Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer.

BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape , particularly for those exhibiting mismatch repair deficiency (MMRd/MSI-H). A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. MATERIALS AND METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. RESULTS: The pooled data from 2,320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone (Hazard Ratio (HR): 0.70, 95% Confidence Interval (CI): 0.62, 0.79) across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n=563; HR: 0.33, 95% CI: 0.23, 0.43). This benefit, albeit less robust, persists in the MMRp/MSS group (n=1,757; HR: 0.74, 95% CI: 0.60, 0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR: 0.75, 95% CI: 0.63, 0.89). However, overall survival data maturity remain low. CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.

Challenges to genetic testing for germline mutations associated with breast cancer among African Americans Authors.

Inequities in preventive cancer screening, diagnosis, treatment, and inferior cancer outcomes continue to pose challenges across the cancer continuum. While the exact reasons for these inferior outcomes are unknown, multiple barriers to various domains of social determinants of health (SDOH) play a vital role, leading to inequities in cancer care. These include barriers to transportation, housing, and food insecurities, contributing to delays in preventive screening and treatment. Furthermore, aggressive biologies also exist across various racial profiles with accompanying germline mutations. For example, African Americans (AAs) have a higher incidence of triple-negative breast cancer subtype and a high prevalence of BRCA1/2 gene mutations, increasing the risk of multiple cancers, warranting high-risk screening for these populations. Unfortunately, other barriers, such as financial insecurities, low health literacy rates, and lack of awareness, lead to delays in cancer screening and genetic testing, even with available high-risk screening and risk reduction procedures. In addition, physicians receive minimal interdisciplinary training to address genetic assessment, interpretation of the results, and almost no additional training in addressing the unique needs of racial minorities, leading to suboptimal delivery of genetic assessment provision resources among AAs. In this review, we discuss the confluence of factors and barriers limiting genetic testing among AAs and highlight the prevalence of germline mutations associated with increased risk of breast cancer among AAs, reflecting the need for multi-panel germline testing as well as education regarding hereditary cancer risks in underserved minorities.

Characterization of adnexal lesions using photoacoustic imaging to improve sonographic O-RADS risk assessment.

OBJECTIVE: To assess the impact of photoacoustic imaging (PAI) on the assessment of ovarian/adnexal lesion(s) of different risk categories using the sonographic ovarian-adnexal imaging-reporting-data system (O-RADS) in women undergoing planned oophorectomy. METHOD: This prospective study enrolled women with ovarian/adnexal lesion(s) suggestive of malignancy referred for oophorectomy. Participants underwent clinical ultrasound (US) examination followed by coregistered US and PAI prior to oophorectomy. Each ovarian/adnexal lesion was graded by two radiologists using the US O-RADS scale. PAI was used to compute relative total hemoglobin concentration (rHbT) and blood oxygenation saturation (%sO2 ) colormaps in the region of interest. Lesions were categorized by histopathology into malignant ovarian/adnexal lesion, malignant Fallopian tube only and several benign categories, in order to assess the impact of incorporating PAI in the assessment of risk of malignancy with O-RADS. Malignant and benign histologic groups were compared with respect to rHbT and %sO2 and logistic regression models were developed based on tumor marker CA125 alone, US-based O-RADS alone, PAI-based rHbT with %sO2 , and the combination of CA125, O-RADS, rHbT and %sO2. Areas under the receiver-operating-characteristics curve (AUC) were used to compare the diagnostic performance of the models. RESULTS: There were 93 lesions identified on imaging among 68 women (mean age, 52 (range, 21-79) years). Surgical pathology revealed 14 patients with malignant ovarian/adnexal lesion, two with malignant Fallopian tube only and 52 with benign findings. rHbT was significantly higher in malignant compared with benign lesions. %sO2 was lower in malignant lesions, but the difference was not statistically significant for all benign categories. Feature analysis revealed that rHbT, CA125, O-RADS and %sO2 were the most important predictors of malignancy. Logistic regression models revealed an AUC of 0.789 (95% CI, 0.626-0.953) for CA125 alone, AUC of 0.857 (95% CI, 0.733-0.981) for O-RADS only, AUC of 0.883 (95% CI, 0.760-1) for CA125 and O-RADS and an AUC of 0.900 (95% CI, 0.815-0.985) for rHbT and %sO2 in the prediction of malignancy. A model utilizing all four predictors (CA125, O-RADS, rHbT and %sO2 ) achieved superior performance, with an AUC of 0.970 (95% CI, 0.932-1), sensitivity of 100% and specificity of 82%. CONCLUSIONS: Incorporating the additional information provided by PAI-derived rHbT and %sO2 improves significantly the performance of US-based O-RADS in the diagnosis of adnexal lesions. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of clinical predictions of prognosis at the end-of-life: evidence from routinely collected data in urgent care records.

