Imaging trapped quantum gases by off-axis holography.

We present a dispersive imaging method for trapped quantum gases based on digital off-axis holography. Both phase delay and intensity of the probe field are determined from the same image. Due to the heterodyne gain inherent to the holographic method, it is possible to retrieve the phase delay induced by the atoms at probe beam doses two orders of magnitude lower than phase-contrast imaging methods. Using the full field of the probe beam, we numerically correct for image defocusing.

A qualitative study of the feasibility and acceptability of a smoking cessation program for people living with HIV and emotional dysregulation.

Despite high rates of co-occurring tobacco use and anxiety among persons living with HIV, evidence-based interventions for these individuals are limited. An existing cognitive-behavioral treatment protocol for smoking cessation and anxiety (Norton, P. J., & Barrera, T. L. (2012). Transdiagnostic versus diagnosis-specific CBT for anxiety disorders: A preliminary randomized controlled noninferiority trial. Depression and Anxiety, 29(10), 874-882. https://doi.org/10.1002/da.21974) was modified to address transdiagnostic constructs, such as anxiety sensitivity, distress tolerance, and depressive symptomatology (Labbe, A. K., Wilner, J. G., Kosiba, J. D., Gonzalez, A., Smits, J. A., Zvolensky, M. J., … O'Cleirigh, C. (2017). Demonstration of an Integrated Treatment for Smoking Cessation and Anxiety Symptoms in People with HIV: A Clinical Case Study. Cognitive and Behavioral Practice, 24(2), 200-214. https://doi.org/10.1016/j.cbpra.2016.03.009). This study examines the feasibility and acceptability of the intervention as determined from qualitative data from structured exit interviews from 10 participants who completed treatment. Results demonstrated that participants were very motivated to quit smoking and enrolled in the program for health-related reasons and to be able to quit. Participants found nearly all the treatment components to be useful for reaching their smoking cessation goal and in managing emotional dysregulation. Last, all participants stated that they would strongly recommend the treatment program. This qualitative study provides initial evidence for the feasibility and acceptability of a modified smoking cessation treatment protocol for HIV+ individuals with anxiety and emotional dysregulation. Future research will focus on evaluating the efficacy of the protocol in a full-scale randomized controlled trial, as well as working to collect qualitative data from participants who discontinue treatment to better understand reasons for treatment attrition.

Changes in thyroid function of nestling tree swallows (Tachycineta bicolor) in relation to polycyclic aromatic compounds and other environmental stressors in the Athabasca Oil Sands Region.

In the Canadian Athabasca Oil Sands Region (AOSR), nestling tree swallows (Tachycineta bicolor) raised near mining-related activities accumulated greater concentrations of polycyclic aromatic compounds (PACs) that contributed to their poorer condition, growth, and reproductive success. Here, we report changes in thyroid function of the same 14 day old (do) nestlings (N ≤ 68) at these mining-related sites (OS1, OS2) compared to reference nestlings (REF1), and in relation to multiple environmental stressors that influence avian thyroid function. Thyroid function was compromised for OS1 nestlings but generally comparable between OS2 and REF1 chicks. In 2012, circulating total triiodothyronine (TT3) and thyroxine (TT4) were similar among all nestlings. The OS1 chicks had more active thyroid glands based on histological endpoints. Hepatic T4 outer-ring deiodinase (T4-ORD) activity was suppressed in OS1 and OS2 chicks. Despite inter-annual differences, OS1 chicks continued experiencing compromised thyroid function with significantly higher circulating TT4 and more active thyroid glands in 2013. The OS2 chicks had less active thyroid glands, which conceivably contributed to their suppressed growth (previously reported) relative to the heavier OS1 nestlings with more active thyroid glands. Thyroid gland activity was more influenced by the chicks' accumulation of (muscle), than exposure (feces) to naphthalene, C2-naphthalenes, and C1-fluorenes. Of four major volatile organic contaminants, sulfur dioxide (SO2) primarily influenced thyroid gland activity and structure, supporting previous findings with captive birds. When collectively considering environmental-thyroidal stressors, chicks had a greater thyroidal response when they experienced colder temperatures, accumulated more C2-naphthalenes, and consumed aquatic-emerging insects with higher PAC burdens than terrestrial insects (carbon (δ13C)). We hypothesize that the more active thyroid glands and higher circulating TT4 of the OS1 chicks supported their growth and survival despite having the highest PAC burdens, whereas the lack of thyroid response in the OS2 chicks combined with high PAC burdens, contributed to their smaller size, poorer condition and poorer survival.

