Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium.

Polycyclic aromatic hydrocarbons (PAHs) contain ≲20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures ≳1000 kelvin), by reactions within cold (~10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-13C substituted compositions (Δ2×13C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51‰ higher than values expected for a stochastic distribution of isotopes. The Δ2×13C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Δ2×13C values consistent with formation by higher-temperature reactions.

Barriers to Mammography Screening among Black Women at a Community Health Center in South Florida, USA.

Background: In the United States (US), Black/African American women suffer disproportionately from breast cancer health disparities with a 40% higher death rate compared to White women. Mammography screening is considered a critical tool in mitigating disparities, yet Black women experience barriers to screening and are more likely to be diagnosed with advanced-stage breast cancer. The purpose of this study was to assess the relative frequency of mammography screening and to examine perceived and actual barriers to screening among women who receive care in our nurse-led community health center. Methods: We conducted a survey examining frequency of mammography screening and beliefs about breast cancer including perceived susceptibility, perceived benefits, and perceived barriers to mammography screening, guided by the Champion Health Belief Model. Results: A total of 30 Black/African American women completed the survey. The mean age of the participants was 54.3 years ± 9.17 (SD); 43.3% had a high school education or less; 50% had incomes below $60,000 per year; 26.7% were uninsured; 10% were on Medicaid; and only 50% were working full-time. We found that only half of the participants reported having annual mammograms 16 (53.3%), 1 (3.3%) every 6 months, 8 (26.6%) every 2-3 years, and 5 (16.7%) never had a mammogram in their lifetime. Frequently cited barriers included: 'getting a mammogram would be inconvenient for me'; 'getting a mammogram could cause breast cancer'; 'the treatment I would get for breast cancer would be worse than the cancer itself'; 'being treated for breast cancer would cause me a lot of problems'; 'other health problems would keep me from having a mammogram'; concern about pain with having a mammogram would keep me from having one; and not being able to afford a mammogram would keep me from having one'. Having no health insurance was also a barrier. Conclusion: This study found suboptimal utilization of annual screening mammograms among low-income Black women at a community health center in Florida and women reported several barriers. Given the high mortality rate of breast cancer among Black/African American women, we have integrated a Patient Navigator in our health system to reduce barriers to breast cancer screening, follow-up care, and to facilitate timely access to treatment, thus ultimately reducing breast cancer health disparities and promoting health equity.

Sequential measurement of 13 C, 15 N, and 34 S isotopic composition on nanomolar quantities of carbon, nitrogen, and sulfur using nano-elemental analysis/isotope ratio mass spectrometry.

RATIONALE: We report modifications to a commercial elemental analyzer-isotope ratio mass spectrometer that permit high-precision isotopic analysis of nanomoles of carbon (C), nitrogen (N), and sulfur (S) on a single sample without chemical or cryogenic trapping of gases. The sample size required for measurement by our system is about two orders of magnitude less than that for conventional analyses. METHODS: Our system builds on the analytical advancements offered by the EA IsoLink IRMS System and employs simple modifications to reduce the diameter of the flow path (reactors, water trap, and transfer lines), enhance peak separation (gas chromatography capillary column), and improve sample transfer to the ion source of the mass spectrometer (reduced flow rates). RESULTS: Conventional precision (<0.2‰) can be achieved down to c. 500 nmol C, N, and S for samples analyzed without modification of the commercial system. Further reduction in sample size (<50 nmol C, N, and S) was achieved with minor modifications. There is a significant carbon blank and a small nitrogen blank that can be measured directly and a sulfur blank that can be calculated using regression. Only 30 nmol of N, 22 nmol of C, and 12 nmol of S are needed to achieve better than 1‰ precision (1σ) from a single measurement. Larger samples and more replicate measurements provide better precision. CONCLUSIONS: The nano-EA method described here reduces sample size requirements by two orders of magnitude compared to traditional approaches and improves the accuracy and precision of isotope measurements on sample sizes less than 1 µmol. These advancements simplify the analytical technique and broaden the range and type of samples amenable to EA analysis.

Preferential Retention and Transport of Perfluorooctanesulfonic Acid in a Dolomite Aquifer.

