Josephson-like Tunnel Resonance and Large Coulomb Drag in GaAs-Based Electron-Hole Bilayers.

Bilayers consisting of two-dimensional (2D) electron and hole gases separated by a 10 nm thick AlGaAs barrier are formed by charge accumulation in epitaxially grown GaAs. Both vertical and lateral electric transport are measured in the millikelvin temperature range. The conductivity between the layers shows a sharp tunnel resonance at a density of 1.1×10^{10} cm^{-2}, which is consistent with a Josephson-like enhanced tunnel conductance. The tunnel resonance disappears with increasing densities and the two 2D charge gases start to show 2D-Fermi-gas behavior. Interlayer interactions persist causing a positive drag voltage that is very large at small densities. The transition from the Josephson-like tunnel resonance to the Fermi-gas behavior is interpreted as a phase transition from an exciton gas in the Bose-Einstein-condensate state to a degenerate electron-hole Fermi gas.

Scanning gradiometry with a single spin quantum magnetometer.

Quantum sensors based on spin defects in diamond have recently enabled detailed imaging of nanoscale magnetic patterns, such as chiral spin textures, two-dimensional ferromagnets, or superconducting vortices, based on a measurement of the static magnetic stray field. Here, we demonstrate a gradiometry technique that significantly enhances the measurement sensitivity of such static fields, leading to new opportunities in the imaging of weakly magnetic systems. Our method relies on the mechanical oscillation of a single nitrogen-vacancy center at the tip of a scanning diamond probe, which up-converts the local spatial gradients into ac magnetic fields enabling the use of sensitive ac quantum protocols. We show that gradiometry provides important advantages over static field imaging: (i) an order-of-magnitude better sensitivity, (ii) a more localized and sharper image, and (iii) a strong suppression of field drifts. We demonstrate the capabilities of gradiometry by imaging the nanotesla fields appearing above topographic defects and atomic steps in an antiferromagnet, direct currents in a graphene device, and para- and diamagnetic metals.

Efficacy of digital cognitive behavioural therapy for symptoms of generalised anxiety disorder: a study protocol for a randomised controlled trial.

BACKGROUND: Generalised anxiety disorder (GAD) is a chronic and disabling condition with considerable personal and economic impact. Cognitive behavioural therapy (CBT) is a recommended psychological therapy for GAD; however, there are substantial barriers to accessing treatment. Digital CBT, in particular smartphone-delivered CBT, has the potential to improve accessibility and increase dissemination of CBT. Despite the emerging evidence of smartphone-based psychological interventions for reducing anxiety, effect size scores are typically smaller than in-person interventions, and there is a lack of research assessing the efficacy of smartphone-delivered digital interventions specifically for GAD. METHODS: In the DeLTA trial (DigitaL Therapy for Anxiety), we plan to conduct a parallel-group superiority randomised controlled trial examining the efficacy of a novel smartphone-based digital CBT intervention for GAD compared to a waitlist control. We aim to recruit 242 adults (aged 18 years or above) with moderate-to-severe symptoms of GAD. This trial will be conducted entirely online and will involve assessments at baseline (week 0; immediately preceding randomisation), mid-intervention (week 3), post-intervention (week 6; primary end point) and follow-up (week 10). The primary objective is to evaluate the efficacy of the intervention on GAD symptom severity compared to a waitlist control at post-intervention. Secondary objectives are to examine between-group effects on GAD at follow-up, and to examine the following secondary outcomes at both post-intervention and follow-up: 1) worry; 2) depressive symptoms; 3) wellbeing; 4) quality of life; and 5) sleep difficulty. DISCUSSION: This trial will report findings on the initial efficacy of a novel digital CBT intervention for GAD. Results have the potential to contribute towards the evidence base for digital CBT for GAD and increase the dissemination of CBT. TRIAL REGISTRATION: ISRCTN, ISRCTN12765810. Registered on 11 January 2019.

Endogenous testosterone levels are predictive of symptom reduction with exposure therapy in social anxiety disorder.