Observation of a Space-Time Crystal in a Superfluid Quantum Gas.

Time crystals are a phase of matter, for which the discrete time symmetry of the driving Hamiltonian is spontaneously broken. The breaking of discrete time symmetry has been observed in several experiments in driven spin systems. Here, we show the observation of a space-time crystal using ultracold atoms, where the periodic structure in both space and time is directly visible in the experimental images. The underlying physics in our superfluid can be described ab initio and allows for a clear identification of the mechanism that causes the spontaneous symmetry breaking. Our results pave the way for the usage of space-time crystals for the discovery of novel nonequilibrium phases of matter.

Introduction of the lung allocation score in Germany.

The aim of this study was to assess performance of the new lung allocation system in Germany based on lung allocation score (LAS). Retrospective analysis of waitlist (WL) outflow, lung transplantation (LTx) activity and 3-month outcomes comparing 1-year pre- and post-LAS introduction on December 10, 2011 was performed. Following LAS introduction, WL registrations remained constant, while WL mortality fell by 23% (p = 0.04). Reductions in WL mortality occurred in patients with cystic fibrosis (CF; -52%), emphysema (chronic obstructive pulmonary disease [COPD]; -49%) and pulmonary hypertension (PH; -67%), but not idiopathic pulmonary fibrosis (IPF; +48%). LTx activity increased by 9% (p = 0.146). Compared to pre-LAS, more patients with IPF (32% vs. 29%) and CF (20% vs. 18%) underwent transplantation and comparatively fewer with COPD (30% vs. 39%). Median LAS among transplant recipients was highest in PH (53) and IPF (49) and lowest in COPD (34). Transplantation under invasive respiratory support increased to 13% (in CF 28%, +85%, p = 0.017). Three-month survival remained unchanged (pre: 96.1% and post: 94.9%, p = 0.94). Following LAS implementation in Germany, reductions in waiting list size and WL mortality were observed. Composition of transplant recipients changed, with fewer COPD and more IPF recipients. Transplantation under invasive respiratory support increased. Reductions in WL mortality were most pronounced among CF and PH patients.

Stable nitrogen isotopes of nestling tree swallows indicate exposure to different types of oil sands reclamation.

Tree swallows (Tachycineta bicolor) inhabiting reclaimed wetlands on the oil sands in northern Alberta are potentially exposed to elevated levels of oil sands constituents such as polycyclic aromatic compounds (PAC) through diet. While increased detoxification enzyme activity as measured using 7-ethoxyresorufin O-deethylase in nestlings is a generally accepted indicator of exposure to oil sands constituents, there is no apparent method to detect dietary exposure specific to oil sands processed material (OSPM). In this study, stable C and N isotopes were analyzed from muscle and feathers of nestling tree swallows (15 d old) to distinguish dietary exposure of birds near reference and OSPM wetlands. High δ¹5N and low δ¹³C values in the nestling tissues differentiated those from the OSPM wetlands and reference sites. Lower δ¹5N values of nestlings compared to the δ¹5N values of larval chironomids from an earlier study suggested that the majority of the diet of the nestlings was derived from non-OSPM sources, despite residence near and on the OSPM wetlands. Our finding of limited utilization of OSPM resources by tree swallows indicates either low abundance or diversity of dietary items emerging from OSPM wetlands, or sensory avoidance of prey from those wetlands. Minimal consumption of OSPM-derived dietary sources may be attributed to published findings of limited adverse effects on tree swallow reproduction, or growth and development for these same nestlings. This study demonstrated that stable isotope analysis, particularly for N isotopes, may serve as a useful tool to trace dietary exposure to OSPM constituents as part of avian ecotoxicology assessments of reclaimed wetlands on the oil sands.

Electrical Impedance Spectroscopy Quantifies Skin Barrier Function in Organotypic In Vitro Epidermis Models.

3 D human epidermal equivalents (HEEs) are a state-of-the-art organotypic culture model in pre-clinical investigative dermatology and regulatory toxicology. Here, we investigated the utility of electrical impedance spectroscopy (EIS) for non-invasive measurement of HEE epidermal barrier function. Our setup comprised a custom-made lid fit with 12 electrode pairs aligned on the standard 24-transwell cell culture system. Serial EIS measurements for seven consecutive days did not impact epidermal morphology and readouts showed comparable trends to HEEs measured only once. We determined two frequency ranges in the resulting impedance spectra: a lower frequency range termed EISdiff correlated with keratinocyte terminal differentiation independent of epidermal thickness and a higher frequency range termed EISSC correlated with stratum corneum thickness. HEEs generated from CRISPR/Cas9 engineered keratinocytes that lack key differentiation genes FLG, TFAP2A, AHR or CLDN1 confirmed that keratinocyte terminal differentiation is the major parameter defining EISdiff. Exposure to pro-inflammatory psoriasis- or atopic dermatitis-associated cytokine cocktails lowered the expression of keratinocyte differentiation markers and reduced EISdiff. This cytokine-associated decrease in EISdiff was normalized after stimulation with therapeutic molecules. In conclusion, EIS provides a non-invasive system to consecutively and quantitatively assess HEE barrier function and to sensitively and objectively measure barrier development, defects and repair.

