Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis.

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

Mapping the regulatory landscape of auditory hair cells from single-cell multi-omics data.

Auditory hair cells transduce sound to the brain, and in mammals, these cells reside together with supporting cells in the sensory epithelium of the cochlea, called the organ of Corti. To establish the organ's delicate function during development and differentiation, spatiotemporal gene expression is strictly controlled by chromatin accessibility and cell type-specific transcription factors, jointly representing the regulatory landscape. Bulk sequencing technology and cellular heterogeneity obscured investigations on the interplay between transcription factors and chromatin accessibility in inner ear development. To study the formation of the regulatory landscape in hair cells, we collected single-cell chromatin accessibility profiles accompanied by single-cell RNA data from genetically labeled murine hair cells and supporting cells after birth. Using an integrative approach, we predicted cell type-specific activating and repressing functions of developmental transcription factors. Furthermore, by integrating gene expression and chromatin accessibility data sets, we reconstructed gene regulatory networks. Then, using a comparative approach, 20 hair cell-specific activators and repressors, including putative downstream target genes, were identified. Clustering of target genes resolved groups of related transcription factors and was used to infer their developmental functions. Finally, the heterogeneity in the single-cell data allowed us to spatially reconstruct transcriptional as well as chromatin accessibility trajectories, indicating that gradual changes in the chromatin accessibility landscape are lagging behind the transcriptional identity of hair cells along the organ's longitudinal axis. Overall, this study provides a strategy to spatially reconstruct the formation of a lineage-specific regulatory landscape using a single-cell multi-omics approach.

Thirteen-Valent Pneumococcal Conjugate Vaccine-Induced Immunoglobulin G (IgG) Responses in Serum Associated With Serotype-Specific IgG in the Lung.

Pneumococcal conjugate vaccine (PCV) efficacy is lower for noninvasive pneumonia than invasive disease. In this study, participants were immunized with 13-valent PCV (PCV13) or hepatitis A vaccine (control). Bronchoalveolar lavage samples were taken between 2 and 6 months and serum at 4 and 7 weeks postvaccination. In the lung, anti-capsular immunoglobulin G (IgG) levels were higher in the PCV13 group compared to controls for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV13 group at 4 weeks for all serotypes, except serotype 3. IgG in bronchoalveolar lavage and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy. Clinical Trials Registration. ISRCTN 45340436.

Adolescent novelty seeking is associated with greater ventral striatal and prefrontal brain response during evaluation of risk and reward.

Adolescence is a period during which reward sensitivity is heightened. Studies suggest that there are individual differences in adolescent reward-seeking behavior, attributable to a variety of factors, including temperament. This study investigated the neurobiological underpinnings of risk and reward evaluation as they relate to self-reported pleasure derived from novel experiences on the revised Early Adolescent Temperament Questionnaire (EATQ-R). Healthy participants (N = 265, ~50% male), aged 12-17 years, underwent functional magnetic resonance imaging during a modified Wheel of Fortune task, where they evaluated choices with varying probability of winning different monetary rewards. Across all participants, there was increased brain response in salience, reward, and cognitive control circuitry when evaluating choices with larger (compared with moderate) difference in risk/reward. Whole brain and a priori region-of-interest regression analyses revealed that individuals reporting higher novelty seeking had greater activation in bilateral ventral striatum, left middle frontal gyrus, and bilateral posterior cingulate cortex when evaluating the choices for largest difference in risk/reward. These novelty seeking associations with brain response were seen in the absence of temperament-related differences in decision-making behavior. Thus, while heightened novelty seeking in adolescents might be associated with greater neural sensitivity to risk/reward, accompanying increased activation in cognitive control regions might regulate reward-driven risk-taking behavior. More research is needed to determine whether individual differences in brain activation associated with novelty seeking are related to decision making in more ecologically valid settings.

Developmental trajectories of Big Five personality traits among adolescents and young adults: Differences by sex, alcohol use, and marijuana use.

