Paddlebots: Translation of Rotating Colloidal Assemblies near an Air/Water Interface.

Microbot propulsion requires unique strategies due to the dominance of viscosity and the reversible nature of microscale flows. To address this, swimmers of specific structure that translate in bulk fluid are commonly used; however, another approach is to take advantage of the inherent asymmetry of liquid/solid surfaces for microbots (µbots) to walk or roll. Using this technique, we have previously demonstrated that superparamagnetic colloidal particles can be assembled into small µbots, which can quickly roll along solid surfaces. In an analogous approach, here we show that symmetry can be similarly broken near air/liquid interfaces and µbots propelled at rates comparable to those demonstrated for liquid/solid interfaces.

Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6-deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

Fast In Situ Observation of Atomic Feshbach Resonances by Photoassociative Ionization.

We propose and experimentally investigate a scheme for observing Feshbach resonances in atomic quantum gases in situ and with a high temporal resolution of several tens of nanoseconds. The method is based on the detection of molecular ions, which are optically generated from atom pairs at small interatomic distances. As a test system we use a standard rubidium gas (^{87}Rb) with well known magnetically tunable Feshbach resonances. The fast speed and the high sensitivity of our detection scheme allows us to observe a complete Feshbach resonance within one millisecond and without destroying the gas.

Supersolid Properties of a Bose-Einstein Condensate in a Ring Resonator.

We investigate the dynamics of a Bose-Einstein condensate interacting with two noninterfering and counterpropagating modes of a ring resonator. Superfluid, supersolid, and dynamic phases are identified experimentally and theoretically. The supersolid phase is obtained for sufficiently equal pump strengths for the two modes. In this regime we observe the emergence of a steady state with crystalline order, which spontaneously breaks the continuous translational symmetry of the system. The supersolidity of this state is demonstrated by the conservation of global phase coherence at the superfluid to supersolid phase transition. Above a critical pump asymmetry the system evolves into a dynamic runaway instability commonly known as collective atomic recoil lasing. We present a phase diagram and characterize the individual phases by comparing theoretical predictions with experimental observations.

Three-dimensional docking of alcohols to ketones: an experimental benchmark based on acetophenone solvation energy balances.

The two hydrogen bond solvation sites exhibited by the carbonyl group in acetophenone are influenced by alkylation of the methyl group in both the acetophenone and in the prototype solvent methanol, largely due to London dispersion forces. Phenyl docking and alkyl docking preferences can be realized at will by appropriate substitution. In particular, cyclopropylation helps to stabilize the opposite phenyl docking site. In all cases, the energy gap is small enough to allow for a simultaneous detection even under low temperature conditions. This density functional prediction is checked experimentally by jet FTIR spectroscopy and largely confirmed. A spurious out-of-plane solvation preference predicted for cyclopropylphenylketone with tert-butyl alcohol by B3LYP-D3 calculations is not confirmed experimentally. It is unlikely that this discrepancy is due to zero-point energy effects. Instead, the second most stable alkyl-side solvation motif predicted with a more in-plane coordination is found in the jet expansion. Overall, the ability of carbonyl solvation balances to benchmark subtle electronic structure effects for non-covalent interactions without major nuclear motion corrections is supported.

Pinning Transition of Bose-Einstein Condensates in Optical Ring Resonators.

We experimentally investigate the dynamic instability of Bose-Einstein condensates in an optical ring resonator that is asymmetrically pumped in both directions. We find that, beyond a critical resonator-pump detuning, the system becomes stable regardless of the pump strength. Phase diagrams and quenching curves are presented and described by numerical simulations. We discuss a physical explanation based on a geometric interpretation of the underlying nonlinear equations of motion.

Observation of Subradiant Atomic Momentum States with Bose-Einstein Condensates in a Recoil Resolving Optical Ring Resonator.

We experimentally investigate the formation of subradiant atomic momentum states in Bose-Einstein condensates inside a recoil resolving optical ring resonator according to the theoretical proposal of Cola, Bigerni, and Piovella. The atoms are pumped from the side with laser light that contains two frequency components. They resonantly drive cavity assisted Raman transitions between three discreet atomic momentum states. Within a few hundred microseconds, the system evolves into a stationary subradiant state. In this state, the condensate develops two density gratings suitable to diffract the two frequency components of the pump field into the resonator. Both components destructively interfere such that scattering is efficiently suppressed. A series of subradiant states for various amplitude ratios of the two pump components between 0 and 2.1 have been observed. The results are well explained with a three state quantum model in mean field approximation.