Food web structure in oil sands reclaimed wetlands.

Boreal wetlands play an important role in global carbon balance. However, their ecosystem function is threatened by direct anthropogenic disturbance and climate change. Oil sands surface mining in the boreal regions of Western Canada denudes tracts of land of organic materials, leaves large areas in need of reclamation, and generates considerable quantities of extraction process-affected materials. Knowledge and validation of reclamation techniques that lead to self-sustaining wetlands has lagged behind development of protocols for reclaiming terrestrial systems. It is important to know whether wetlands reclaimed with oil sands process materials can be restored to levels equivalent to their original ecosystem function. We approached this question by assessing carbon flows and food web structure in naturally formed and oil sands-affected wetlands constructed in 1970-2004 in the postmining landscape. We evaluated whether a prescribed reclamation strategy, involving organic matter amendment, accelerated reclaimed wetland development, leading to wetlands that were more similar to their natural marsh counterparts than wetlands that were not supplemented with organic matter. We measured compartment standing stocks for bacterioplankton, microbial biofilm, macrophytes, detritus, and zoobenthos; concentrations of dissolved organic carbon and residual naphthenic acids; and microbial production, gas fluxes, and aquatic-terrestrial exports (i.e., aquatic insect emergence). The total biomass of several biotic compartments differed significantly between oil sands and reference wetlands. Submerged macrophyte biomass, macroinvertebrate trophic diversity, and predator biomass and richness were lower in oil sands-affected wetlands than in reference wetlands. There was insufficient evidence to conclude that wetland age and wetland amendment with peat-mineral mix mitigate effects of oil sands waste materials on the fully aquatic biota. Although high variability was observed within most compartments, our data show that 20-year-old wetlands containing oil sands material have not yet reached the same level of function as their reference counterparts.

Pathology of enteric infections induced by the acanthocephalan Profilicollis chasmagnathi in Olrog's gull, Larus atlanticus, from Argentina.

Acanthocephalans can be pathogenic helminths of marine birds. Every year during the breeding season, there is variable mortality among prefledged chicks from the largest known Olrog's gull (Larus atlanticus) colony. Mortality has been associated with infection by the acanthocephalan Profilicollis chasmagnathi. Our aim was to study the role of chicks' size as a risk factor for intensity of infection and severe pathology, and to expand upon previous pathological findings reported in acanthocephalan-infected chicks. Size of the chick was associated with intensity of infection and number of intestinal perforations, which increased by 6.9% and 4.1%, respectively, for each millimetre increment in chick size. Infection was associated with inflammatory enteritis and granulomatous peritonitis. Complete intestinal perforations were observed in 85% and 97.3% of the studied chicks in 2005 and 2006, respectively, and they were observed very early during the post-hatching period. Our results show: (1) the presence of advanced pathology associated with acanthocephalan infections in chicks, beginning very early in the post-hatching period; and (2) significant increases in the intensity of infection and the associated pathology as a function of size of chicks, in dead chicks during this period.

Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation.

Static cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.

The influence of laboratory-induced MELD score differences on liver allocation: more reality than myth.

BACKGROUND: Liver allocation in Eurotransplant (ET) is based on the MELD score. Interlaboratory MELD score differences in INR and creatinine determination have been reported. The clinical implication of this observation has not been demonstrated. METHODS: MELD scores were calculated in 66 patients with liver cirrhosis using bilirubin, creatinine, and INR analyzed in six liver transplant centers. Based on allocation results of ET, patients transplanted from December 2006 to June 2007 were divided according to MELD score in four groups. For each group, the influence of the match MELD on the probability of receiving a transplant was studied (Cox proportional hazards model). RESULTS: Laboratory-dependent significant differences in MELD score were demonstrated. Cox proportional hazards model showed a significant association between MELD score and the probability of organ allocation. The unadjusted hazard ratio for receiving a liver transplant was significantly different between group 2 and group 4 (group 2: MELD 19-24; group 4: MELD > 30). CONCLUSION: Laboratory-dependent significant differences in MELD score were observed between the six transplant centers. We demonstrated a significant association between the MELD score and the probability of organ allocation. The observed interlaboratory variation might yield a significant difference in organ allocation in patients with high MELD scores.