OBJECTIVE: Individual differences in adolescent personality are related to a variety of long-term health outcomes. While previous studies have demonstrated sex differences and non-linear changes in personality development, these results remain equivocal. The current study utilized longitudinal data (n = 831) from the National Consortium on Alcohol and Neurodevelopment in Adolescence to examine sex differences in the development of personality and the association between substance use and personality. METHOD: Participants (ages 12-21 at baseline) completed the Ten-Item Personality Inventory and self-reported past year alcohol and marijuana use at up to 7 yearly visits. Data were analyzed using generalized additive mixed-effects models and linear mixed-effects models. RESULTS: Findings support linear increases in agreeableness and conscientious and decreases in openness with age and inform on timing of sex-specific non-linear development of extraversion and emotional stability. Further, results provide novel information regarding the timing of the association between substance use and personality, and replicate past reporting of differential associations between alcohol and marijuana use and extraversion, and sex-dependent effects of marijuana use on emotional stability. CONCLUSIONS: These findings highlight the importance of modeling sex differences in personality development using flexible non-linear modeling strategies, and accounting for sex- and age-specific effects of alcohol and marijuana use.

Dielectric Measurement of Agricultural Grain Moisture-Theory and Applications.

Moisture content is a critical variable for the harvesting, processing, storing and marketing of cereal grains, oilseeds and legumes. Efficient and accurate determination of grain moisture content even with advanced nondestructive techniques, remains a challenge due to complex water-retaining biological structures and hierarchical composition and geometry of grains that affect measurement interpretation and require specific grain-dependent calibration. We review (1) the primary factors affecting permittivity measurements used in practice for inferring moisture content in grains; (2) develop novel methods for estimating critical parameters for permittivity modeling including packing density, porosity, water binding surface area and water phase permittivity and (3) represent the permittivity of packs of grains using dielectric mixture theory as a function of moisture content applied to high moisture corn (as a model grain). Grain permittivity measurements are affected by their free and bound water contents, chemical composition, temperature, constituent shape, phase configuration and measurement frequency. A large fraction of grain water is bound exhibiting reduced permittivity compared to that of free water. The reduced mixture permittivity and attributed to hydrophilic surfaces in starches, proteins and other high surface area grain constituents. The hierarchal grain structure (i.e., kernel, starch grain, lamella, molecule) and the different constituents influence permittivity measurements due to their layering, geometry (i.e., kernel or starch grain), configuration and water-binding surface area. Dielectric mixture theory offers a physically-based approach for modeling permittivity of agricultural grains and similar granular media.

Seasonal impoundment management reduces nitrogen cycling but not resilience to surface fire in a tidal wetland.

Hydrology and salinity regimes of many impounded wetlands are manipulated to provide seasonal habitats for migratory waterfowl, with little-known consequences for ecosystem structure and function. Managed hydrology can alter ecosystems by directly changing soil properties and processes and by influencing plant community dynamics. Additionally, management history may influence ecosystem response to disturbance, including fires. To better understand how wetland management regime influences ecosystem response to disturbance, we quantified elevation, soil nitrogen concentrations and process rates, and plant community structure and diversity in a natural experiment following the 2018 Branscombe Fire. We measured paired burned-unburned patches in both tidally-influenced and managed, seasonally-impounded wetlands in Suisun Marsh, California, USA. Unburned ecosystem structure and nutrient cycling differed by wetland management history; unburned impounded wetlands were ∼1 m lower in elevation and plant community composition was dominated by succulents whereas the unburned tidal wetland was dominated by graminoids. Unburned impounded wetland soil nitrogen cycling (potential nitrification and denitrification) rates were <28% of those measured in unburned tidal wetland soils and soil extractable nitrate, ammonium, and dissolved inorganic phosphorus concentrations were also substantially lower in unburned impounded than unburned tidal wetlands. Despite these differences in pre-disturbance (i.e., unburned) conditions, all soil processes recovered to baseline levels within 6 months after surface fire, and we found no evidence of plant community change 1 year after fire in either wetland management type. Overall, water management history exerted stronger control on ecosystem processes and structure than surface fire disturbance. Low extractable soil nitrate and potential denitrification rates may indicate limitation of soil nitrogen removal in impounded wetlands, with implications for downstream environmental quality and eutrophication across managed landscapes.