BACKGROUND: The accuracy of prognostication has important implications for patients, families, and health services since it may be linked to clinical decision-making, patient experience and outcomes and resource allocation. Study aim is to evaluate the accuracy of temporal predictions of survival in patients with cancer, dementia, heart, or respiratory disease. METHODS: Accuracy of clinical prediction was evaluated using retrospective, observational cohort study of 98,187 individuals with a Coordinate My Care record, the Electronic Palliative Care Coordination System serving London, 2010-2020. The survival times of patients were summarised using median and interquartile ranges. Kaplan Meier survival curves were created to describe and compare survival across prognostic categories and disease trajectories. The extent of agreement between estimated and actual prognosis was quantified using linear weighted Kappa statistic. RESULTS: Overall, 3% were predicted to live "days"; 13% "weeks"; 28% "months"; and 56% "year/years". The agreement between estimated and actual prognosis using linear weighted Kappa statistic was highest for patients with dementia/frailty (0.75) and cancer (0.73). Clinicians' estimates were able to discriminate (log-rank p < 0.001) between groups of patients with differing survival prospects. Across all disease groups, the accuracy of survival estimates was high for patients who were likely to live for fewer than 14 days (74% accuracy) or for more than one year (83% accuracy), but less accurate at predicting survival of "weeks" or "months" (32% accuracy). CONCLUSION: Clinicians are good at identifying individuals who will die imminently and those who will live for much longer. The accuracy of prognostication for these time frames differs across major disease categories, but remains acceptable even in non-cancer patients, including patients with dementia. Advance Care Planning and timely access to palliative care based on individual patient needs may be beneficial for those where there is significant prognostic uncertainty; those who are neither imminently dying nor expected to live for "years".

Defining piscine endpoints: Towards score sheets for assessment of clinical signs in fish research.

The seminar 'Severity and humane endpoints in fish research' organized by the University of Bergen, the Industrial and Aquatic Laboratory, together with Fondazione Guido Bernadini, took place on 4 October 2019 in Bergen, Norway. The seminar was followed by a workshop, 'Establishing score sheets and defining endpoints in fish experiments', held on 28 January 2020, also in Bergen. The purpose of the seminar was to raise awareness about fish ethics together with severity classification and humane endpoints in fish studies, using examples from farmed fish, mainly salmonids and lumpfish. The overall aim of the workshop was to better define humane endpoints in fish experiments, as well as to discuss suggestions for development and use of score sheets for assessing clinical signs related to endpoints. Endpoints for fish should not only be based on what we know about fish diseases and the lesions they induce but should also take into consideration knowledge about fish species and life stage, fish anatomy, physiology and the general state and behaviour of the fish. For this reason, to reinforce that endpoints should come from the animal's perspective and needs, we renamed humane endpoints for fish to piscine endpoints. This paper reports the main messages from the workshop sessions including advice on development and use of score sheets.

Radiotherapy Quality Assurance in the PORTEC-3 (TROG 08.04) Trial.

