 200 patients were included in the study (100 pre-RDT and 100 post-RDT). Overall, patients had a median age of 61 years and 50% were male. Patient characteristics are summarized in Table 1; median APACHEII score differed by three points (13.5 vs. 16.5). Time to effective therapy was similar between groups (39.8 vs. 38.5 hours, p=0.217). There was no difference in secondary outcomes (Table 2) other than ICU length of stay (2.5 vs. 6.0 days, p=0.033) and all-cause in-hospital mortality (15% vs. 30%, p=0.011). Conclusion Pharmacist-driven, real-time response to RDT did not significantly impact time to effective antifungal therapy in patients with candidemia. Higher rate of in-hospital mortality was likely a reflection of increased severity of illness in the post-RDT group. Disclosures Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.

Background Gram-negative (GN) bacterial resistance is an urgent global health problem. Cefiderocol (CFDC) is active against many resistant GN pathogens, including Pseudomonas aeruginosa (PA). PROVE is an ongoing international, retrospective study assessment of CFDC use for Gram-negative infections (GNI). Methods Patients were eligible if they received ≥ 72 hours of CFDC. Patient and pathogen characteristics, hospital course, and antibiotic treatment patterns were described. All-cause mortality (ACM) at 14 and 30 days and clinical cure were examined as outcomes, overall, and by key characteristics such as pathogen susceptibility (determined at the local level), patient demographics, infection site, and severity of illness. Serious adverse drug reactions (SADR) were recorded. Results To date, 123 patients treated with CFDC at 12 sites were included. Sixty-five patients had PA as a pathogen, either alone (N=45) or in combination with another pathogen (N=20) attributed to starting CFDC. The median age was 54 years; 68% were male. The most prevalent comorbidity was diabetes with end stage organ damage (N=15, 23%). CFDC was given in an ICU setting in 54 (82%) patients. Vasopressors and mechanical ventilation were required in 42% and 62%, respectively. Most (91%) PA were carbapenem resistant. The median time from a positive culture to start of CFDC was 6 days. CFDC monotherapy was used in 75%. The most common GN antibiotic class used concurrently with CFDC was aminoglycosides (N=7). Targeted therapy with CFDC against pathogens of known susceptibility with or without prior GN antibiotics accounted for 80% of use. The remainder was used for salvage (15%) or empirically (2%). Susceptibility testing to CFDC, available for 54 cultures (54 patients), showed 94% (51/54) were susceptible. Post-CFDC initiation 14- and 30-day all-cause mortality (ACM) was 9% (95% CI: 3%-19%) and 23% (95% CI: 14%-35%) respectively. Clinical resolution was achieved in 66% (95% CI: 53% -77%). Thirty-day ACM for susceptible pathogens was 25% (13/51). Cefiderocol Use Patterns in Pseudomonas aeruginosa Conclusion Real-world use of CFDC for PA demonstrated that most patients had multiple comorbidities and were severely ill. These data suggest that CFDC is being used appropriately with little empirical use in patients with few treatment options. Disclosures Stephen Marcella, MD, MPH, Shionogi: Shionogi employee|Shionogi, Inc: Employee Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board Sean Nguyen, n/a, Shionogi: Employee Anan Zhou, MPH, Shionogi, Inc: contracting work for Shionogi, Inc.

Background The use of remdesivir (RDV) in patients hospitalized with COVID-19 has resulted in a significantly shorter time to recovery, especially in patients receiving low flow oxygen. Despite the shortened time to recovery, concerns have been raised regarding the $3,120 cost of a five-day course. This price was originally justified by the suggestion that RDV would save hospitals approximately $12,000 per patient by shortening hospital length of stay (LOS) by four days, however, this has not been consistently demonstrated in clinical practice. A preliminary review of RDV orders at our facility revealed hospital discharges were being delayed to complete a five-day course of treatment in patients otherwise medically ready to discharge. Methods This single-center, retrospective, comparative study was conducted at AdventHealth Orlando, a 1,368-bed community teaching hospital in central Florida. In January 2021, the campus stewardship committee devised a RDV stewardship strategy including targeted education and escalation of orders not meeting institutional criteria at time of order verification. This study compared pre-intervention patients who received RDV from December 1, 2020, to January 7, 2021, to post-intervention patients who received RDV from January 8, 2021, to February 28, 2022. The primary objective of this study was to assess the impact of a pharmacist-driven RDV stewardship initiative on the duration of therapy in hospitalized patients with COVID-19. Results A total of 2104 remdesivir orders were included in the study (209 pre-intervention and 1895 post-intervention). Overall, patients had a median age of 59 years and 49% were male. Majority of patients in both groups required low flow supplemental oxygen at the time of RDV initiation. Significantly more orders in the intervention group aligned with institutional criteria at the time of order entry (47% vs 84%, p< .001). Patients completing the full 5-day course of remdesivir therapy decreased from 79 to 53% (p< .001). A decreased duration of therapy and length of stay were observed in the intervention group. Conclusion Pharmacist-driven RDV stewardship increased adherence to the institutional algorithm and reduced duration of therapy. Disclosures Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.