Analysis of Real-World Data to Investigate the Impact of Race and Ethnicity on Response to Programmed Cell Death-1 and Programmed Cell Death-Ligand 1 Inhibitors in Advanced Non-Small Cell Lung Cancers.

BACKGROUND: Racial disparities among clinical trial participants present a challenge to assess whether trial results can be generalized into patients representing diverse races and ethnicities. The objective of this study was to evaluate the impact of race and ethnicity on treatment response in patients with advanced non-small cell lung cancer (aNSCLC) treated with programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors through analysis of real-world data (RWD). MATERIALS AND METHODS: A retrospective cohort study of 11,138 patients with lung cancer treated at hospitals within the Mount Sinai Health System was performed. Patients with confirmed aNSCLC who received anti-PD-1/PD-L1 treatment were analyzed for clinical outcomes. Our cohort included 249 patients with aNSCLC who began nivolumab, pembrolizumab, or atezolizumab treatment between November 2014 and December 2018. Time-to-treatment discontinuation (TTD) and overall survival (OS) were the analyzed clinical endpoints. RESULTS: After a median follow-up of 14.8 months, median TTD was 7.8 months (95% confidence interval, 5.4-not estimable [NE]) in 75 African American patients versus 4.6 (2.4-7.2) in 110 White patients (hazard ratio [HR], 0.63). Median OS was not reached (18.4-NE) in African American patients versus 11.6 months (9.7-NE) in White patients (HR, 0.58). Multivariable Cox regression conducted with potential confounders confirmed longer TTD (adjusted HR, 0.65) and OS (adjusted HR, 0.60) in African American versus White patients. Similar real-world response rate (42.6% vs. 43.5%) and disease control rate (59.6% vs. 56.5%) were observed in the African American and White patient populations. Further investigation revealed the African American patient group had lower incidence (14.7%) of putative hyperprogressive diseases (HPD) upon anti-PD-1/PD-L1 treatment than the White patient group (24.5%). CONCLUSION: Analysis of RWD showed longer TTD and OS in African American patients with aNSCLC treated with anti-PD-1/PD-L1 inhibitors. Lower incidence of putative HPD is a possible reason for the favorable outcomes in this patient population. IMPLICATIONS FOR PRACTICE: There is a significant underrepresentation of minority patients in randomized clinical trials, and this study demonstrates that real-world data can be used to investigate the impact of race and ethnicity on treatment response. In retrospective analysis of patients with advanced non-small cell lung cancer treated with programmed cell death-1 or programmed cell death-ligand 1 inhibitors, African American patients had significantly longer time-to-treatment discontinuation and longer overall survival. Analysis of real-world data can yield clinical insights and establish a more complete picture of medical interventions in routine clinical practice.

Australian adolescent population norms for the child health utility index 9D-results from the young minds matter survey.

OBJECTIVE: Patient-reported outcomes of health-related quality-of-life (HRQoL) are important descriptors of population health. A recent Australian adolescent population survey provided a unique opportunity to derive preference-based HRQoL. METHODS: Data from 2967 adolescents aged 11-17 years were analysed. An interviewer-led parent/carer questionnaire was administered for demographic variables and mental disorders of adolescents during previous 12 months using the Diagnostic Interview Schedule for Children. A self-report survey was administered to derive HRQoL using the child health utility nine-dimensions instrument (CHU-9D). Weighted HRQoL was derived for several demographic groups, mental disorder diagnosis, and youth risk behaviours. RESULTS: The total population had a mean utility of 0.78 [standard deviation (SD): 0.20]. Males had a significantly higher mean utility (0.81, SD 0.18) than females (0.76, SD: 0.21) (Cohen's d = 0.23, p < 0.001), and utility decreased with age for both males and females (p < 0.001). Family type and some parent/carer variables were associated with significant lower HRQoL scores with small effect size. Youth risk behaviours were associated with reduced HRQoL with moderate effect sizes. Adolescents who self-harmed, had suicidal ideation, or had a mental disorder had significantly lower utilities scores with moderate to large effect sizes compared to those who did not have such conditions. CONCLUSIONS: This study has provided contemporary Australian population norms for HRQoL in adolescents that may be used as cross comparison between studies as well as indicators allowing estimation of population health (e.g. estimation of the burden of disease) and can be used to populate future economic models.