Impact of early palliative care on caregivers of patients with advanced cancer: cluster randomised trial.

Background: Early palliative care improves the quality of life (QoL) and satisfaction with care of patients with advanced cancer, but little is known about its effect on caregivers. Here, we report outcomes of caregiver satisfaction with care and QoL from a trial of early palliative care. Patients and methods: Twenty-four medical oncology clinics were cluster-randomised, stratified by tumour site (lung, gastrointestinal, genitourinary, breast and gynaecological), to early palliative care team referral, or to standard oncology care with palliative care only as needed. Caregivers of patients with advanced cancer (clinical prognosis of 6-24 months, Eastern Cooperative Oncology Group 0-2) in both trial arms completed validated measures assessing satisfaction with care (FAMCARE-19) and QoL [SF-36v2 Health Survey; Caregiver QoL-Cancer (CQoL-C)], at baseline and monthly for 4 months. We used a multilevel linear random-intercept mixed-effect model to test whether there was improvement in the intervention group relative to the control group over 3 and 4 months. Results: A total of 182 caregivers completed baseline measures (94 intervention, 88 control); 151 caregivers (77 intervention, 74 control) completed at least one follow-up assessment. Satisfaction with care improved in the palliative intervention group compared with controls over 3 months (P = 0.007) and 4 months (P = 0.02). There was no significant improvement in the intervention group compared with controls for CQoL-C (3 months: P = 0.92, 4 months: P = 0.51), Physical Component Summary of the SF-36v2 Health Survey (3 months: P = 0.83, 4 months: P = 0.20), or Mental Component Summary of the SF-36v2 Health Survey (3 months: P = 0.87, 4 months: P = 0.60). Conclusion: Early palliative care increased satisfaction with care in caregivers of patients with advanced cancer. ClinicalTrials.gov identifier: NCT01248624.

Preliminary psychometrics of the Existential Distress Scale in patients with advanced cancer.

Existential distress is of clinical concern in patients with terminal illness. Although existential distress has been used to describe a broad spectrum of psychological disturbances, its narrower definition may be confined to distress that arises when the meaning and value of one's life is unclear, and is comorbid with feelings of loneliness and low self-worth. To promote further study, we developed and pilot-tested a 10-item Existential Distress Scale (EDS). Twenty-one patients with advanced cancer were recruited from a palliative care unit. Measures of existential distress, death anxiety, depression, performance status and physical symptom burden were collected. The EDS showed promising psychometric properties, including significant associations with death anxiety and depression. Thirty-eight per cent of the sample reported great or unbearable distress on at least one existential concern. The EDS may be administered to measure existential distress in patients with advanced cancer and clinicians may find the instrument useful to initiate a structured discussion about this symptom.

Canadian recommendations for the management of breakthrough cancer pain.

Breakthrough cancer pain (btcp) represents an important element in the spectrum of cancer pain management. Because most btcp episodes peak in intensity within a few minutes, speed of medication onset is crucial for proper control. In Canada, several current provincial guidelines for the management of cancer pain include a brief discussion about the treatment of btcp; however, there are no uniform national recommendations for the management of btcp. That lack, accompanied by unequal access to pain medication across the country, contributes to both regional and provincial variability in the management of btcp. Currently, immediate-release oral opioids are the treatment of choice for btcp. This approach might not always offer optimal speed for onset of action and duration to match the rapid nature of an episode of btcp. Novel transmucosal fentanyl formulations might be more appropriate for some types of btcp, but limited access to such drugs hinders their use. In addition, the recognition of btcp and its proper assessment, which are crucial steps toward appropriate treatment selection, remain challenging for many health care professionals. To facilitate appropriate management of btcp, a group of prominent Canadian specialists in palliative care, oncology, and anesthesiology convened to develop a set of recommendations and suggestions to assist Canadian health care providers in the treatment of btcp and the alleviation of the suffering and discomfort experienced by adult cancer patients.

Efimov Resonance and Three-Body Parameter in a Lithium-Rubidium Mixture.