AIMS: Quality assurance in radiotherapy (QART) is essential to ensure the scientific integrity of a clinical trial. This paper reports the findings of the retrospective QART assessment for all centres that participated in PORTEC-3; a randomised controlled trial that compared pelvic radiotherapy with concurrent chemoradiotherapy to the pelvis followed by adjuvant chemotherapy. The trial showed an overall survival benefit for the addition of the chemotherapy in the management of women with high-risk endometrial cancer. MATERIALS AND METHODS: Clinicians were invited to upload a randomly selected case/s treated at each of the participating sites. Panel reviewers analysed the contours to certify that the target volumes and organ at risk structures were contoured according to guidelines. The results were categorised into acceptable, minor variation, major variation or unevaluable. The radiotherapy plans were dosimetrically evaluated using the well-established Trans-Tasman Radiation Oncology Group (TROG) protocol. RESULTS: Between August 2010 and January 2018, data from 146 patients of 686 consecutively treated patients were retrospectively reviewed. All 16 Australia and New Zealand and 71 of 77 international centres uploaded data for evaluation. In total, 3514 dosimetric and contour variables were reviewed. Of these, 3136 variables were deemed acceptable (89.2%), with 335 minor (9.6%) and 43 major variations (1.2%). Major contour variations included the clinical target volume vaginal vault, clinical target volume parametria and differential planning target volume vault expansion. CONCLUSION: The results of the QART assessment confirmed high uniformity and low rates of both minor and major deviations in contouring and dosimetry in all sites. This supports the safe introduction of the PORTEC-3 treatment protocol into routine clinical practice.

Radiation therapy for vaginal and perirectal lesions in recurrent ovarian cancer.

The role for localized radiation to treat ovarian cancer (OC) patients with locally recurrent vaginal/perirectal lesions remains unclear, though we hypothesize these patients may be salvaged locally and gain long-term survival benefit. We describe our institutional outcomes using intensity modulated radiation therapy (IMRT) +/- high-dose rate (HDR) brachytherapy to treat this population. Our primary objectives were to evaluate complete response rates of targeted lesions after radiation and calculate our 5-year in-field control (IFC) rate. Secondary objectives were to assess radiation-related toxicities, chemotherapy free-interval (CFI), as well as post-radiation progression-free (PFS) and overall survival (OS). PFS and OS were defined from radiation start to either progression or death/last follow-up, respectively. This was a heavily pre-treated cohort of 17 recurrent OC patients with a median follow-up of 28.4 months (range 4.5-166.4) after radiation completion. 52.9% had high-grade serous histology and 4 (23.5%) had isolated vaginal/perirectal disease. Four (23.5%) patients had in-field failures at 3.7, 11.2, 24.5, and 27.5 months after start of radiation, all treated with definitive dosing of radiation therapy. Patients who were platinum-sensitive prior to radiation had similar median PFS (6.5 vs. 13.4 months, log-rank p = 0.75), but longer OS (71.1 vs 18.8 months, log-rank p = 0.05) than their platinum-resistant counterparts. Excluding patients with low-grade histology or who were treated with palliative radiation, median CFI was 14.2 months (range 4.7 - 33.0). Radiation was well tolerated with 2 (12.0%) experiencing grade 3/4 gastrointestinal/genitourinary toxicities. In conclusion, radiation to treat locally recurrent vaginal/perirectal lesions in heavily pre-treated OC patients is safe and may effectively provide IFC.

Economic impact on direct healthcare costs of missing opportunities for diagnosing HIV within healthcare settings.

BACKGROUND: The economic consequences of a missed opportunity for HIV testing at an earlier stage of infection within a healthcare setting are poorly described. METHODS: For all newly diagnosed HIV patients followed at the Southern Alberta HIV/AIDS Clinic (SAC), Calgary, Canada, between 1 April 2011 and 1 April 2016, all clinical encounters occurring < 3 years prior to diagnosis within the region were obtained. The direct costs of HIV care after diagnosis to 31 March 2019 were determined from a payers' perspective and reported as mean cost per patient per month (PPPM) in 2019 Canadian dollars (CDN$). Patients with no encounters for 3 years prior to diagnosis were compared with patients with encounters, with special attention to patients with HIV clinical indicator conditions (HCICs). RESULTS: Of 388 patients, 60% had one or more prior encounter without HIV testing; 14% had been treated for an HCIC. Females, older patients and heterosexuals were more likely to have prior encounters. At diagnosis, patients with previous encounters presented with lower CD4 counts and higher rates of AIDS. The mean PPPM costs for patients with any prior encounter or for an HCIC-based encounter were 16% and 33% higher, respectively, than for patients with no prior encounters. While mean PPPM costs for antiretroviral drugs and outpatient visits were slightly higher, in-patient costs were 10 times higher for people with HIV who had a previous HCIC encounter vs. those with no encounters (CDN$316 vs. $31, respectively). CONCLUSIONS: Any healthcare visit, especially for an HCIC, represents relatively easy opportunities for HIV testing. Not testing can result in poorer health and higher costs. Targeted clinical testing and novel interventions to correct overlooked testing opportunities within healthcare settings may be an easy way to implement cost savings.