Per- and polyfluoroalkyl substances (PFAS) can represent a significant human health risk if present in aquifers used as a drinking water source. Accurate assessment of PFAS exposure risks requires an improved understanding of field-scale PFAS transport in groundwater. Activities at a former firefighter training site in University Park, Pennsylvania introduced perfluorooctanesulfonic acid (PFOS) to the underlying dolomite aquifer. Groundwater sampling from 2015 to 2018 delineated a PFOS plume with two concentration maxima located approximately 20 and approximately 220 m downgradient of the training site, separated by a zone of lower concentrations. We use a combination of analytical and numerical models, informed by independent measurements of aquifer porosity, hydraulic conductivity, and organic carbon content, to interpret the field observations. Our analysis demonstrates that preferential retention and transport resulting from simple heterogeneity in bedrock sorption, as caused by organic carbon (OC) content variability, provides a plausible explanation for plume separation. Dissolved PFOS partitions strongly to organic solids (high Koc ), so even a small OC (<1 wt%) significantly retards PFOS transport, whereas zones with little to no OC allow for transport rates that approximate those of a conservative solute. Our work highlights an important consideration for modeling the groundwater transport of PFOS, and other compounds with high Koc . In aquifers with discrete layers of varying OC, models using a uniform site-average OC will underestimate transport distances, thereby misrepresenting exposure risks for downgradient communities.

The Effect of a Brief Physician-Delivered Neurobiologically Oriented, Cognitive Behavioural Therapy (Brief-CBT) Intervention on Chronic Pain Acceptance in Youth with Chronic Pain-A Randomized Controlled Trial.

At the Stollery Children's Chronic Pain Clinic, new referrals are assessed by an interdisciplinary team. The final part of the intake assessment typically involves an explanation and compassionate validation of the etiology of chronic pain and an invitation to the youth to attend the group outpatient Cognitive Behavioural Therapy (CBT) program, called Pain 101, or to individual outpatient CBT. It was hypothesized that a brief physician-delivered CBT (brief-CBT) intervention at first point of contact improves subsequent pain acceptance. Using a randomized double blinded methodology, 26 participants received a standard intake assessment and 26 the standard assessment plus the brief-CBT intervention. Measures were taken at three points: pre and post-intake assessment and after Pain 101 or individual CBT (or day 30 post-assessment for those attending neither). The primary outcome measure was the Chronic Pain Acceptance Questionnaire­Adolescent version (CPAQ-A). Comparing pre and post-intake measures, there was a significant (p = 0.002) increase in the CPAQ-A scores­four-fold more in the brief-CBT intervention group (p = 0.045). Anxiety (RCADS-T Score) was significantly reduced post-intake and significantly more reduced in the intervention group compared to the control group (p = 0.024). CPAQ-A scores were significantly increased (p < 0.001) (N = 28) and anxiety (RCADs-T) was significantly reduced by the end of Pain 101 (p < 0.003) (N = 29) as was fear of pain as measured by the Tampa Scale for Kinesiophobia (p = 0.021). A physician-delivered brief-CBT intervention significantly and meaningfully increased CPAQ-A scores and reduced anxiety in youth with chronic pain. Furthermore, CBT through Pain 101 is effective at increasing acceptance, as well as reducing anxiety and fear of movement.

Associations between Florida counties' COVID-19 case and death rates and meaningful use among Medicaid providers: Cross-sectional ecologic study.

Although the Health Information Technology for Economic and Clinical Health (HITECH) Act has accelerated adoption of Electronic Health Records (EHRs) among Medicaid providers, only half achieved Meaningful Use. Furthermore, Meaningful Use' impact on reporting and/or clinical outcomes remains unknown. To address this deficit, we assessed the difference between Medicaid providers who did and did not achieve Meaningful Use regarding Florida county-level cumulative COVID-19 death, case and case fatality rates (CFR), accounting for county-level demographics, socioeconomic and clinical markers, and healthcare environment. We found that cumulative incidence rates of COVID-19 deaths and CFRs were significantly different between the 5025 Medicaid providers not achieving Meaningful Use and the 3723 achieving Meaningful Use (mean 0.8334/1000 population; SD = 0.3489 vs. mean = 0.8216/1000; SD = 0.3227, respectively) (P = .01). CFRs were .01797 and .01781, respectively, P = .04. County-level characteristics independently associated with increased COVID-19 death rates and CFRs include greater concentrations of persons of African American or Black race, lower median household income, higher unemployment, and higher concentrations of those living in poverty and without health insurance (all P < .001). In accordance with other studies, social determinants of health were independently associated with clinical outcomes. Our findings also suggest that the association between Florida counties' public health outcomes and Meaningful Use achievement may have had less to do with using EHRs for reporting of clinical outcomes and more to do with using EHRs for coordination of care-a key measure of quality. The Florida Medicaid Promoting Interoperability Program which incentivized Medicaid providers towards achieving Meaningful Use, has demonstrated success regarding both rates of adoption and clinical outcomes. Because the Program ends in 2021, we support programs such as HealthyPeople 2030 Health IT which address the remaining half of Florida Medicaid providers who have not yet achieved Meaningful Use.