We study collisional heating in a cold ^{7}Li-^{87}Rb mixture near a broad Feshbach resonance at 661 G. At the high field slope of the resonance, we find an enhanced three-body recombination rate that we interpret as a heteronuclear Efimov resonance. With improved Feshbach spectroscopy of two further resonances, a model for the molecular potentials has been developed that now consistently explains all known Feshbach resonances of the various Li-Rb isotope mixtures. The model is used to determine the scattering length of the observed Efimov state. Its value of -1870a_{0} Bohr radii supports the currently discussed assumption of universality of the three-body parameter also in heteronuclear mixtures.

Sensitivity of ultracold atoms to quantized flux in a superconducting ring.

We report on the magnetic trapping of an ultracold ensemble of (87)Rb atoms close to a superconducting ring prepared in different states of quantized magnetic flux. The niobium ring of 10 µm radius is prepared in a flux state n Φ(0), where Φ(0)=h/2e is the flux quantum and n varying between ±6. An atomic cloud of 250 nK temperature is positioned with a harmonic magnetic trapping potential at ∼18 µm distance below the ring. The inhomogeneous magnetic field of the supercurrent in the ring contributes to the magnetic trapping potential of the cloud. The induced deformation of the magnetic trap impacts the shape of the cloud, the number of trapped atoms, as well as the center-of-mass oscillation frequency of Bose-Einstein condensates. When the field applied during cooldown of the chip is varied, the change of these properties shows discrete steps that quantitatively match flux quantization.

Trypanocidal activity of free and nanoencapsulated curcumin on Trypanosoma evansi.

This study aimed to evaluate in vitro and in vivo trypanocidal activity of free and nanoencapsulated curcumin against Trypanosoma evansi. In vitro efficacy of free curcumin (CURC) and curcumin-loaded in lipid-core nanocapsules (C-LNCs) was evaluated to verify their lethal effect on T. evansi. To perform the in vivo tests, T. evansi-infected animals were treated with CURC (10 and 100 mg kg(-1), intraperitoneally [i.p.]) and C-LNCs (10 mg kg(-1), i.p.) during 6 days, with the results showing that these treatments significantly attenuated the parasitaemia. Infected untreated rats showed protein peroxidation and an increase of nitrites/nitrates, whereas animals treated with curcumin showed a reduction on these variables. As a result, the activity of antioxidant enzymes (superoxide dismutase and catalase) differs between groups (P<0.05). Infected animals and treated with CURC exhibited a reduction in the levels of alanine aminotransferase and creatinine, when compared with the positive control group. The use of curcumin in vitro resulted in a better parasitaemia control, an antioxidant activity and a protective effect on liver and kidney functions of T. evansi-infected adult male Wistar rats.

Bacteria and their cell wall components uniformly co-activate interleukin-17-producing thymocytes.

Interleukin (IL)-17-producing T cells play a critical role in the immune response against microbial pathogens. Traditionally, experimental studies have focused upon understanding the activity of IL-17-producing T cells which differentiate from naive T cells in the peripheral immune system. However, we have demonstrated previously that IL-17-producing T cells are also present in the thymus of naive wild-type mice and can be co-activated there by microbial stimuli. Other studies have supported the concept that IL-17-producing thymocytes have a specific role in the immediate defence against microbial pathogens, which is independent from the development of an adaptive immune response. Given an important role of the thymus in systemic bacterial infection and sepsis, in this study we investigate the effect of a broad spectrum of bacteria and cell wall components on thymocyte cytokine production. Surprisingly, we find that all types of bacteria investigated (including non-pathogenic species) uniformly activate IL-17-producing thymocytes upon α-CD3 stimulation. In contrast, there is a heterogeneous effect on IL-6 and interferon (IFN)-γ-production with Gram-negative bacteria inducing far higher frequencies of IL-6- and IFN-γ-producing thymocytes than Gram-positive bacteria. We conclude that IL-17-producing thymocytes constitute a 'first line of recognition', but not a 'first line of defence' against bacteria in general. Their activity might lead to immune activation, but not necessarily to a pathological inflammatory disease condition. The difference between these two states might be determined by other immunological effector molecules, such as IL-6 and IFN-γ.

Dynamical instability of a Bose-Einstein condensate in an optical ring resonator.