The Hypothalamus-Pituitary-Gonadal (HPG)-axis, and testosterone in particular, play an important role in social motivational behavior. Socially avoidant behavior, characteristic of social anxiety disorder (SAD), has been linked to low endogenous testosterone levels, and can be alleviated by testosterone administration in SAD. Although these beneficial effects of testosterone may translate to exposure therapy, it remains unknown whether testosterone increases prior to exposure improve therapy outcomes. In this proof-of-principle study, we tested whether pre-exposure (reactive and baseline) endogenous testosterone levels were predictive of exposure outcome in SAD. Seventy-three participants (52 females) with a principal SAD diagnosis performed four speech exposures: three during one standardized exposure therapy session and one at post-assessment one week later. Subjective fear levels were assessed before and after each speech exposure and social anxiety symptoms were assessed at pre- and post-treatment. Pre-treatment testosterone levels were assessed before (baseline) and in response to a pre-exposure instruction session (reactive). Pre-treatment testosterone levels were not related to fear levels during exposure therapy, but predicted pre- to post-treatment reductions in social anxiety symptom severity. Specifically, low baseline and high reactive pre-treatment testosterone levels were associated with larger reductions in social anxiety symptom severity. These findings support the role of HPG-axis in social fear reduction. Specifically, our finding that high reactive testosterone as well as low baseline testosterone predicted exposure outcome in SAD, suggests that good reactivity of the HPG-axis is a promising marker for the symptom-reducing effects of exposure therapy.

A preliminary study of human model head and neck response to frontal loading in nontraditional occupant seating configurations.

OBJECTIVE: Computational human body models (HBMs) are nominally omnidirectional surrogates given their structural basis in human anatomy. As a result, such models are well suited for studies related to occupant safety in anticipated highly automated vehicles (HAVs). We utilize a well-validated HBM to study the head and neck kinematics in simulations of nontraditional occupant seating configurations. METHODS: The GHBMC M50-O v. 4.4 HBM was gravity settled into a generic seat buck and situated in a seated posture. The model was simulated in angular increments of 15 degrees clockwise from forward facing to rear facing. A pulse of 17.0 kph (NASS median) was used in each to simulate a frontal impact for each of the 13 seating configurations. Belt anchor points were rotated with the seat; the airbag was appropriately powered based on delta-V, and was not used in rear-facing orientations. Neck forces and moments were calculated. RESULTS: The 30-degree oblique case was found to result in the maximum neck load and sagittal moment, and thus Neck Injury Criteria (NIJ). Neck loads were minimized in the rear facing condition. The moments and loads, however, were greatest in the lateral seating configuration for these frontal crash simulations. CONCLUSIONS: In a recent policy statement on HAVs, the NHTSA indicated that vehicle manufacturers will be expected to provide countermeasures that will fully protect occupants given any planned seating or interior configurations. Furthermore, the agency indicated that virtual tests using human models could be used to demonstrate such efficacy. While the results presented are only appropriate for comparison within this study, they do indicate that human models provide reasonable biomechanical data for nontraditional occupant seating arrangements.

Multicentre derivation and validation of a simple predictive index for healthcare-associated Clostridium difficile infection.

OBJECTIVES: Clostridium difficile infection (CDI) is the most common cause of healthcare-associated infections in the United States. Despite well-established risk factors, little research has focused on use of these variables to identify a patient population at high risk for CDI to target with primary prevention strategies. A predictive index for healthcare-associated CDI could improve clinical care and guide research for primary prevention trials. Our objective was to develop a predictive index to identify patients at high risk for healthcare-associated CDI. METHODS: We performed a secondary database analysis in a five-hospital health system in Houston, Texas. Our cohort consisted of 97 130 hospitalized patients admitted for more than 48 hours between October 2014 and September 2016. The derivation cohort consisted of the initial 80% of admissions (75 545 patients), with the remainder being used in the validation cohort. RESULTS: CDI rates in the derivation and validation cohorts were 1.55% and 1.43%, respectively. Thirty-day predictors of CDI were increased number of high-risk antibiotics, Charlson comorbidity index score, age and receipt of a proton pump inhibitor. These variables were incorporated into a simple risk index with a score range of 0 to 10. The final model demonstrated good discrimination and calibration with the observed CDI incidence ranging from 0.1% to 20.4%. CONCLUSIONS: We developed a predictive index for 30-day risk of healthcare-associated CDI using readily available and clinically useful variables. This simple predictive risk index may be used to improve clinical decision making and resource allocation for CDI stewardship initiatives, and guide research design.