Molecular characterization of plasmids encoding blaCTX-M from faecal Escherichia coli in travellers returning to the UK from South Asia.

BACKGROUND: The global prevalence of extended-spectrum beta-lactamase-producing Escherichia coli is rising and is dominated by blaCTX-M spread by plasmids. Travellers to South Asia from Western Europe have high rates of acquisition of faecal CTX-M-producing E. coli (CTX-M-EC). AIMS: To determine the conjugative ability of CTX-M-EC acquired by healthy volunteers after travel to South Asia, the proportion of travel-acquired CTX-M-EC where blaCTX-M is encoded on a plasmid vs on the bacterial chromosome, and the relatedness of travel-acquired CTX-M-EC plasmids to previously sequenced plasmids. METHODS: Faecal samples were collected pre- and post-travel from 23 volunteers who visited South Asia, and CTX-M-EC were cultured. After short- and long-read sequencing, 10 plasmid sequences were identified and compared with previously sequenced plasmids in GenBank. Conjugation to E. coli K-12 was undertaken using filter mating. FINDINGS: Thirty-five percent of CTX-M-EC isolates tested transferred the blaCTX-M plasmid by conjugation. Travel-acquired CTX-M-EC carried blaCTX-M on a plasmid in 62% of isolates, whereas 38% of isolates had blaCTX-M on the chromosome. CTX-M-EC plasmids acquired after travel to South Asia had close homology to previously described epidemic plasmids which are widely disseminated in humans, animals and the natural environment. CONCLUSION: Globally successful epidemic plasmids are involved in the spread of CTX-M-EC. Targeted strategies may be used to displace such plasmids from the host strain as part of efforts in infection prevention and control in healthcare settings. Bacteria with blaCTX-M plasmids were readily acquired by healthy volunteers, and were carried on return to the UK, providing opportunities for onward dissemination.

COVID-19 lockdown: a rare opportunity to establish baseline pollution level of air pollutants in a megacity, India.

This paper analyses air quality data from megacity Delhi, India, during different periods related to the COVID-19, including pre-lockdown, lockdown and unlocked (post-lockdown) (2018-2020) to determine what baseline levels of air pollutants might be and the level of impact that could be anticipated under the COVID-19 lockdown emission scenario. The results show that air quality improved significantly during the lockdown phases, with the most significant changes occurring in the transportation and industrially dominated areas. A pronounced decline in PM2.5 and PM10 up to 63% and 58%, respectively, was observed during the lockdown compared to the pre-lockdown period in 2020. When compared to 2018 and 2019, they were lower by up to 51% and 61%, respectively, dropping by 56% during unlock. Some pollutants (NOx and CO) dropped significantly during lockdown, while SO2 and O3 declined only slightly. Moreover, when compared between the different phases of lockdown, the maximum decline for most of the pollutants and air quality index occurred during the lockdown phase 1; thus, this period was used to report the COVID-19 baseline threshold values (CBT; threshold value is the upper limit of baseline variation). Of the various statistical methods used median + 2 median absolute deviation (mMAD) was most suitable, indicating CBT values of 143 and 75 ug/m3 for PM10 and PM2.5, respectively. This results although preliminary, but it gives a positive indication that temporary lockdown can be considered as a boon to mitigate the damage we have done to the environment. Also, this baseline levels can be helpful as a first line of information to set future target limits or to develop effiective management policies for achieving better air quality in urban centres like Delhi. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-021-03142-3.

Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response.