Background PROVE is an ongoing international, retrospective study assessing cefiderocol (CFDC) for Gram-negative (GN) infections. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are difficult-to-treat with limited treatment options. CFDC is a novel sidero cephalosporin with activity against CRAB. This analysis describes the outcomes and treatment patterns of CFDC treatment in CRAB infections from this study. Methods Patients were eligible if they received ≥ 72 hours of CFDC. Key patient characteristics, infecting pathogen susceptibility, illness severity, and treatment patterns were assessed. Fourteen and 30-day all-cause mortality (ACM) and clinical cure were examined as outcomes. Susceptibility testing was performed locally. Serious adverse drug reactions (SADR) were recorded. Results To date,123 patients treated with CFDC at 12 sites were included. Forty-one had monomicrobial (n=29) or polymicrobial (n=12) Acinetobacter baumannii (AB) infection. All but one were CRAB. The median age was 53 years; 71% were male. The most prevalent comorbidity was severe burns (N=9, 22%). Sixty-one percent of patients received CFDC in the ICU, 51% required mechanical ventilation, and 34% required vasopressor support. The median time from positive culture to CFDC initiation was 5 days. CFDC monotherapy was used in 61%. Tetracyclines were the most common concurrent GN antibiotics used with CFDC (N = 8, 19.5%). Targeted therapy with or without prior GN antibiotics was used in 76%, salvage in 20%, and empirical in 2%. Susceptibility results were available for 28 AB cultures from 28 patients of which 82% were susceptible to CFDC. Post-CFDC 14- and 30-day ACM was 12% (95% CI: 4%-26%) and 22% (95% CI: 11%-38%), respectively. Clinical resolution was achieved in 59% (95% CI: 42% -74%). Thirty-day ACM varied by susceptibility to CFDC: 26% for susceptible, 40% for resistant. One SADR (interstitial nephritis) was reported. Cefiderocol Use Patterns in Acinetobacter baumannii Conclusion Real-world use of CFDC for AB demonstrates that most patients were complex with multiple comorbidities and severe illness prior to treatment. It was used mostly as targeted therapy. CFDC may be a treatment option in these difficult-to-treat infections. Disclosures Stephen Marcella, MD, MPH, Shionogi: Shionogi employee|Shionogi, Inc: Employee Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board Benjamin Georgiades, PharmD, Shionogi, Inc: Employee Caroline Margiotta, MA, Shionogi, Inc: contracting work for Shionogi, Inc.

The Association for Applied and Clinical Sociology (AACS) was formed in 2005 by the merger of the Society for Applied Sociology and the Sociological Practice Association giving name recognition to both applied and clinical sociology, and a professional home for all sociological practitioners. In an effort to provide greater benefit and value to members, and to better meet the needs of its members, the AACS conducted a membership survey. On October 9, 2020, a membership survey was sent to AACS members to gather data. While the current survey results could have benefited from a greater response rate, the data gathered provides some degree of insight to members’ characteristics and attitudes toward the AACS. It is recommended that the AACS consider conducting future membership studies periodically to determine how to better meet member needs, and to estimate the value of AACS to its members.

Women diagnosed with breast cancer undergoing chemotherapy experience cognitive impairment, symptoms of anxiety and depression, and physical side effects including disruption in the diversity and community composition of the gut microbiome. To date, there is limited research exploring the associations among these specific challenges. The present cross-sectional study explored the associations of self-reported cognitive functioning, depression, and anxiety symptoms, and gut microbiome diversity and community composition in women who were diagnosed with and undergoing chemotherapy treatment for breast cancer (BC) compared to cancer-free healthy controls (HC). The BC group displayed higher rates of cognitive dysfunction (p p Akkermansia in BC compared to HC (p p

Chlorpyrifos (CPF) is an organophosphorus insecticide that has gained significant attention cue to the reported toxicity associated with developmental exposure. While the canonical mechanism of toxicity of CPF involves the inhibition of brain acetylcholinesterase (AChE), we have reported that exposure of juvenile rats to levels of CPF that do not yield any inhibition of brain AChE results in neurobehavioral alterations at later ages. However, it is unclear what effect exposure to these low levels of CPF has on blood esterase activities which are frequently used not only as biomarkers of exposure but also to set exposure levels in risk assessment. To determine this, male and female rat pups were exposed orally from postnatal day 10 to 16 to either corn oil (vehicle) or 0.5, 0.75, or 1.0 mg/kg CPF. At 12 h after the final exposure, serum cholinesterase (ChE), butyrylcholinesterase (BChE), and carboxylesterase (CES), and red blood cell (RBC) and brain AChE activities were determined. There were no differences between sexes in either the controls or individual treatments for all enzymes. Only the highest dosage of 1.0 mg/kg CPF yielded significant brain AChE inhibition (22-24%) but all dosages significantly inhibited the blood esterases with inhibition being highest with serum CES (65-85%) followed by serum BChE (57-76%), RBC AChE (35-65%), and then serum ChE (16-32%). Our data verify that blood esterases are inhibited at dosages of CPF that alter neurobehavioral performance in the absence of effects on brain AChE activity. Keywords: Chlorpyrifos (CPF); Organophosphate insecticides; Developmental; Biomarkers.