Lifetime Alcohol Use Influences the Association Between Future-Oriented Thought and White Matter Microstructure in Adolescents.

AIMS: Future orientation, or the ability to plan ahead and anticipate consequences, is a capacity that develops during adolescence, yet its underlying neurobiology is unknown. Previous independent reports suggest that reduced future orientation and altered white matter microstructure are associated with greater alcohol use in adolescents; however, these effects have not been studied in conjunction. This study investigated the association between future orientation and white matter microstructure as a function of lifetime alcohol use. METHODS: Seventy-seven adolescents (46 female; 15-21 years of age) underwent diffusion weighted imaging (DWI) and completed a fifteen-item Future Orientation Questionnaire. Regression analyses assessed the association between self-reported lifetime alcohol use and future orientation, and the association between future orientation and white matter microstructure, as a function of lifetime alcohol use. RESULTS: Adolescents with more lifetime alcohol use demonstrated lower future orientation. Voxel-wise DWI analyses revealed two regions, bilateral posterior corona radiata (PCR), where greater future orientation was associated with lower mean diffusivity in those with little or no history of alcohol use; however, this association was diminished with increasing rates of lifetime alcohol use. CONCLUSIONS: These findings replicate reports of reduced future orientation as a function of greater lifetime alcohol use and demonstrate an association between future orientation and white matter microstructure, in the PCR, a region containing afferent and efferent fibers connecting the cortex to the brain stem, which depends upon lifetime alcohol use. These findings provide novel information regarding the underlying neurobiology of future-oriented thought and how it relates to alcohol use.

Associations between nucleus accumbens structural connectivity, brain function, and initiation of binge drinking.

Adolescent alcohol use is associated with increased risk for alcohol use disorders later in life; therefore, identifying biomarkers for initiation of heavy alcohol use, such as individual differences in the development of white-matter microstructure, may inform prevention strategies that improve public health. This prospective cohort study included 40 adolescents, ages 14 and 15, without substantial history of alcohol or drug use at baseline. Fractional anisotropy (FA), an index of white-matter microstructure, was assessed in pathways connecting the nucleus accumbens (NAcc) to the rest of the brain using diffusion tensor imaging. Path analyses were conducted voxel-wise within these pathways to examine direct effects of premorbid FA on number of months between baseline assessment and the onset of binge drinking and indirect effects mediated by NAcc activation during decision making assessed using functional magnetic resonance imaging. Adolescents with lower premorbid accumbofrontal FA began binge drinking sooner, an effect which was mediated by greater NAcc activation during decision making involving greater levels of risk and reward (P < .05 corrected). An additional direct effect of FA on duration to onset of binge drinking was observed in white matter near the ventral pallidum, as adolescents with lower premorbid FA in this region began binge drinking sooner (P < .05 corrected). Findings suggest that delayed maturation of prefrontal white matter is associated with less top-down control over striatal sensitivity to reward. These factors, along with individual differences in white matter proximal to ventral pallidum, may represent premorbid risk factors for earlier initiation of heavy alcohol use.

Dielectric Spectroscopy and Application of Mixing Models Describing Dielectric Dispersion in Clay Minerals and Clayey Soils.