The Glaucous-Winged Gull (Larus glaucescens) as an Indicator of Chemical Contaminants in the Canadian Pacific Marine Environment: Evidence from Stable Isotopes.

The Glaucous-winged gull (Larus glaucescens) has been selected by Environment Canada as a marine indicator species for long-term monitoring of persistent contaminants in the Canadian Pacific. However, the indicator value of this species depends on its trophic level and proportion of marine prey in its diet. Eggs, used as the monitoring medium, are produced entirely from maternal resources and knowledge of adult diet before and during egg production is critical to interpreting contaminant levels. Due to a lack of recent and reliable dietary ecology work, we examined the diet of breeding Glaucous-winged gulls through carbon (δ13C) and nitrogen (δ15N) stable isotope analysis at three colonies on the Pacific coast. Near-shore marine prey, occupying a high trophic level (δ15N), composed a predominant component of all Glaucous-winged gull diet. Adult diet composition from colonies in the Salish Sea was more varied than the west coast of Vancouver Island, reflecting the opportunistic foraging nature of this species in areas where the abundance of marine prey is known to fluctuate. Compared with incubating adults, pre-laying adults had a significantly lower trophic level that may reflect the need to consume marine invertebrates to acquire specific nutrients necessary for egg production. Interannual variation in both trophic level and prey source (δ13C) in egg and chick tissues indicates the need to pair ongoing contaminant monitoring with stable isotope analysis. The predominantly marine diet and relatively high trophic level of this gull supports its use as an indicator of marine pollution on the Pacific coast.

Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients.

BACKGROUND: One of the proposed mechanisms of trastuzumab-induced regression of human epidermal growth factor receptor 2-positive (HER2+) tumours includes facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates ADCC. We presented our pilot study of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer. METHODS: Patients with HER2+ metastatic breast cancer that progressed after trastuzumab +/- chemotherapy were continued on trastuzumab 2 mg kg(-1) intravenous weekly and GM-CSF 250 µg m(-2) subcutaneous daily. Patients were assessed for response every 8 weeks. Treatment was continued until disease progression or intolerable toxicity. RESULTS: Seventeen patients were evaluable (median age 48 years, range 27-75 years). The median number of metastatic sites was 2 (range 1-3); the most common site was the liver (n=10). The median number of prior regimens for metastatic disease was 2 (range 1-5). No objective disease response was observed, but five patients (29%) had stable disease for a median duration of 15.8 (range 10-53.9) weeks. The most common adverse event was rash at the injection site. No grade 4 or irreversible adverse event was seen. CONCLUSION: The addition of GM-CSF to trastuzumab alone had a modest clinical benefit and acceptable safety profile in heavily pretreated patients with trastuzumab-resistant HER2+ metastatic breast cancer.

Prolonged disease control by nonmyeloablative allogeneic transplantation for metastatic breast cancer.

We found earlier that high-dose chemotherapy with Allo-SCT produced a tumor response in patients with chemorefractory metastatic breast cancer. In this study, we examined the efficacy and toxicity of nonmyeloablative allogeneic PBSC transplantation in patients with chemosensitive metastatic breast cancer. Twelve patients with metastatic breast carcinoma who had stable disease after standard-dose chemotherapy and six who had a partial response underwent allogeneic transplantation. The conditioning regimen consisted of reduced-intensity fludarabine and melphalan. All patients achieved engraftment and hematopoietic recovery. Nine patients developed grade II or higher acute GVHD; seven of these nine responded to immunosuppressive therapy. Fourteen patients developed chronic GVHD. The treatment-related mortality rate was 11%. With a median follow-up of 565 days, the median survival duration was 643 days and the median progression-free survival duration was 202 days. Two patients are alive with a complete response 1555 and 2526 days after SCT, and one patient is alive with progressive bone disease at day 1118. We conclude that among patients with chemotherapy-sensitive metastatic breast cancer, a fraction will achieve a durable complete response after SCT with a reduced-intensity conditioning regimen. The question remains how to improve the overall efficacy and reduce the mortality rate for this approach.

High-resolution comprehensive radiation hybrid maps of the porcine chromosomes 2p and 9p compared with the human chromosome 11.