Recommendation on Orbiting Sample Cleanliness.

The National Aeronautics and Space Administration-European Space Agency (NASA-ESA) Mars Sample Return (MSR) campaign involves the collection of samples on Mars by the Perseverance (Mars 2020) rover and their return to Earth. To accomplish this, the Orbiting Sample container (OS) will be sent to Mars to accommodate the collected samples then launched from Mars and returned to Earth, where the samples will be removed for examination in the Sample Return Facility (SRF). Crucial to this entire sequence will be establishment of the required level of cleanliness inside the OS. In February 2021, the NASA Headquarters' Mars Sample Return Program and Office of Planetary Protection assembled an MSR OS Tiger Team (OSTT) to discuss the appropriate cleanliness level options of the interior of the OS. The team's remit was primarily focused on evaluating the trade-offs between Planetary Protection cleanliness levels 4a and 4b. These cleanliness levels are determined by the Committee on Space Research (COSPAR) planetary protection regulations, where 4a requires <300 bacterial spores/m2 and <3 x 105 bacterial spores on the spacecraft (in this case, the interior of the OS) and 4b mandates the more stringent requirement of <30 bacterial spores on the spacecraft. This report documents the consensus opinion submitted by the OSTT that recommended the interior of the OS be cleaned to a 4a requirement with any feasible added effort toward 4b. This report provides, as well, the rationale for that decision.

Occupational Therapist Treatment of Patients in the Neurological Critical Care Unit: Utilization and Patient Characteristics.

IMPORTANCE: Occupational therapy use in the neurological critical care unit (NCCU) may relate to patient factors, but data about these relationships remain unpublished. OBJECTIVE: To examine how patient factors predict NCCU occupational therapy use and intervention types. DESIGN: Retrospective cohort study of electronic health records data from adults admitted to the NCCU between May 2013 and September 2015. SETTING: NCCU in a large, urban academic hospital. PARTICIPANTS: Adults (age ≥18 yr; N = 1,134) admitted to the NCCU. MEASURES: Using length of stay (LOS), number of comorbidities, Glasgow Coma Scale (GCS) score, gender, age, and racial-ethnic minority status as independent variables, separate regression models identified predictors for each dependent variable: receipt of NCCU occupational therapy, occupational therapy onset (days after admission), and receipt of self-care or home management (ADL-Home); functional activities or cognitive training (Func-Cog); and therapeutic exercise (Ther-Ex). RESULTS: Four hundred twenty patients (37.0%) received occupational therapy in the NCCU. Receipt of occupational therapy was positively associated with LOS, number of comorbidities, GCS score, and age. Earlier occupational therapy onset was associated with higher GCS score and shorter LOS. Receipt of ADL-Home or Func-Cog interventions was significantly predicted by number of occupational therapy sessions, but patients with longer LOS were less likely to receive ADL-Home interventions. Receipt of Ther-Ex interventions became less likely as GCS score increased. CONCLUSIONS AND RELEVANCE: Patients are more likely to receive occupational therapy services if they are older and have a longer NCCU LOS, more comorbidities, and a higher level of consciousness. What This Article Adds: A patient's level of consciousness is clearly associated with occupational therapy utilization and hospital outcomes, but it should not be the only factor considered when prioritizing patients for NCCU occupational therapy services. Compared with patients who were more awake and alert, patients with a lower level of consciousness had a later onset of occupational therapy, which suggests an opportunity for NCCU occupational therapists to collaborate with physicians in the modification of sedation protocols to enable early rehabilitation.

Single Word Intelligibility of Individuals with Parkinson's Disease in Noise: Pre-Specified Secondary Outcome Variables from a Randomized Control Trial (RCT) Comparing Two Intensive Speech Treatments (LSVT LOUD vs. LSVT ARTIC).

