Auditory spatial cueing reduces neglect after right-hemispheric stroke: A proof of concept study.

Spatial neglect after right-hemispheric stroke, characterized by the failure to attend or respond to the contralesional space, is a strong negative outcome predictor. Neglect is a supramodal syndrome affecting not only the visual but also the auditory modality. Preliminary studies used this audio-visual cross-modal effect to show short-lasting effects on attention towards the neglected space. The aim of the present study was to introduce a new technique of auditory stimulation combining the unspecific effect of music (i.e., patients choose their preferred music) with the effects of auditory spatial cueing (i.e., the music is presented dynamically as moving from right to left). The effect of this new auditory stimulation technique was investigated in two proof-of-concept experiments using repeated-measures, cross-over designs including 21 patients with visual neglect after a first right-hemispheric stroke. In Experiment I (n = 9), neglect patients showed a significantly larger improvement in Letter Cancellation after listening to preferred music with than without auditory spatial cueing. After granting the feasibility of this new auditory stimulation technique, we investigated the long-term aftereffects in Experiment II (n = 12). Herefore, we used video-oculography during Free Visual Exploration, a sensitive and reliable tool to assess spatial attention over time. Listening to music with auditory spatialcueing - as compared to music without auditory spatialcueing - significantly improved neglect severity in terms of visual exploration behaviour for up to 3h. A voxel-based-lesion-symptom mapping analysis over all patients revealed that the response variability in listening to music with auditory spatial cueing is determined by the integrity of the right inferior parietal lobule, the second branch of the superior longitudinal fascicle, and parieto-parietal callosal fibres. Our study shows that listening to music with auditory spatial cueing significantly reduces neglect severity and has the potential to be used as an add-on in the neurorehabilitation of neglect.

Artificial Coherent States of Light by Multiphoton Interference in a Single-Photon Stream.

Coherent optical states consist of a quantum superposition of different photon number (Fock) states, but because they do not form an orthogonal basis, no photon number states can be obtained from it by linear optics. Here we demonstrate the reverse, by manipulating a random continuous single-photon stream using quantum interference in an optical Sagnac loop, we create engineered quantum states of light with tunable photon statistics, including approximate weak coherent states. We demonstrate this experimentally using a true single-photon stream produced by a semiconductor quantum dot in an optical microcavity, and show that we can obtain light with g^{(2)}(0)→1 in agreement with our theory, which can only be explained by quantum interference of at least 3 photons. The produced artificial light states are, however, much more complex than coherent states, containing quantum entanglement of photons, making them a resource for multiphoton entanglement.

First-line surgery in prolactinomas: lessons from a long-term follow-up study in a tertiary referral center.

CONTEXT: Although consensus guidelines recommend dopamine agonists (DAs) as the first-line approach in prolactinomas, some patients may opt instead for upfront surgery, with the goal of minimizing the need for continuation of DAs over the long term. While this approach can be recommended in selected patients with a microprolactinoma, the indication for upfront surgery in macroprolactinomas remains controversial, with limited long-term data in large cohorts. We aimed at elucidating whether first-line surgery is equally safe and effective for patients with micro- or macroprolactinomas not extending beyond the median carotid line (i.e., Knosp grade ≤ 1). METHODOLOGY: Retrospective study of patients with prolactinomas Knosp grade ≤ 1 treated with upfront surgery. The primary endpoint was patients' dependence on DAs at last follow-up. The secondary endpoint was postoperative complications. Independent risk factors for long-term dependence on DAs were analyzed. RESULTS: A microadenoma was noted in 45 patients (52%) and a macroadenoma in 41 (48%), with 17 (20%) harboring a Knosp grade 1 prolactinoma. Median follow-up was 80 months. First-line surgery resulted in long-term remission in 31 patients (72%) with a microprolactinoma and in 18 patients (45%) with a macroprolactinoma (p = 0.02). DA therapy was ultimately required in 11 patients (24%) with microadenomas vs. 20 (49%) with macroadenomas (p = 0.03). As for the latter, DA was required in 13 patients (76%) with Knosp grade 1 macroadenomas vs. 7 patients (29%) with Knosp grade 0 macroadenomas (p = 0.004). There was no mortality, and morbidity was minimal. Knosp grade 1 prolactinomas (OR 7.3, 95% CI 1.4-37.7, p = 0.02) but not adenoma size (i.e., macroprolactinomas) were an independent predictor of long-term dependence on DAs. CONCLUSIONS: First-line surgery in patients with microprolactinomas or macroprolactinomas Knosp grade 0 resulted in a good chance of non-dependency on DA therapy. However, in patients with prolactinomas Knosp grade 1, first-line surgery cannot be recommended, as adjuvant DA therapy after surgery is required in the majority of them over the long term.

Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells.

Hematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports proliferation and maintains HSC pluripotency would override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro, we optimized the HSC medium composition with a panel of cytokines and valproic acid and used an artificial 3D bone marrow-like scaffold made of polydimethylsiloxane (PDMS). This 3D scaffold offered a suitable platform to amplify human HSCs in vitro and, simultaneously, to support their viability, multipotency and ability for self-renewal. Silicon oxide-covering of PDMS structures further improved amplification of CD34+ cells, although the conservation of naïve HSCs was better on non-covered 3D PDMS. Finally, we found that HSC cultivated on non-covered 3D PDMS generated most pluripotent colonies within colony forming unit assays. In conclusion, by combining biological and biotechnological approaches, we optimized in vitro HSCs culture conditions, resulting in improved amplification, multipotency maintenance and vitality of HSCs.

Integration of expert knowledge in the definition of Swiss pear core collection.

Core collections (CCs) constitute a key tool for the characterization and management of genetic resources (GR). When the institutions involved in GR preservation decide to define a CC, they frequently prefer to select accessions based not only on strictly objective criteria, but also to add others following expert knowledge considerations (popularity, prestige, role in breeding history, or presence of phenotypic features of interest). The aim of this study was to evaluate the implications of approaches that combine formal analytical procedures and expert knowledge on the efficiency of CC definition through a case study to establish a pear CC from the Swiss National Pear Inventory. The CC had to represent a maximum of the genetic diversity, not to exceed 150 accessions, and required to include a priority set (SPPS) with 86 genotypes selected based on expert knowledge. In total, nine strategies were evaluated, resulting of combining compositions of the dataset sampled, sampling sizes and methods. The CCs sampled by mixed approaches provided similar scores, irrespective of the approach considered, and obtained similar efficiency in optimizing the genetic diversity retained. Therefore, mixed approaches can be an appropriate choice for applications involving genetic conservation in tree germplasm collections.

High risk of permanent stoma after anastomotic leakage in anterior resection for rectal cancer.

AIM: This study investigates how often bowel continuity was restored after anastomotic leakage in anterior resection for rectal cancer and assesses the clinical factors associated with permanent stoma. METHOD: The Swedish Colorectal Cancer Registry was used to identify cases of anastomotic leakage registered in southern Sweden between January 2001 and December 2011. Patient characteristics, surgical details and clinical information about the anastomotic leakages were retrieved from medical records. RESULTS: Of the 1442 patients operated on with anterior resection in 11 hospitals, 144 (10%) were diagnosed with anastomotic leakage after anterior resection for rectal cancer. After a median follow-up of 87 months (range 21-165), the overall rate of permanent stoma among patients with anastomotic leakage was 65%. Age ≥ 70 years (P = 0.02) and re-laparotomy (P < 0.001) were independently related to permanent stoma. Compared with nondefunctioned patients with anastomotic leakage, defunctioned patients with anastomotic leakage at the index procedure less often required re-laparotomy at some point during the entire clinical course (P < 0.001), but nondefunctioned and defunctioned patients with anastomotic leakage both had permanent stoma to the same extent (67% and 62%, respectively). CONCLUSION: Anastomotic leakage is highly associated with permanent stoma after anterior resection, especially in patients aged ≥ 70 years. In this cohort of patients with anastomotic leakage, 65% had permanent stoma at long-term follow-up. A defunctioning stoma ameliorates the clinical course but does not affect the end result of bowel continuity in established anastomotic leakage after anterior resection.

Observation of the Unconventional Photon Blockade.

We observe the unconventional photon blockade effect in quantum dot cavity QED, which, in contrast to the conventional photon blockade, operates in the weak coupling regime. A single quantum dot transition is simultaneously coupled to two orthogonally polarized optical cavity modes, and by careful tuning of the input and output state of polarization, the unconventional photon blockade effect is observed. We find a minimum second-order correlation g^{(2)}(0)≈0.37, which corresponds to g^{(2)}(0)≈0.005 when corrected for detector jitter, and observe the expected polarization dependency and photon bunching and antibunching; close by in parameter space, which indicates the abrupt change from phase to amplitude squeezing.