We are constructing high-resolution, chromosomal 'test' maps for the entire pig genome using a 12,000-rad WG-RH panel (IMNpRH2(12,000-rad))to provide a scaffold for the rapid assembly of the porcine genome sequence. Here we present an initial, comparative map of human chromosome (HSA) 11 with pig chromosomes (SSC) 2p and 9p. Two sets of RH mapping vectors were used to construct the RH framework (FW) maps for SSC2p and SSC9p. One set of 590 markers, including 131 microsatellites (MSs), 364 genes/ESTs, and 95 BAC end sequences (BESs) was typed on the IMNpRH2(12,000-rad) panel. A second set of 271 markers (28 MSs, 138 genes/ESTs, and 105 BESs) was typed on the IMpRH(7,000-rad) panel. The two data sets were merged into a single data-set of 655 markers of which 206 markers were typed on both panels. Two large linkage groups of 72 and 194 markers were assigned to SSC2p, and two linkage groups of 84 and 168 markers to SSC9p at a two-point LOD score of 10. A total of 126 and 114 FW markers were ordered with a likelihood ratio of 1000:1 to the SSC2p and SSC9p RH(12,000-rad) FW maps, respectively, with an accumulated map distance of 4046.5 cR(12,000 )and 1355.2 cR(7,000 )for SSC2p, and 4244.1 cR(12,000) and 1802.5 cR(7,000) for SSC9p. The kb/cR ratio in the IMNpRH2(12,000-rad) FW maps was 15.8 for SSC2p, and 15.4 for SSC9p, while the ratio in the IMpRH(7,000-rad) FW maps was 47.1 and 36.3, respectively, or an approximately 3.0-fold increase in map resolution in the IMNpRH(12,000-rad) panel over the IMpRH(7,000-rad) panel. The integrated IMNpRH(12,000-rad) andIMpRH(7,000-rad) maps as well as the genetic and BAC FPC maps provide an inclusive comparative map between SSC2p, SSC9p and HSA11 to close potential gaps between contigs prior to sequencing, and to identify regions where potential problems may arise in sequence assembly.

Ionophore taste preferences of dairy heifers.

Two taste preference studies were conducted using six Holstein heifers in each experiment to determine preferences for no ionophore, lasalocid, or monensin in the diet. In Exp. 1, individually penned (approx. 5 mo old; 220 +/- 14 kg BW) heifers were fed a basal total mixed ration containing 46% corn silage, 46% grass haylage, and 8% soybean meal (DM basis). There were five treatments (mg/kg BW(-1)*d(-1)): 0 ionophore (control), 1 lasalocid (1L), 2 lasalocid (2L), 1 monensin (1M), or 2 monensin (2M). Ionophores were provided as part of the mineral mix that had been added to the control diet and through an ionophore-grain by-product mix to make the 2L and 2M treatments. All five diets were offered for 7 d, with the first 2 d for adaptation and the last 5 d for measurement of feed intake. The most preferred diet was then removed and the study continued with the four remaining diets. The most preferred diets were again eliminated sequentially, so that only two diets remained on d 13 and 14. Each feeding segment ranking of treatment preferences was determined based on the weight of feed refused at the end of each feeding segment. In Exp. 2, six 6-wk-old heifers (75 +/- 5 kg of BW) were individually fed either 0, 1L, or 1M in a study similar to Exp. 1, except that the most preferred diet was removed after 4 d, with the first day for adaptation and the last 3 d for measurement of feed intake. In Exp. 1, orthogonal contrasts indicated that heifers preferred the 1L and 2L diets over the 1M and 2M diets. Preferences between diet concentrations of ionophores (1 and 2 mg/kg of BW; Exp. 1) and the control and ionophore treatments did not differ, nor was there an interaction between ionophores and their concentration. Dairy heifers previously fed lasalocid prefer lasalocid over monensin when given a choice; however, heifers without previous exposure to an ionophore did not indicate a preference (Exp. 2).