The majority of people with Parkinson's disease (PD) experience both prosodic changes (reduced vocal volume, reduced pitch range) and articulatory changes (imprecise articulation) that often limit speech intelligibility and may contribute to significant declines in quality of life. We conducted a randomized control trial comparing two intensive treatments, voice (LSVT LOUD) or articulation (LSVT ARTIC) to assess single word intelligibility in the presence of background noise (babble and mall). Participants (64 PD and 20 Healthy) read words from the diagnostic rhyme test (DRT), an ANSI Standard for measuring intelligibility of speech, before and after one month (treatment or no treatment). Teams of trained listeners blindly rated the data. Speech intelligibility of words in the presence of both noise conditions improved in PD participants who had LSVT LOUD compared to the groups that had LSVT ARTIC or no treatment. Intensive speech treatment targeting prominent prosodic variables in LSVT LOUD had a positive effect on speech intelligibility at the single word level in PD.

Doxorubicin-Induced Fetal Mesangial Cell Death Occurs Independently of TRPC6 Channel Upregulation but Involves Mitochondrial Generation of Reactive Oxygen Species.

Doxorubicin (DOX), a category D pregnancy drug, is a chemotherapeutic agent that has been shown in animal studies to induce fetal toxicity, including renal abnormalities. Upregulation of the transient receptor potential cation (TRPC) 6 channel is involved in DOX-induced podocyte apoptosis. We have previously reported that TRPC6-mediated Ca2+ signaling promotes neonatal glomerular mesangial cell (GMC) death. However, it is unknown whether DOX alters mesangial TRPC expression or viability in the fetus. In this study, cell growth was tracked in control and DOX-treated primary GMCs derived from fetal pigs. Live-cell imaging demonstrated that exposure to DOX inhibited the proliferation of fetal pig GMCs and induced cell death. DOX did not alter the TRPC3 expression levels. By contrast, TRPC6 protein expression in the cells was markedly reduced by DOX. DOX treatment also attenuated the TRPC6-mediated intracellular Ca2+ elevation. DOX stimulated mitochondrial reactive oxygen species (mtROS) generation and mitophagy by the GMCs. The DOX-induced mtROS generation and apoptosis were reversed by the mitochondria-targeted antioxidant mitoquinone. These data suggest that DOX-induced fetal pig GMC apoptosis is independent of TRPC6 channel upregulation but requires mtROS production. The mtROS-dependent GMC death may contribute to DOX-induced fetal nephrotoxicity when administered prenatally.

Structural brain abnormalities associated with cognitive impairments in bipolar disorder.

OBJECTIVE: Cognitive impairment has been highlighted as a core feature of bipolar disorder (BD) that often persists during remission. The specific brain correlates of cognitive impairment in BD remain unclear which impedes efficient therapeutic approaches. In a large sample of remitted BD patients, we investigated whether morphological brain abnormalities within dorsal prefrontal cortex (PFC) and hippocampus were related to cognitive deficits. METHODS: Remitted BD patients (n = 153) and healthy controls (n = 52) underwent neuropsychological assessment and structural MRI. Based on hierarchical cluster analysis of neuropsychological test performance, patients were classified as either cognitively impaired (n = 91) or cognitively normal (n = 62). The neurocognitive subgroups were compared amongst each other and with healthy controls in terms of dorsal PFC cortical thickness and volume, hippocampus shape and volume, and total cerebral grey and white matter volumes. RESULTS: Cognitively impaired patients displayed greater left dorsomedial prefrontal thickness compared to cognitively normal patients and healthy controls. Hippocampal grey matter volume and shape were similar across patient subgroups and healthy controls. At a whole-brain level, cognitively impaired patients had lower cerebral white matter volume compared to the other groups. Across all participants, lower white matter volume correlated with more impaired neuropsychological test performance. CONCLUSIONS: Our findings associate cognitive impairment in bipolar disorder with cerebral white matter deficits, factors which may relate to the observed morphological changes in dorsomedial PFC possibly due to increased neurocognitive effort to maintain symptom stability in these remitted patients.

Perceptions of Racially and Ethnically Diverse Women at High Risk of Breast Cancer Regarding the Use of a Web-Based Decision Aid for Chemoprevention: Qualitative Study Nested Within a Randomized Controlled Trial.