Electro-optic polarization tuning of microcavities with a single quantum dot.

We present an oxide aperture microcavity with embedded quantum dots which utilizes a three-contact design to independently tune the quantum dot wavelength and birefringence of the cavity modes. A polarization splitting tuning of ∼5 GHz is observed. For a typical microcavity polarization splitting, the method can be used to achieve perfect polarization degeneracy that is required for many polarization-based implementations of photonic quantum gates. The embedded quantum dot wavelength can be tuned into resonance with the cavity, independent of the polarization tuning.

Causes of mortality and morbidity in free-ranging mustelids in Switzerland: necropsy data from over 50 years of general health surveillance.

BACKGROUND: Although mustelids occur worldwide and include a wide range of species, little is known about the diseases affecting them. Mustelids have regularly been submitted for post mortem investigation in the framework of the program for general wildlife health surveillance in Switzerland, which has been in place for nearly 60 years. We performed a retrospective analysis of the necropsy reports on mustelids submitted to the diagnostic service of the University of Bern. The aims of this study were to present an overview of the causes of mortality and morbidity observed in these carnivores, to assess differences among species, to assess changes in disease detection over the study period, and to describe the pathology of selected diseases. RESULTS: Five hundred and sixty-six reports from 1958 to 2015 were analyzed. Most animals were stone martens (Martes foina, 46%) and badgers (Meles meles, 44%); the remaining species were polecats (Mustela putorius, 4.7%), pine martens (Martes martes, 2%), stoats (Mustela erminea, 1.4%), weasels (Mustela nivalis, 0.8%) and otters (Lutra lutra, 0.3%). Infectious diseases (n = 262) were frequent and were mostly bacterial or viral; non-infectious conditions (n = 169) were less common and were mostly traumatic or due to metabolic disorders. The most frequent diagnoses included distemper (75% were badgers), amyloidosis (96% were martens), bacterial respiratory infections (all mustelids), biting lice (badgers only) and pulmonary and gastro-intestinal helminths (all species). Less frequent diseases included histoplasmosis (badgers only), aspergillosis, toxoplasmosis, hepatozoonosis, and sarcoptic mange. Lesions due to infection with distemper virus were primarily appreciated in the respiratory tract and central nervous system; they presented species-specific characteristics such as necrosis in the ependyma in badgers and absence of syncytia in stone martens. Amyloidosis in martens was multisystemic in most cases and included both AA and AL amyloidosis; the main macroscopic change was severe splenomegaly. CONCLUSION: Infectious diseases were the most frequent causes of morbidity and mortality of mustelids, with marked species-specific differences. Lung and skin were the most commonly affected organs. Contagious diseases such as canine distemper, sarcoptic mange and rabies in mustelids showed a similar temporal pattern as in red foxes (Vulpes vulpes), suggesting pathogen spillovers from foxes to mustelids.

The spatial distribution of perseverations in neglect patients during a nonverbal fluency task depends on the integrity of the right putamen.

Deficient inhibitory control leading to perseverative behaviour is often observed in neglect patients. Previous studies investigating the relationship between response inhibition and visual attention have reported contradictory results: some studies found a linear relationship between neglect severity and perseverative behaviour whereas others could not replicate this result. The aim of the present study was to shed further light on the interplay between visual attention and response inhibition in neglect, and to investigate the neural underpinnings of this interplay. We propose the use of the Five-Point Test, a test commonly used to asses nonverbal fluency, as a novel approach in the context of neglect. In the Five-Point Test, participants are required to generate as many different designs as possible, by connecting dots within forty rectangles. We hypothesised that, because of its clear definition of perseverative errors, the Five-Point Test would accurately assess both visual attention as well as perseverative behaviour. We assessed 46 neglect patients with right-hemispheric stroke, and performed voxel-based lesion-symptom mapping (VLSM) to identify neural substrates of perseverative behaviour as well as the spatial distribution of perseverations. Our results showed that the Five-Point Test can reliably measure neglect and perseverative behaviour. We did not find any significant relationship between neglect severity and the frequency of perseverations. However, within the subgroup of neglect patients who displayed perseverative behaviour, the spatial distribution of perseverations significantly depended on the integrity of the right putamen. We discuss the putative role of the putamen as a potential subcortical hub to modulate the complex integration between visual attention and response inhibition processes.