The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys.

Vascular renal resistance (RR) during hypothermic machine perfusion (HMP) is frequently used in kidney graft quality assessment. However, the association between RR and outcome has never been prospectively validated. Prospectively collected RR values of 302 machine-perfused deceased donor kidneys of all types (standard and extended criteria donor kidneys and kidneys donated after cardiac death), transplanted without prior knowledge of these RR values, were studied. In this cohort, we determined the association between RR and delayed graft function (DGF) and 1-year graft survival. The RR (mmHg/mL/min) at the end of HMP was an independent risk factor for DGF (odds ratio 38.1 [1.56-934]; p = 0.026) [corrected] but the predictive value of RR was low, reflected by a c-statistic of the receiver operator characteristic curve of 0.58. The RR was also found to be an independent risk factor for 1-year graft failure (hazard ratio 12.33 [1.11-136.85]; p = 0.004). Determinants of transplant outcome are multifactorial in nature and this study identifies RR as an additional parameter to take into account when evaluating graft quality and estimating the likelihood of successful outcome. However, RR as a stand-alone quality assessment tool cannot be used to predict outcome with sufficient precision.

Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart.

We report a novel real-time imaging model to visualize apoptotic membrane changes of single cardiomyocytes in the injured heart of the living mouse, using fluorescent labeled annexin-V. Annexin-V binds to externalized phosphatidylserine (PS) of cells undergoing programmed cell death. With high-magnification (x100-160) real-time imaging, we visualized the binding of annexin-V to single cardiomyocytes. Kinetic studies at the single-cell level revealed that cardiomyocytes started to bind annexin-V within minutes after reperfusion, following an ischemic period of 30 minutes. The amount of bound annexin-V increased rapidly and reached a maximum within 20-25 minutes. Caspase inhibitors decreased the number of annexin-V-positive cardiomyocytes and slowed down the rate of PS exposure of cardiomyocytes that still bound annexin-V. This technology to study cell biology in the natural environment will enhance knowledge of intracellular signaling pathways relevant for cell-death regulation and strategies to manipulate these pathways for therapeutic effect.

A homologue of Drosophila tissue polarity gene frizzled is expressed in migrating myofibroblasts in the infarcted rat heart.

Myocardial infarction results in the formation of granulation tissue in the injured ventricular wall. This tissue contains myofibroblasts in highly organized arrays; their contractile properties may help to prevent the infarct area from dilatation. The mechanisms that control myofibroblast alignment are unknown. We found that myofibroblasts express a homologue of Drosophila tissue polarity gene frizzled (fz2) when migrating into the granulation tissue. The expression is decreased after the cells have aligned. This suggests that fz2 is involved in the spatial control of cardiac wound repair after infarction, possibly through intra- and intercellular transmission of polarity signals as in developing Drosophila. Mutations in the fz2 gene may impair myofibroblast alignment in the infarct area, thereby resulting in ventricular dilatation and aneurism following infarction.

Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome.

Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action potential at low heart rates predisposes individuals with LQT3 to fatal arrhythmias, typically at rest or during sleep. Here we report that mice heterozygous for a knock-in KPQ-deletion (SCN5A(Delta/+)) show the essential LQT3 features and spontaneously develop life-threatening polymorphous ventricular arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats caused lengthening of the action potential with early afterdepolarization and triggered arrhythmias in Scn5a(Delta/+) mice. Adrenergic agonists normalized the response to rate acceleration in vitro and suppressed arrhythmias upon premature stimulation in vivo. These results show the possible risk of sudden heart-rate accelerations. The Scn5a(Delta/+) mouse with its predisposition for pacing-induced arrhythmia might be useful for the development of new treatments for the LQT3 syndrome.

Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure.

Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA-/- mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.

Subchronic lead exposure, immunotoxicology and increased disease resistance in Japanese quail (Corturnix coturnix japonica).