BACKGROUND: Chemopreventive agents such as selective estrogen receptor modulators and aromatase inhibitors have proven efficacy in reducing breast cancer risk by 41% to 79% in high-risk women. Women at high risk of developing breast cancer face the complex decision of whether to take selective estrogen receptor modulators or aromatase inhibitors for breast cancer chemoprevention. RealRisks is a patient-centered, web-based decision aid (DA) designed to promote the understanding of breast cancer risk and to engage diverse women in planning a preference-sensitive course of decision making about taking chemoprevention. OBJECTIVE: This study aims to understand the perceptions of women at high risk of developing breast cancer regarding their experience with using RealRisks-a DA designed to promote the uptake of breast cancer chemoprevention-and to understand their information needs. METHODS: We completed enrollment to a randomized controlled trial among 300 racially and ethnically diverse women at high risk of breast cancer who were assigned to standard educational materials alone or such materials in combination with RealRisks. We conducted semistructured interviews with a subset of 21 high-risk women enrolled in the intervention arm of the randomized controlled trial who initially accessed the tool (on average, 1 year earlier) to understand how they interacted with the tool. All interviews were audio recorded, transcribed verbatim, and compared with digital audio recordings to ensure the accuracy of the content. We used content analysis to generate themes. RESULTS: The mean age of the 21 participants was 58.5 (SD 10.1) years. The participants were 5% (1/21) Asian, 24% (5/21) Black or African American, and 71% (15/21) White; 10% (2/21) of participants were Hispanic or Latina. All participants reported using RealRisks after being granted access to the DA. In total, 4 overarching themes emerged from the qualitative analyses: the acceptability of the intervention, specifically endorsed elements of the DA, recommendations for improvements, and information needs. All women found RealRisks to be acceptable and considered it to be helpful (21/21, 100%). Most women (13/21, 62%) reported that RealRisks was easy to navigate, user-friendly, and easily accessible on the web. The majority of women (18/21, 86%) felt that RealRisks improved their knowledge about breast cancer risk and chemoprevention options and that RealRisks informed their (17/21, 81%) decision about whether or not to take chemoprevention. Some women (9/21, 43%) shared recommendations for improvements, as they wanted more tailoring based on user characteristics, felt that the DA was targeting a narrow population of Hispanic or Latina by using graphic novel-style narratives, wanted more understandable terminology, and felt that the tool placed a strong emphasis on chemoprevention drugs. CONCLUSIONS: This qualitative study demonstrated the acceptability of the RealRisks web-based DA among a diverse group of high-risk women, who provided some recommendations for improvement.

Transoral incisionless fundoplication demonstrates durability at up to 9 years.

GOALS: To assess the long-term results of transoral incisionless fundoplication (TIF 2). BACKGROUND: TIF with the EsophyX2 is an accepted procedure to treat gastroesophageal reflux disease (GERD). Long-term data have been limited. We report clinical outcomes of 151 patients followed up to 9 years. STUDY: A single institution prospective registry of patients undergoing TIF 2 between 11/2008 and 7/2015. Outcomes were assessed by complications, re-interventions, and a mixed effect model of clinical response over time. RESULTS: A total of 151 patients (87 women), mean age 62 years (30-91), mean body mass index (BMI) 26.6 (20-36.1), 93% on daily proton pump inhibitor (PPI), underwent TIF 2 without hiatal hernia repair; 131 of the 151 patients (86%) were available for follow-up at a median of 4.92 years (0.7-9.7 years). Of 120 patients ⩾5 years post-TIF, 62 (51%) were followed for a median 6.8 years. Median GERD-health-related quality of life (HRQL) scores decreased from 21 (interquartile range (IQR) 9.5-30) off PPI and 14 (4-24) on PPI at baseline to 4 (2-8) at 4.92 years and remained at 5 (2-9) in the 62 patients 5-9 years post-TIF. Sixty-four per cent had successful (>50%) reductions in GERD-HRQL scores at 4.92 years and 68% of patients followed ⩾5 years. Median regurgitation decreased from 15 (8-20) off PPI and 11 (5-20) on PPI at baseline to 0 (0-4) at 4.92 years, remaining at 1 (0-3) in 62 patients 5-9 years post-TIF. Mixed model analyses confirmed significant and stable improvements in GERD-HRQL and regurgitation scores at all annual follow-up time points after TIF. Daily PPI use decreased from 93% to 32% at 4.92, and 22% at ⩾5 years post-TIF. Revision to laparoscopic fundoplication in 33(22%) showed comparable outcomes. Two patients recovered uneventfully after laparoscopic surgery for localized perforation. CONCLUSIONS: TIF 2 provides durable relief of GERD symptoms at up to 9 years with 69-80% of patients having a successful outcome by symptom response and PPI use.