The number of sensors, ground-based and remote, exploiting the relationship between soil dielectric response and soil water content continues to grow. Empirical expressions for this relationship generally work well in coarse-textured soils but can break down for high-surface area and intricate materials such as clayey soils. Dielectric mixing models are helpful for exploring mechanisms and developing new understanding of the dielectric response in porous media that do not conform to a simple empirical approach, such as clayey soils. Here, we explore the dielectric response of clay minerals and clayey soils using the mixing model approach in the frequency domain. Our modeling focuses on the use of mixing models to explore geometrical effects. New spectroscopic data are presented for clay minerals (talc, kaolinite, illite and montmorillonite) and soils dominated by these clay minerals in the 1 MHz-6 GHz bandwidth. We also present a new typology for the way water is held in soils that we hope will act as a framework for furthering discussion on sensor design. We found that the frequency-domain response can be mostly accounted for by adjusting model structural parameters, which needs to be conducted to describe the Maxwell-Wagner (MW) relaxation effects. The work supports the importance of accounting for soil structural properties to understand and predict soil dielectric response and ultimately to find models that can describe the dielectric-water content relationship in fine-textured soils measured with sensors.

Global environmental changes impact soil hydraulic functions through biophysical feedbacks.

Although only representing 0.05% of global freshwater, or 0.001% of all global water, soil water supports all terrestrial biological life. Soil moisture behaviour in most models is constrained by hydraulic parameters that do not change. Here we argue that biological feedbacks from plants, macro-fauna and the microbiome influence soil structure, and thus the soil hydraulic parameters and the soil water content signals we observe. Incorporating biological feedbacks into soil hydrological models is therefore important for understanding environmental change and its impacts on ecosystems. We anticipate that environmental change will accelerate and modify soil hydraulic function. Increasingly, we understand the vital role that soil moisture exerts on the carbon cycle and other environmental threats such as heatwaves, droughts and floods, wildfires, regional precipitation patterns, disease regulation and infrastructure stability, in addition to agricultural production. Biological feedbacks may result in changes to soil hydraulic function that could be irreversible, resulting in alternative stable states (ASS) of soil moisture. To explore this, we need models that consider all the major feedbacks between soil properties and soil-plant-faunal-microbial-atmospheric processes, which is something we currently do not have. Therefore, a new direction is required to incorporate a dynamic description of soil structure and hydraulic property evolution into soil-plant-atmosphere, or land surface, models that consider feedbacks from land use and climate drivers of change, so as to better model ecosystem dynamics.

An economic evaluation of a telephone outcall intervention for informal carers of cancer patients in Australia: An assessment of costs and quality-adjusted-life-years.

OBJECTIVE: Carers of people with cancer provide uncompensated care that is often physically, emotionally, and financially demanding, which results in neglect of their own health. This study's objective was to conduct an economic evaluation following a randomised control trial (RCT) involving a proactive telephone outcall intervention aimed at improving health outcomes among carers of cancer patients. METHODS: The trial was a single-blind, multicentre, RCT conducted across four Australian health services, comprising three outcalls from trained Cancer Council 131120 (Cancer Council telephone and information support services) nurses compared with three phone call reminders of the availability of 131120 services (control group). Outcalls consisted of telephone contacts to the caregivers initiated by the Cancer Council nurses. The primary trial outcome was reduced carer burden. Health care resource use was measured using a resource use questionnaire (RUQ), and costs were presented in 2013 $(AUS). Quality-adjusted-life-years (QALYs) were also used as health outcomes. An incremental cost-effectiveness ratio (ICER) was calculated, with bootstrapping used to quantify sampling variability. A $50 000 per QALY-gained willingness-to-pay threshold was used. Sensitivity analyses were conducted. RESULTS: Results showed that the total mean QALYs-gained were higher (0.02 QALYs, P = 0.01) in the control group, and total mean costs were lower in the control group ($477, P < 0.001) over the trial duration. The intervention group was dominated by the control group. Results were robust to sensitivity analyses. CONCLUSIONS: Results suggest policy makers should not adopt this intervention into routine health care in its current form. Further research into the efficacy and cost-effectiveness of telephone-based interventions for carers is required.

Schmallenberg virus neutralising antibody responses in sheep.