AIMS: A complete metabolic response (CMR) on early post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a positive prognostic factor for cervical cancer patients treated with definitive chemoradiation, but long-term outcomes of this group of patients are unknown. Patterns of failure and risk subgroups are identified. MATERIALS AND METHODS: Patients who received curative-intent chemoradiation from 1998 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IVA cervical cancer and had a CMR on post-treatment FDG-PET within 5 months of treatment completion were included. Cox proportional hazards models determined factors associated with locoregional and distant failure. Kaplan-Meier estimates of freedom from any recurrence (FFR) of patient subgroups were compared with Log-rank tests. RESULTS: There were 402 patients with a CMR after chemoradiation on FDG-PET. Initial T stage was T1 (38%)/T2 (40%)/T3 (20%)/T4 (2%); initial FDG-avid nodal status was no nodes (50%)/pelvic lymph nodes (40%)/pelvic and para-aortic lymph nodes (10%). After a median follow-up of 6 years, 109 (27%) recurred. The pattern of recurrence was locoregional (27%), distant (61%) or both (12%). No factors were associated with locoregional failure. Distant recurrence was more likely in patients with T3-4 lesions (hazard ratio = 2.4, 95% confidence interval 1.5-3.8) and involvement of pelvic (hazard ratio = 1.6, 95% confidence interval 1.0-2.7) or para-aortic lymph nodes (hazard ratio = 2.7, 95% confidence interval 1.4-5.0) at diagnosis. The 5-year FFR rates for T1-2 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 85, 76 and 62%, respectively (P = 0.04, none versus para-aortic nodes). The 5-year FFR for T3-4 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 68, 56 and 25%, respectively (P = 0.09, none versus para-aortic nodes). CONCLUSIONS: T3-4 tumours and para-aortic nodal involvement at diagnosis are poor prognostic factors, even after a CMR following chemoradiation.

Insight into the chemistry of TNT during shock compression through ultrafast absorption spectroscopies.

Thin films of trinitrotoluene (TNT) were shock compressed using the ultrafast laser shock apparatus at Los Alamos National Laboratory. Visible (VIS) and mid-infrared (MIR) transient absorption spectroscopies were simultaneously performed to probe for electronic and vibrational changes during shock compression of TNT. Three shock pressures (16 GPa, 33 GPa, and 45 GPa) were selected to observe no reaction, incipient reaction, and strongly developed reactions for TNT within the experimental time scale of <250 ps. Negligible absorption changes in MIR or VIS absorptions were observed at 16 GPa. At 33 GPa, MIR absorptions in the 3000 cm-1-4000 cm-1 range were observed to increase during the shock and continue to increase during the rarefaction, in contrast to the VIS absorption measurements, which increased during the shock and almost fully recovered during rarefaction. At 45 GPa, both VIS and MIR absorptions were strong and irreversible. The intense and spectrally broad MIR absorptions were attributed to short lived intermediates with strong, spectrally broad absorptions that dominate the spectral response. The MIR and VIS absorption changes observed at 33 GPa and 45 GPa were credited to shock induced chemistry, most likely including the formation of a very broad hydrogenic stretch feature. The results from these experiments are consistent with the chemical mechanisms that include O-H or N-H formation such as CH3 oxidation or C-N homolysis.

Understanding Reentrance in Frustrated Magnets: The Case of the Er_{2}Sn_{2}O_{7} Pyrochlore.

Reentrance, the return of a system from an ordered phase to a previously encountered less-ordered one as a controlled parameter is continuously varied, is a recurring theme found in disparate physical systems, yet its microscopic cause is often not investigated thoroughly. Here, through detailed characterization and theoretical modeling, we uncover the microscopic mechanism behind reentrance in the strongly frustrated pyrochlore antiferromagnet Er_{2}Sn_{2}O_{7}. We use single crystal heat capacity measurements to expose that Er_{2}Sn_{2}O_{7} exhibits multiple instances of reentrance in its magnetic field B vs temperature T phase diagram for magnetic fields along three cubic high symmetry directions. Through classical Monte Carlo simulations, mean field theory, and classical linear spin-wave expansions, we argue that the origins of the multiple occurrences of reentrance observed in Er_{2}Sn_{2}O_{7} are linked to soft modes. These soft modes arise from phase competition and enhance thermal fluctuations that entropically stabilize a specific ordered phase, resulting in an increased transition temperature for certain field values and thus the reentrant behavior. Our work represents a detailed examination into the mechanisms responsible for reentrance in a frustrated magnet and may serve as a template for the interpretation of reentrant phenomena in other physical systems.