Provider participation in the Florida Medicaid Promoting Interoperability program: Practice characteristics, meaning use attestations, and incentive payments.

OBJECTIVE: The objective of this study was to quantify the rate of provider participation beyond year 1 incentive in the Florida Medicaid Promoting Interoperability (PI) program, formerly the Electronic Health Record Incentive program, and identify the provider and practice characteristics associated with Meaningful Use attestations. METHODS AND MATERIALS: We conducted a retrospective cohort study using the 2011-2018 records from the PI program, Provider Participation Database. Bivariate associations between Meaningful Use and categorical and ordinal variables were tested using Chi-square and Mantel-Haenszel Chi-square, respectively, with results informing logistic regressions. Adjusted odds ratios and 95 % confidence intervals are reported. RESULTS: We found that 42.56 % of Florida Medicaid providers achieved Meaningful Use after receiving first-year incentives. Logistic regression showed that pediatricians represented the largest percentage of providers who achieved Meaningful Use (65.06 %) while dentists had the lowest Meaningful Use (7.78 %). We also found that certain geographic areas and various EHR vendors were associated with higher rates of providers Meaningful Use attestation. DISCUSSION: Although the PI program successfully influenced the adoption of a basic EHR system, low Meaningful Use attestations have inadvertently created a digital "advanced use" divide among providers who serve large numbers of Medicaid patients. This is concerning because advanced EHR functions are necessary precursors to address unmet socioeconomic needs to reduce health disparities. CONCLUSION: Florida has distributed over $100 million to Medicaid providers who ultimately did not achieve Meaningful Use after collecting their first-year incentive. Policy interventions that can promote advanced EHR use functions are necessary to optimize technology in low-resourced practice settings where the potential benefits are greater.

Intranasal oxytocin versus placebo for hyperphagia and repetitive behaviors in children with Prader-Willi Syndrome: A randomized controlled pilot trial.

OBJECTIVE: The effects of intranasal oxytocin and placebo on hyperphagia and repetitive behaviors were compared in children and adolescents with Prader Willi Syndrome (PWS). METHODS: Children and adolescents with PWS were enrolled in an 8-week double-blind placebo-controlled intranasal oxytocin randomized trial. Twenty-three (23) subjects were assigned to oxytocin (N = 11) or placebo (N = 12). Hyperphagia was measured with the Hyperphagia Questionnaire (HQ), and repetitive behavior was measured with Repetitive Behavior Scale- Revised (RBS-R). RESULTS: There were modest significant treatment by-time interactions indicating reduction in hyperphagia and repetitive behaviors across time for placebo but no reduction for oxytocin. Total HQ score showed a greater average reduction of 1.81 points/week for the placebo group vs. oxytocin, with maximum reduction at week 4. There were also greater reductions on HQ-Drive and HQ-Behavior subscales on placebo vs. oxytocin. RBS-R subscales followed similar patterns to the HQ, with a significantly greater reduction in sameness subscale behaviors (average 0.825 points/week) in the placebo group compared to the oxytocin group. Oxytocin was well tolerated, and the only adverse event that was both more common and possibly related to oxytocin vs. placebo was nocturia (n = 1 vs 0). CONCLUSION: Placebo was associated with modest improvement in hyperphagia and repetitive behaviors in childhood PWS whereas intranasal oxytocin was not associated with improvement in these domains. More work is needed to understand the meaning and mechanism of these findings on hyperphagia and repetitive behaviors in PWS.

A Decade of mTBI Experience: What Have We Learned? A Summary of Proceedings From a NATO Lecture Series on Military mTBI.

Mild traumatic brain injury (mTBI, also known as a concussion) as a consequence of battlefield blast exposure or blunt force trauma has been of increasing concern to militaries during recent conflicts. This concern is due to the frequency of exposure to improvised explosive devices for forces engaged in operations both in Iraq and Afghanistan coupled with the recognition that mTBI may go unreported or undetected. Blasts can lead to mTBI through a variety of mechanisms. Debate continues as to whether exposure to a primary blast wave alone is sufficient to create brain injury in humans, and if so, exactly how this occurs with an intact skull. Resources dedicated to research in this area have also varied substantially among contributing NATO countries. Most of the research has been conducted in the US, focused on addressing uncertainties in management practices. Development of objective diagnostic tests should be a top priority to facilitate both diagnosis and prognosis, thereby improving management. It is expected that blast exposure and blunt force trauma to the head will continue to be a potential source of injury during future conflicts. An improved understanding of the effects of blast exposure will better enable military medical providers to manage mTBI cases and develop optimal protective measures. Without the immediate pressures that come with a high operational tempo, the time is right to look back at lessons learned, make full use of available data, and modify mitigation strategies with both available evidence and new evidence as it comes to light. Toward that end, leveraging our cooperation with the civilian medical community is critical because the military experience over the past 10 years has led to a renewed interest in many similar issues pertaining to mTBI in the civilian world. Such cross-fertilization of knowledge will undoubtedly benefit all. This paper highlights similarities and differences in approach to mTBI patient care in NATO and partner countries and provides a summary of and lessons learned from a NATO lecture series on the topic of mTBI, demonstrating utility of having patients present their experiences to a medical audience, linking practical clinical care to policy approaches.