In vivo selection of a multidrug-resistant Aeromonas salmonicida during medicinal leech therapy.

We report the selection in a 15-year-old boy of a multidrug-resistant, extended-spectrum ß-lactamase (ESBL)-producing Aeromonas salmonicida after medicinal leech therapy that required an antibiotic prophylaxis based on piperacillin/tazobactam and cotrimoxazole. Whole genome sequencing of the strain indeed revealed 13 antibiotic resistance genes, including the ESBL CTX-M-3 and the unusual ß-lactamase SCO-1.

Late leakage after anterior resection: a defunctioning stoma alters the clinical course of anastomotic leakage.

AIM: Anastomotic leakage (AL) is common after anterior resection (AR). Long term clinical outcomes of AL including late presenting leakage (LL) are not well studied. This study was undertaken to assess clinical features of LL with respect to incidence, association with predisposing factors and need for re-intervention. METHODS: The Swedish Colorectal Cancer Registry (SCRCR) was explored for AL cases after AR for rectal cancer in patients operated in the south of Sweden from 1 January 2001 to 31 December 2011. Demographic data, surgical technical details, number of postoperative days (POD) until diagnosis of AL, presenting symptoms, methods of diagnosis and treatment were retrieved from medical records. LL was defined according to different cut-offs as leakages occurring after hospital discharge (LLAHD), after 30 POD (LL ≥ POD 30) and after 90 POD (LL ≥ POD 90). RESULTS: In total, 1442 patients were operated on with AR of whom 144 cases of AL (10%) were identified. Median time from operation to follow-up was 87 months (range 21-162). LLAHD, LL ≥ POD 30 and LL ≥ POD 90 were present in 51%, 24% and 9% respectively. All categories of LL were associated with a defunctioning stoma. Relaparotomy was significantly less often employed in LLAHD, but not in other categories of LL. CONCLUSION: LL constitutes a substantial portion of all AL after AR for rectal cancer. The large proportion of LLAHD calls for awareness in the outpatient setting.

Aeromonas salmonicida type III secretion system-effectors-mediated immune suppression in rainbow trout (Oncorhynchus mykiss).

Aeromonas salmonicida subsp. salmonicida, the etiologic agent of furunculosis, is a major pathogen in aquaculture. Together with other pathogens, it is characterized by the presence of a type 3 secretion system (T3SS). The T3SS is the main virulence mechanism of A. salmonicida. It is used by the bacterium to secrete and translocate several toxins and effector proteins into the host cell. Some of these factors have a detrimental impact on the integrity of the cell cytoskeleton, likely contributing to impair phagocytosis. Furthermore, it has been suggested that effectors of the T3SS are able to modulate the host's immune response. Here we present the first partial characterization of the immune response in rainbow trout (Oncorhynchus mykiss) infected with distinct strains of A. salmonicida either carrying (i) a fully functional T3SS or (ii) a functionally impaired T3SS or (iii) devoid of T3SS ("cured" strain). Infection with an A. salmonicida strain either carrying a fully functional or a secretion-impaired T3SS was associated with a strong and persistent immune suppression. However, the infection appeared to be fatal only in the presence of a fully functional T3SS. In contrast, the absence of T3SS was neither associated with immune suppression nor fish death. These findings suggest that the T3SS and T3SS-delivered effector molecules and toxins of A. salmonicida do not only impair the host cells' cytoskeleton thus damaging cell physiology and phagocytosis, but also heavily affect the transcription of critical immune mediators including the shut-down of important warning signals to recognize infection and induce immune defense.

Nonlinear ptychographic coherent diffractive imaging.

Ptychographic Coherent diffractive imaging (PCDI) is a significant advance in imaging allowing the measurement of the full electric field at a sample without use of any imaging optics. So far it has been confined solely to imaging of linear optical responses. In this paper we show that because of the coherence-preserving nature of nonlinear optical interactions, PCDI can be generalised to nonlinear optical imaging. We demonstrate second harmonic generation PCDI, directly revealing phase information about the nonlinear coefficients, and showing the general applicability of PCDI to nonlinear interactions.

Purification of a single-photon nonlinearity.