BACKGROUND: Schmallenberg virus (SBV) is a midge borne virus of cattle and sheep. Infection is typically asymptomatic in adult sheep but fetal infection during pregnancy can result in abortion, stillbirth, neurological disorders and malformations of variable severity in newborn animals. It was first identified in Germany and the Netherlands in 2011 and then circulated throughout Europe in 2012 and 2013. Circulation in subsequent years was low or non-existent until summer and autumn 2016, leading to an increased incidence of deformed newborn lambs and calves in 2016-17. This study reports SBV circulation in October 2016 within a group of 24 ewes and 13 rams. The ewes were monitored at 3 times points over an 11 week period (September to December 2016). RESULTS: Most ewes displayed an increase in SBV VNT with antibody titre increases greater in older, previously exposed ewes. Two ewes had SBV RNA detectable by RT-qPCR, one on 30/09/16 and one on 04/11/16. Of these ewes, one had detectable serum SBV RNA (indicating viraemia) despite pre-existing antibody. The rams had been previously vaccinated with a commercial inactivated SBV vaccine, they showed minimal neutralising antibody titres against SBV 8 months post-vaccination and all displayed increased titre in October 2016. CONCLUSION: This data suggests that SBV circulated for a minimum period of 5 weeks in September to October 2016 in central England. Ewes previously exposed to virus showed an enhanced antibody response compared to naïve animals. Pre-existing antibody titre did not prevent re-infection in at least one animal, implying immunity to SBV upon natural exposure may not be life-long. In addition, data suggests that immunity provided by killed adjuvanted SBV vaccines only provides short term protection (< 8 months) from virus.

End-of-life care in an Australian acute hospital: a retrospective observational study.

BACKGROUND: There is a gap in knowledge about the kind and quality of care experienced by hospital patients at the end of their lives. AIMS: To document and compare the patterns in end-of-life care for patients dying across a range of different medical units in an acute care hospital. METHODS: A retrospective observational study of consecutive adult inpatient deaths between 1 July 2010 and 30 June 2014 in four different medical units of an Australian tertiary referral hospital was performed. Units were selected on the basis of highest inpatient death rates and included medical oncology, respiratory medicine, cardiology and gastroenterology/hepatology. RESULTS: Overall, 41% of patients died with active medical treatment plans, but significantly more respiratory and cardiology patients died with ongoing treatment (46 and 75% respectively) than medical oncology and gastroenterology patients (each 27%, P < 0.05). More medical oncology and gastroenterology patients were recognised as dying (92 and 88%) compared with 72% of respiratory and only 38% of cardiology patients (P < 0.001). Significantly, more medical oncology patients were referred to palliative care and received comfort care plans than all other patient groups. However, the rate of non-palliative interventions given in the final 48 h was not significantly different between all four groups. CONCLUSIONS: There were differences in managing the dying process between all disciplines. A possible solution to these discrepancies would be to create an integrated palliative care approach across the hospital. Improving and reducing interdisciplinary practice variations will allow more patients to have a high-quality and safe death in acute hospitals.

Posterior auricular muscle patch graft for exposed orbital implant.

The purpose of this article is to describe a surgical technique to repair an exposed orbital implant by posterior auricular muscle autograft. A retrospective review was conducted of four patients with an exposed orbital implant that were treated with a posterior auricular muscle graft. Four patients received posterior auricular muscle patch graft to the exposed orbital implant. The donor site healed with minimal scarring and remained well hidden. The graft incorporated fully into surrounding orbital tissue with no recurrent exposure at average of 13 month follow-up. The posterior auricular muscle autograft is a viable technique for repairing an exposed orbital implant.

First Zika-positive donations in the continental United States.