Microbial biomarkers reveal a hydrothermally active landscape at Olduvai Gorge at the dawn of the Acheulean, 1.7 Ma.

Landscape-scale reconstructions of ancient environments within the cradle of humanity may reveal insights into the relationship between early hominins and the changing resources around them. Many studies of Olduvai Gorge during Pliocene-Pleistocene times have revealed the presence of precession-driven wet-dry cycles atop a general aridification trend, though may underestimate the impact of local-scale conditions on early hominins, who likely experienced a varied and more dynamic landscape. Fossil lipid biomarkers from ancient plants and microbes encode information about their surroundings via their molecular structures and composition, and thus can shed light on past environments. Here, we employ fossil lipid biomarkers to study the paleolandscape at Olduvai Gorge at the emergence of the Acheulean technology, 1.7 Ma, through the Lower Augitic Sandstones layer. In the context of the expansion of savanna grasslands, our results represent a resource-rich mosaic ecosystem populated by groundwater-fed rivers, aquatic plants, angiosperm shrublands, and edible plants. Evidence of a geothermally active landscape is reported via an unusual biomarker distribution consistent with the presence of hydrothermal features seen today at Yellowstone National Park. The study of hydrothermalism in ancient settings and its impact on hominin evolution has not been addressed before, although the association of thermal springs in the proximity of archaeological sites documented here can also be found at other localities. The hydrothermal features and resources present at Olduvai Gorge may have allowed early hominins to thermally process edible plants and meat, supporting the possibility of a prefire stage of human evolution.

Organic matter from the Chicxulub crater exacerbated the K-Pg impact winter.

An asteroid impact in the Yucatán Peninsula set off a sequence of events that led to the Cretaceous-Paleogene (K-Pg) mass extinction of 76% species, including the nonavian dinosaurs. The impact hit a carbonate platform and released sulfate aerosols and dust into Earth's upper atmosphere, which cooled and darkened the planet-a scenario known as an impact winter. Organic burn markers are observed in K-Pg boundary records globally, but their source is debated. If some were derived from sedimentary carbon, and not solely wildfires, it implies soot from the target rock also contributed to the impact winter. Characteristics of polycyclic aromatic hydrocarbons (PAHs) in the Chicxulub crater sediments and at two deep ocean sites indicate a fossil carbon source that experienced rapid heating, consistent with organic matter ejected during the formation of the crater. Furthermore, PAH size distributions proximal and distal to the crater indicate the ejected carbon was dispersed globally by atmospheric processes. Molecular and charcoal evidence indicates wildfires were also present but more delayed and protracted and likely played a less acute role in biotic extinctions than previously suggested. Based on stratigraphy near the crater, between 7.5 × 1014 and 2.5 × 1015 g of black carbon was released from the target and ejected into the atmosphere, where it circulated the globe within a few hours. This carbon, together with sulfate aerosols and dust, initiated an impact winter and global darkening that curtailed photosynthesis and is widely considered to have caused the K-Pg mass extinction.

The effects of intensive speech treatment on intelligibility in Parkinson's disease: A randomised controlled trial.