Information Gathering in Investigative and Medical Interviewing: Drawing Parallels Across Contexts.

Information gleaned from a patients' medical history is a core determinant of a medical diagnosis. Accurate and effective history-taking is, therefore, a foundational skill for medical practitioners and is introduced early in medical training. Recognizing and developing the skills of effective medical interviewing is an ongoing challenge for medical students and experienced clinicians alike. Important parallels exist between the information gathering skills required in medicine and health, and those required in investigative interviewing. Qualitative interviews were conducted with 19 experienced medical professionals from a range of specialty areas. They were asked about the role of the medical interview in their discipline, and about challenges they experience when gathering information from patients. Both theory-driven and grounded-theory approaches were used in combination to identify common themes. The interviews were rich with themes including approaches to introductory phases of the interview, eliciting a narrative account, and several topics that specifically paralleled issues in interviewing of vulnerable witnesses. We explore these themes through a lens of investigative interviewing by applying the knowledge of effective interviewing skills and structures to the data gained from the medical context. In general, themes indicated that there are numerous parallels to information gathering approaches in both contexts. As such, there may be scope for medical education to adopt some of the training techniques employed in the investigative interviewing field. Further, it is hoped that the present findings be used to spark an interdisciplinary conversation about communication from which both sides can learn.

General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial.

BACKGROUND: In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. METHODS: A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. RESULTS: Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). CONCLUSIONS: General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.

NeuroDAC: an open-source arbitrary biosignal waveform generator.

Objective.Researchers are developing biomedical devices with embedded closed-loop algorithms for providing advanced adaptive therapies. As these devices become more capable and algorithms become more complex, tasked with integrating and interpreting multi-channel, multi-modal electrophysiological signals, there is a need for flexible bench-top testing and prototyping. We present a methodology for leveraging off-the-shelf audio equipment to construct a biosignal waveform generator capable of streaming pre-recorded biosignals from a host computer. By re-playing known, well-characterized, but physiologically relevant real-world biosignals into a device under test, researchers can evaluate their systems without the need for expensivein vivoexperiments.Approach.An open-source design based on the proposed methodology is described and validated, the NeuroDAC. NeuroDAC allows for 8 independent channels of biosignal playback using a simple, custom designed attenuation and buffering circuit. Applications can communicate with the device over a USB interface using standard audio drivers. On-board analog amplitude adjustment is used to maximize the dynamic range for a given signal and can be independently tuned for each channel.Main results.Low noise component selection yields a no-signal noise floor of just 5.35 ± 0.063. NeuroDAC's frequency response is characterized with a high pass -3 dB rolloff at 0.57 Hz, and is capable of accurately reproducing a wide assortment of biosignals ranging from EMG, EEG, and ECG to extracellularly recorded neural activity. We also present an application example using the device to test embedded algorithms on a closed-loop neural modulation device, the Medtronic RC+S.Significance.By making the design of NeuroDAC open-source we aim to present an accessible tool for rapidly prototyping new biomedical devices and algorithms than can be easily modified based on individual testing needs.ClinicalTrials.gov Identifiers: NCT04281134, NCT03437928, NCT03582891.

Insight into the Chemistry of PETN Under Shock Compression Through Ultrafast Broadband Mid-Infrared Absorption Spectroscopy.