A randomized phase II study of two schedules of bryostatin-1 (NSC339555) in patients with advanced malignant melanoma: A National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: This study addressed the efficacy and toxicity of the novel compound Bryostatin-1 (NSC 339555), a novel agent with antineoplastic, hematopoietic and immunomodulatory activity in a variety of in vitro and in vivo systems. PATIENTS AND METHODS: This phase II study randomly assigned chemotherapy-naïve patients with untreated metastatic melanoma and measurable disease to two schedules of treatment: Arm A, 25 microg/m2 bryostatin-1 given as a 24 hour continuous infusion weekly or Arm B, 120 microg/m2 bryostatin-1 given as a 72 hour continuous infusion every 2 weeks. Although objective response was assessed using standard NCIC CTG criteria, antitumour activity was assessed using a multivariate endpoint incorporating both response (CR and PR) and early progression (PD at < or = 8 weeks). Seventeen patients were randomized to each arm. RESULTS: Arm A was better tolerated with 86.7% of 15 evaluable patients receiving > or = 90% of planned dose intensity versus 76.5% of 17 evaluable patients in Arm B. On Arm B, three patients experienced serious adverse events and three patients had to be removed from protocol therapy due to toxicity. The most common side effect was myalgia (33% grade 1-2 on Arm A versus 65% on Arm B with 5 patients experiencing grade 3 and one patient grade 4). Lethargy was more common on Arm A but more severe on Arm B. Other side effects such as nausea, diarrhea and headache were generally mild to moderate in nature and occurred with a similar frequency on both arms. Hematologic and biochemical toxicity were minimal. This trial was closed early because the protocol-stopping rule was met based on lack of required responses and on the number of early progressions on both arms. No partial or complete responses were seen; 3 patients randomized to Arm A had stable disease (duration 9-24 weeks) as did 4 patients (duration 10-38 weeks) randomized to Arm B. CONCLUSION: Arm A was better tolerated than Arm B. We conclude that bryostatin-1 has little efficacy in the treatment of metastatic melanoma with either of the schedules studied.

Nitrogen deposition to and cycling in a deciduous forest.

The project described here seeks to answer questions regarding the role increased nitrogen (N) deposition is playing in enhanced carbon (C) sequestration in temperate mid-latitude forests, using detailed measurements from an AmeriFlux tower in southern Indiana (Morgan-Monroe State Forest, or MMSF). The measurements indicate an average atmosphere-surface N flux of approximately 6 mg-N m(-2) day(-1) during the 2000 growing season, with approximately 40% coming from dry deposition of ammonia (NH3), nitric acid (HNO3), and particle-bound N. Wet deposition and throughfall measurements indicate significant canopy uptake of N (particularly NH4+) at the site, leading to a net canopy exchange (NCE) of -6 kg-N ha(-1) for the growing season. These data are used in combination with data on the aboveground C:N ratio, litterfall flux, and soil net N mineralization rates to indicate the level of potential perturbation of C sequestration at this site.

Mothers with HIV/AIDS and their children: disclosure and guardianship issues.

For many mothers living with HIV/AIDS, whether, when, and how to disclose their HIV diagnosis to their children and arranging for future care are important although agonizing issues. Due to the increasing number of children who lose their mothers to AIDS and the dearth of empirical information about them, these issues are increasingly important to research. This study of 188 HIV-positive mothers and their 267 children of minor age in New York City revealed that only half the mothers had disclosed their HIV diagnosis to at least one of their children and only 57% had made formal plans for the children's care. As expected, older children were more likely to be informed than younger children. Contrary to some previous research, maternal disclosure was not related to ethnicity, advanced illness, improved psychological well-being, or greater or more satisfying social support resources. Implications for future research and provision of services to this group of women are discussed.

Self-injurious behavior and sleep disturbance in adults with developmental disabilities.

Sleep patterns of 30 individuals with self-injurious behavior and mental retardation were compared with those of 30 matched controls residing in the same residential facility that did not self-injure. Individuals were recorded as asleep or awake during 30 min intervals for eight hours per night. The results of a Wilcoxon signed-ranks test (p < .05) indicated that individuals with self-injury slept significantly less than individuals without self-injury. chi2 analyses (p < .01) indicated significantly greater variability in the number of intervals recorded as asleep among individuals with self-injury than their matched controls. These results are congruent with previous findings of sleep disturbance among persons with mental retardation and behavior problems. The possibility of neurochemical dysregulation in sleep disturbance among individuals with daytime self-injury is discussed.

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days-an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Sinusitis: bench to bedside. Current findings, future directions.

Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days--an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.