BACKGROUND: More than 6,000,000 individuals worldwide are diagnosed with Parkinson's disease (PD). Nearly 90% develop speech signs that may substantially impair their speech intelligibility, resulting in losses in their communication and quality of life. Benefits of intensive speech treatment have been documented for a range of speech signs. However, the critical question of whether speech is more intelligible after treatment has not been investigated in a randomised controlled trial (RCT). We hypothesised that intensive speech treatment would improve speech intelligibility in PD. METHOD: Sixty-four patients with hypokinetic dysarthria secondary to PD participated in this single-centre, parallel arm, statistically-powered RCT. Reporting follows CONSORT guidelines for non-pharmacological treatment. Patients were recruited from US clinics and randomised using a statistician-derived minimisation algorithm, to intensive speech treatment (16 1-hour sessions/1 month) targeting voice (voice group) or targeting articulation (articulation group) or to an untreated group (no treatment group). Speech treatments were delivered by speech clinicians who specialised in treating patients with PD. Trial design minimised bias and supported equipoise. For intelligibility assessment, blinded listeners (n = 117) orthographically transcribed 57 patients' recorded, self-generated narrative speech samples, randomly presented in multi-talker babble noise. Listeners were American-English speakers, ages 18-35 years, with normal hearing. The primary outcome was baseline (pre-treatment) to post-treatment change in transcription accuracy (TA), recognised as the most objective measure of intelligibility. TA was defined as the percentage of words transcribed correctly. Listeners, data collectors, and data managers were blinded to treatment conditions and groups. Reliability was evaluated using intraclass correlation coefficients and differences amongst groups were evaluated by mixed-effects models, in accordance with the intention-to-treat approach.This trial was registered with ClinicalTrials.gov Identifier: NCT00123084. FINDINGS: Between June 23, 2016 and August 14, 2017, blinded listeners transcribed baseline and post-treatment speech samples for intelligibility assessment of 57 patients in the voice (n = 19), articulation (n = 19) and no treatment (n = 19) groups. Between-group differences (d) in changes from baseline to post-treatment in TA indicated significantly greater increases following treatment targeting voice than treatment targeting articulation (d = 26·2%, 95% CI 1·5 - 51·0; p = 0·04; ES=1·0). Differences between TA changes in the treatment targeting voice and in the no treatment group were significant (d = 42·8%, 95% CI 22·4 - 63·2; p = 0·0002; ES=1·8). Differences between TA changes in the treatment targeting articulation and in the no treatment group were not significant (d = 16·5%, 95% CI -6·1 - 39·2; p = 0·147; ES=0·9). INTERPRETATION: These findings provide the first RCT evidence that intensive speech treatment targeting voice improves speech intelligibility in PD. Thus, this evidence-based treatment may positively impact health-related quality of life for patients with PD globally when it is included in patient management.

Dexmedetomidine Provides Fewer Respiratory Events Compared With Propofol and Fentanyl During Third Molar Surgery: A Randomized Clinical Trial.

PURPOSE: Propofol and fentanyl can cause airway obstruction and respiratory depression when used together for intravenous sedation. This study investigated whether dexmedetomidine and midazolam would decrease respiratory events requiring intervention during deep sedation compared with propofol, fentanyl, and midazolam. PATIENTS AND METHODS: A prospective, randomized, double-blinded, controlled trial was designed to assess 2 intravenous treatment groups during third molar surgery. Patients were randomized into 2 groups. The control group (group P) received 0.8 µg/kg of fentanyl followed by propofol infusion at 125 µg/kg per minute over a 10-minute period with intraoperative boluses of 0.1 µg/kg. The study group (group D) received dexmedetomidine bolus infusion of 1 µg/kg over a 10-minute period followed by maintenance infusion at 0.5 µg/kg per hour. Both groups were given 0.03 mg/kg of midazolam before infusion. Scorers, masked to group, viewed the procedure remotely and evaluated the primary outcome variable of respiratory events requiring intervention. Secondary outcome variables evaluated by the scorers included the Behavioral Pain Scale for non-intubated patients at initial injection, cooperation score at 5 and 15 minutes, and time to ambulation and discharge. Patient satisfaction and hemodynamic stability were measured. The difference between groups regarding the occurrence of respiratory events was tested using the Fisher exact test, and mixed-effects models were used to compare repeated vital signs. RESULTS: The sample was composed of 141 patients randomly assigned to either group P (n = 67) or group D (n = 74). No statistically significant differences in the distribution of study variables were found between groups at baseline. A statistically significant difference in respiratory events requiring deliberate intervention existed between group P (25.4%) and group D (2.7%) (P < .0001). No statistically significant difference was found between groups for Behavioral Pain Scale score, cooperation score, time to ambulation or discharge, and patient satisfaction. CONCLUSIONS: Using dexmedetomidine and midazolam for outpatient surgery resulted in fewer respiratory events requiring deliberate intervention compared with propofol, fentanyl, and midazolam. Ambulation and discharge times were not prolonged using dexmedetomidine.