Thin films of pentaerythritol tetranitrate (PETN) were shock compressed using the laser driven shock apparatus at Los Alamos National Laboratory (LANL). Two spectroscopic probes were available to this apparatus: visible white light transient absorption spectroscopy (VIS) from 400 to 700 nm and mid-infrared transient absorption spectroscopy (MIR) from 1150 to 3800 cm-1. Important PETN vibrational modes are the symmetric and antisymmetric NO2 stretches at 1280 and 1650 cm-1, respectively, as well as CH stretches at ∼2900 cm-1. Shock strength was varied from approximately 3 to 55 GPa to span from the chemically unreactive regime to the regime in which fast chemical reaction took place on the 250 ps time scale of the measurements. VIS and MIR results suggest irreversible chemistry was induced in PETN at pressures above 30 GPa. At lower shock pressures, the spectroscopy showed minimal changes attributable to pressure induced effects. Under the higher-pressure reactive conditions, the frequency region at the antisymmetric NO2 stretch mode had a significantly increased absorption while the region around the symmetric NO2 stretch did not. No observable increased absorption occurred in the higher frequency regions where CH-, NH-, and OH- bond absorptions would be observed. A broad absorption appeared on the shoulder at the red-edge of the CO2 vibrational band around 2200 cm-1. In addition to the experiments, reactive molecular dynamics were carried out under equivalent shock conditions to correlate the evolution of the infrared spectrum to molecular processes. The simulations show results consistent to experiments up to 30 GPa but suggest that NO and NO2 related features provided the strongest contributions to the shocked infrared changes. Proposed mechanisms for shocked PETN chemistry are analyzed as consistent or inconsistent with the data presented here. Our experimental data suggests C≡O or N2O bond formation, nitrite formation, and absence of significant hydroxyl or amine concentrations in the initial chemistry steps in PETN shocked above 30 GPa.

The identification of sulfide oxidation as a potential metabolism driving primary production on late Noachian Mars.

The transition of the martian climate from the wet Noachian era to the dry Hesperian (4.1-3.0 Gya) likely resulted in saline surface waters that were rich in sulfur species. Terrestrial analogue environments that possess a similar chemistry to these proposed waters can be used to develop an understanding of the diversity of microorganisms that could have persisted on Mars under such conditions. Here, we report on the chemistry and microbial community of the highly reducing sediment of Colour Peak springs, a sulfidic and saline spring system located within the Canadian High Arctic. DNA and cDNA 16S rRNA gene profiling demonstrated that the microbial community was dominated by sulfur oxidising bacteria, suggesting that primary production in the sediment was driven by chemolithoautotrophic sulfur oxidation. It is possible that the sulfur oxidising bacteria also supported the persistence of the additional taxa. Gibbs energy values calculated for the brines, based on the chemistry of Gale crater, suggested that the oxidation of reduced sulfur species was an energetically viable metabolism for life on early Mars.

Effects of a mannan-rich yeast cell wall-derived preparation on cecal concentrations and tissue prevalence of Salmonella Enteritidis in layer chickens.

Salmonella Enteritidis (SE) has been the most common Salmonella serotype associated with foodborne infections in the last several years. Dietary applications of yeast-based preparations in feed have shown to reduce Salmonella colonization in chickens augmenting SE control strategies. This study was conducted to evaluate the effects of a mannan-rich yeast cell wall-derived preparation (Actigen®) administered in feed at a rate of 400 g/ton on SE colonization in the cecum and internal organs of commercial layer chickens. Sixteen week-old layer pullets were orally challenged with a selected nalidixic acid resistant SE strain at a dose of 1.7×10^9 colony forming units (CFU) per bird. SE colonization was assessed by evaluating isolation rates from ovary and pooled liver/spleen samples as well as enumeration of SE in cecal pouches one week post-challenge. Recovery rates of SE from the ovaries of directly challenged birds receiving Actigen® were significantly lower (P <0.02) than those in directly challenged birds fed an unsupplemented control diet. Recovery rates of SE from pooled liver/spleen samples were not significantly different between Actigen®-treated pullets and controls (P = 0.22). Using direct plate count methods, cecal SE concentrations were 1 log10 lower (P <0.001) in challenged pullets in the Actigen®-supplemented group than in the challenged controls. The SE concentration distributions in the ceca were similar in groups testing positive and groups testing negative for SE in the ovaries and liver/spleens tissues. As a result, SE concentrations in the ceca could not be directly related to the occurrence or prevalence of SE in these tissues. In conclusion, Actigen® supplementation appears to decrease the prevalence of SE in ovarian tissue and concentrations of SE in cecal contents and may be useful as a tool for reducing the risk of eggshell contamination and transovarian transmission of SE in eggs.