BACKGROUND: Zika virus (ZIKV) has spread in the Americas, including parts of the southern United States, and infection can be associated with serious complications, including congenital brain abnormalities. Probable transfusion transmission of ZIKV has been documented in Brazil. STUDY DESIGN AND METHODS: Preemptive testing of blood donations for ZIKV RNA was implemented in southern US states at risk of local transmission using a test approved under a Food and Drug Administration (FDA) investigational new drug application, cobas Zika. Screening was expanded after issuance of an updated FDA guidance. Donations reactive on initial screening were further tested by nucleic acid and antibody tests to determine the donor status. RESULTS: Of 358,786 donations from US states screened by individual donation testing, 23 were initially reactive on cobas Zika. Fourteen of these represented probable ZIKV infection based on reactivity on additional nucleic acid testing or anti-Zika immunoglobulin M. Ten of the 14 donors reported travel to an identified ZIKV-active area within 90 days before donation (median time from end of travel to donation, 25 days; range, 6-71 days). Three donors with travel history also had a potential sexual exposure. Only seven of the 14 donations with probable ZIKV infection were detectable upon 1:6 dilution to simulate minipool testing. The estimated specificity of the cobas Zika test was 99.997%. CONCLUSION: Screening of donations for ZIKV RNA can interdict ZIKV-infected donors. Donor risk factors include travel more than 4 weeks before donation and sexual exposure. Minipool screening would have detected only 50% of the RNA-positive donations.

Impact of a Novel Bioabsorbable Implant on Radiation Treatment Planning for Breast Cancer.

BACKGROUND: Techniques for accurately delineating the tumor bed after breast-conserving surgery (BCS) can be challenging. As a result, the accuracy, and efficiency of radiation treatment (RT) planning can be negatively impacted. Surgically placed clips or the post-surgical seroma are commonly used to determine target volume; however, these methods can lead to a high degree of uncertainty and variability. A novel 3-dimensional bioabsorbable marker was used during BCS and assessed for its impact on RT planning. METHODS: One hundred and ten implants were sutured to the margins of the tumor bed excision site in 108 patients undergoing BCS. Routine CT imaging of the breast tissue was performed for RT planning, and the marker was assessed for visibility and utility in target delineation. RT regimens, target volumes and associated treatment costs were analyzed. RESULTS: In all patients, the marker was easily visible and in 95.7 % of cases, it proved useful for RT planning. 36.8 % of patients received conventional whole breast irradiation plus boost, 56.6 % received hypo-fractionation plus boost, and 6.6 % received accelerated partial breast irradiation. A shift toward increased use of hypo-fractionated regimens was noted over the three year period of this study. There were no device-related complications or cancer recurrences in this group of patients. CONCLUSIONS: This study demonstrated the use of a novel 3-dimensional marker as a safe and effective method for delineating the tumor bed with a significant utility for RT planning. With routine use of the device, an increased use of hypofractionation with a resultant 25 % cost savings was noted.

What Is the Role of Elective Neck Dissection in the Treatment of Patients With Buccal Squamous Cell Carcinoma and Clinically Negative Neck Findings?

PURPOSE: Buccal squamous cell carcinoma (BSCC) is rare in the United States. Given its location, few anatomic barriers to its spread exist, and it has been found to have a high locoregional recurrence rate. The role of elective neck dissection (END) in the clinically negative neck (N0) is not clear. In the present study, we measured the effect of END on the locoregional and distant metastasis rates among patients with clinically N0 BSCC. MATERIALS AND METHODS: A retrospective cohort study was conducted. The sample included subjects diagnosed with BSCC. The primary predictor variable was END status (yes vs no). The primary outcome variable was locoregional recurrence. The secondary outcome variables were distant metastasis and the 2- and 5-year survival rates. Other variables collected included demographic data, initial operation, adjuvant therapy, pathologic data, and stage. Kaplan-Meier and Cox proportional hazards statistics were computed. RESULTS: The sample included 20 subjects with clinical N0 BSCC and a mean age of 67 years (range 42-88); 55% were men. The disease stage was T1 in 30%, T2 in 40%, T3 in 15%, and T4 in 15%. Fifteen subjects underwent END. Of the 5 who had not undergone END, all 5 (100%) had locoregional recurrence and 1 (20%) had metastasis. Of the 15 who had undergone END, 5 (33%) had locoregional recurrence and 1 (7%) had metastasis (P = .002). The 2- and 5-year survival rates for N0 patients without END was 80% and 40%, respectively, compared with 93% and 87% for those who had undergone END. CONCLUSIONS: END had a therapeutic role, resulting in a lower locoregional recurrence rate. Also, the 2- and 5-year survival rates were greater for those who had undergone END.