The present study investigated the effects of lead (Pb) on immune responses in quail (Coturnix coturnix japonica) and the pathological impact of exposure to an infectious agent (E. coli O2). Fifty-four, 4-week-old quail were exposed to lead acetate in drinking water at 5 or 50 ppm. All birds were vaccinated with Newcastle Vaccine (NDV) during the third week of contaminant (Pb) exposure. In the fourth week, several arms of the immune response were tested using the T cell based phytohemagglutinin (PHA) skin test, the B cell mediated antibody response to NVD, and the chemiluminescence assay measuring innate immunity. Immunohistochemistry (IHC) was used to determine the expression of toll like receptor-3 (TLR-3) in the bursa of Fabricius. In the fifth week, quail were challenged with 200 µL of E. coli O2 (1×10(4) colony forming units (CFU)/mL). No clinical signs of Pb toxicity were observed. Morbidity/mortality subsequent to E. coli exposure was lowest in the high exposure group (27.8%) compared to low exposure (44.4%) and control (55.5%) groups. There was no difference in the T-cell-mediated PHA response, primary or secondary immune response or the innate response in Pb exposed groups; however, bursal TLR-3 increased (p<0.05) with higher Pb exposure. No evidence supported that subchronic Pb exposure was immunotoxic to quail at 5 or 50 ppm in drinking water. In contrast, our results provide evidence of a hormetic effect, with Pb exposed birds having lower morbidity and better survival than controls. Subchronic Pb exposure may be immunostimulatory rather than suppressive as predicted in earlier studies based on testing individual immune parameters.

Immunotoxicity and disease resistance in Japanese quail (Corturnix coturnix japonica) exposed to malathion.

The purpose of this study was to evaluate the impact of malathion on the immune system of wild birds, using Japanese quail (Coturnix coturnix japonica) as a model. Quail were exposed to malathion in drinking water at environmentally realistic concentrations (0 ppm, 1 ppm, and 10 ppm). In the fifth week, several arms of the immune response were tested using the T-cell based phytohemagglutinin (PHA) skin test, the B-cell mediated antibody response, and the chemiluminescence assay measuring innate immunity. After the sixth week of malathion exposure, quail were challenged with E. coli O2. The bursa of Fabricius and the spleen were assessed for histopathology. No clinical signs of malathion toxicity were observed. Morbidity or mortality subsequent to E. coli exposure tended (P = 0.08) to be higher in the high exposure group (50.0%) compared to the control (22.2%) group. There was no difference in the innate immune response in the malathion exposed birds, however, humoral immunity was suppressed (P = 0.03) with the higher malathion exposure. Histopathological evaluation revealed an immunosuppressive effect of malathion on the bursa of Fabricius; bursal atrophy, decreased B-cell density and increased apoptosis in the medulla, and increased connective tissue thickness of the follicular epithelium. Antibody suppression was correlated with bursal changes and peripheral blood lymphocyte count, the organ and cells involved in antibody production. Following the same pattern as other immunotoxicity tests, the PHA T-cell proliferative response also tended to be suppressed in the high exposure group. This study provides evidence that subchronic, moderate malathion exposure is immunotoxic to quail and that testing integrated, functional immunity using an infectious challenge is a better predictor of immunotoxicity than individual responses to immunotoxicity tests. The secondary antibody response, circulating lymphocyte populations, and bursal histopathology were the most sensitive indicators of immune status, as these predicted decreased disease resistance with malathion exposure.

Contralateral hearing loss in children with a unilateral enlarged vestibular aqueduct.

OBJECTIVE: To evaluate the long-term ipsi- and contralateral hearing of patients with a unilateral enlarged vestibular aqueduct (EVA). STUDY DESIGN: Multicenter retrospective cohort study. SETTING: Three tertiary otology and audiology referral centers. PATIENTS AND DIAGNOSTIC INTERVENTIONS: A total of 34 children with a unilateral enlarged vestibular aqueduct as identified on CT and/or MR imaging were evaluated with pure tone and speech perception audiometry. MEAN OUTCOME MEASURES: Radiologic measurements of the vestibular aqueduct, ipsi- and contralateral hearing loss, ipsi- and contralateral hearing loss progression over time and DNA test results. RESULTS: All patients in this cohort with unilateral EVA presented with hearing loss. Hearing loss was progressive in 38% of the ipsilateral ears. In 29% of the children, hearing loss was also found in the contralateral ear without EVA. In 90%, the contralateral hearing was stable, with a mean follow up of 4.2 years. We found a significant correlation between the severity of the hearing loss and the size of the EVA. A genetic diagnosis associated with EVA and/or SNHL was found in only 7%. CONCLUSION: About a third of the children with unilateral EVA are at risk of developing hearing loss in the contralateral ear. This indicates that at least in some patients with a unilateral EVA, a bilateral pathogenic process underlies the hearing loss, in contrary to what the imaging results suggest. These findings are important for counseling of EVA patients and their parents and have implications for follow up.