We experimentally investigate the dynamical instability of a Bose-Einstein condensate in an optical ring resonator for various cavity detuning and pump powers. The resulting stability diagram is asymmetric with respect to the cavity detuning and can be described by the coupling of two atomic modes with one optical mode. We compare the experimental data to a numerical simulation and to an analytic expression of the phase boundary. For positive and negative pump cavity detuning, different coupling mechanisms are identified explaining the asymmetry of the stability diagram. We present a physical interpretation and discuss the connection to the Dicke quantum phase transition.

T cell activation status determines the cytokine pattern induced by zymosan and bacterial DNA both in thymocytes and splenocytes.

Proinflammatory cytokines are essential mediators of the immunopathology associated with microbial sepsis. The fungal cell wall component zymosan and bacterial DNA are well-studied experimental tools for investigating these processes, simulating the presence of fungal or bacterial infection. Cells of the immune periphery, but also immune cells in the thymus, are affected essentially by the presence of microbes or their immune stimuli in sepsis. For this reason, we investigated the cytokine pattern present in the spleen (containing mature immune cells) and the thymus (containing immature immune cells) upon exposure to zymosan and Escherichia coli DNA. To study the role of T cell activation status, we investigated ex-vivo cultures with and without αCD3 stimulation for changes in their cytokine secretion pattern as measured by cytokine enzyme-linked immunospot (ELISPOT) and flow cytometry analysis. We found that both substances strongly co-stimulate αCD3-induced interferon (IFN)-γ and interleukin (IL)-6 secretion in the thymus and in the spleen, but stimulate IL-17 production only moderately. Moreover, zymosan increases PLP peptide (PLPp)-specific IFN-γ and IL-6 production in experimental autoimmune encephalomyelitis (EAE) induced in Swiss Jim Lambert (SJL)/J mice, confirming that T cell activation status is crucial for the cytokines secreted by an immune cell population encountering a microbial pathogen or immunostimulating parts of it.

The utility of the Edmonton Symptom Assessment System in screening for anxiety and depression.

The Edmonton Symptom Assessment System (ESAS) is a common screening tool in cancer, although its validity for distress screening is unproven. Here, screening performance of the ESAS anxiety (ESAS-A) and depression (ESAS-D) items were validated against the anxiety [Generalised Anxiety Disorder-7 (GAD-7)] and depression [Patient Health Questionnaire-9 (PHQ-9)] subscales of the PHQ. A total of 1215 cancer patients completed the Distress Assessment and Response Tool (DART), a computerised distress screening instrument. Spearman's rank correlation coefficients and receiver operating characteristic curve analyses were used to evaluate the ability of ESAS-A and ESAS-D to identify moderate distress (GAD-7/PHQ-9 ≥ 10). Spearman's rank correlation coefficients comparing ESAS-A and ESAS-D with GAD-7 and PHQ-9 were 0.74 and 0.72 respectively. Areas under the receiver operating characteristic curves were 0.89 and 0.88 for anxiety and depression respectively. A cut-off of ≥3 on ESAS-A demonstrated a sensitivity of 0.91, specificity of 0.68, positive predictive value of 0.34 and negative predictive value of 0.97. A cut-off of ≥2 on the ESAS-D demonstrated a sensitivity of 0.86, specificity of 0.72, positive predictive value of 0.46 and negative predictive value of 0.95. High sensitivities of ESAS-A and ESAS-D at certain cut-offs suggest they have use in ruling-out distress. However, their low specificities indicate secondary screening is needed to rule-in anxiety or depression for case-finding.

Multimodal microwheel swarms for targeting in three-dimensional networks.

Microscale bots intended for targeted drug delivery must move through three-dimensional (3D) environments that include bifurcations, inclined surfaces, and curvature. In previous studies, we have shown that magnetically actuated colloidal microwheels (µwheels) reversibly assembled from superparamagnetic beads can translate rapidly and be readily directed. Here we show that, at high concentrations, µwheels assemble into swarms that, depending on applied magnetic field actuation patterns, can be designed to transport cargo, climb steep inclines, spread over large areas, or provide mechanical action. We test the ability of these multimodal swarms to navigate through complex, inclined microenvironments by characterizing the translation and dispersion of individual µwheels and swarms of µwheels on steeply inclined and flat surfaces. Swarms are then studied within branching 3D vascular models with multiple turns where good targeting efficiencies are achieved over centimeter length scales. With this approach, we present a readily reconfigurable swarm platform capable of navigating through 3D microenvironments.