Single photon nonlinearities based on a semiconductor quantum dot in an optical microcavity are a promising candidate for integrated optical quantum information processing nodes. In practice, however, the finite quantum dot lifetime and cavity-quantum dot coupling lead to reduced fidelity. Here we show that, with a nearly polarization degenerate microcavity in the weak coupling regime, polarization pre- and postselection can be used to restore high fidelity. The two orthogonally polarized transmission amplitudes interfere at the output polarizer; for special polarization angles, which depend only on the device cooperativity, this enables cancellation of light that did not interact with the quantum dot. With this, we can transform incident coherent light into a stream of strongly correlated photons with a second-order correlation value up to 40, larger than previous experimental results, even in the strong-coupling regime. This purification technique might also be useful to improve the fidelity of quantum dot based logic gates.

Ptychographic coherent diffractive imaging with orthogonal probe relaxation.

Ptychography is a scanning coherent diffractive imaging (CDI) technique that relies upon a high level of stability of the illumination during the course of an experiment. This is particularly an issue for coherent short wavelength sources, where the beam intensity is usually tightly focused on the sample in order to maximize the photon flux density on the illuminated region of the sample and thus a small change in the beam position results in a significant change in illumination of the sample. We present an improved ptychographic method that allows for limited stability of the illumination wavefront and thus significantly improve the reconstruction quality without additional prior knowledge. We have tested our reconstruction method in a proof of concept experiment, where the beam instability of a visible light source was emulated using a piezo driven mirror, and also in a short wavelength microscopy CDI setup using a high harmonic generation source in the extreme ultraviolet range. Our work shows a natural extension of the ptychography method that paves the way to use ptychographic imaging with any limited pointing stability coherent source such as free electron or soft X-ray lasers and improve reconstruction quality of long duration synchrotron experiments.

Occurrence of Brachyspira hyodysenteriae in multiplier pig herds in Switzerland.

OBJECTIVE: This research was aimed to determine the occurrence of Brachyspira (B.) hyodysenteriae in Swiss multiplier pig herds. MATERIALS AND METHODS: In a pilot study a direct real-time polymerase chain reaction (PCR) method for B. hyodysenteriae was compared to culture followed by PCR on 106 samples from three herds. Subsequently 40 multiplier herds were epidemiologically characterized and analysed for the presence of B. hyodysenteriae using direct PCR on 1412 rectal swabs. For external validation 20 swabs obtained from two positive conventional herds were analysed. RESULTS: The comparison of direct PCR with culture followed by PCR resulted in a moderate agreement (kappa index: 0.58). In the two conventional herds, 35% of the samples (7/20) tested positive. Samples from 39 multipliers tested negative. In one multiplier herd, 25% (9/36) of the samples tested PCR positive. Risk factors in the multiplier herd may have been rodents or birds, but not pig purchase. CONCLUSION AND CLINICAL RELEVANCE: B. hyodysenteriae have been detected in a Swiss multiplier herd, which underlines the threat of potential spread by replacement pigs. Consequently, a Brachyspira monitoring programme was established for Swiss multiplier herds.

Relation of intraoperative temperature to postoperative mortality in open colon surgery--an analysis of two randomized controlled trials.

INTRODUCTION: The open surgical wound is exposed to cold and dry ambient air resulting in heat loss mainly through radiation and convection. This cools the wound and promotes local vasoconstriction and hypoxia. Carbon dioxide (CO2) and water vapor are greenhouse gases with a warming effect. The aim was to evaluate if warm humidified CO2 insufflated in surgical wound can affect long-term overall mortality METHODS: This is a retrospective study of two clinical trials, where patients were randomized to warm humidified CO2 (n = 80) or not (n = 78). All patients underwent elective major open colon surgery. Patients in the treatment group received insufflation of warm humidified CO2 into the open wound cavity via a gas diffuser to create a local atmosphere of 100% CO2. Temperature in the wound cavity was measured with a heat-sensitive infrared camera. Core temperature was measured at the tympanic membrane. Median follow-up was 70.9 months. RESULTS: A multivariate analysis adjusted for age (p = 0.001) and cancer (p = 0.165) showed that the larger the temperature difference between final core temperature and wound edge temperature, the lower the overall survival rate (p = 0.050). Patients receiving insufflation of warm humidified CO2 had a tendency to a better overall survival compared with control patients (p = 0.508). End-of-operation wound edge temperature was negatively associated with mortality (OR = 0.80, 95% CI = 0.68-0.95, p = 0.011), whereas mortality was positively associated with age (10-year increase, OR = 1.78, 95% CI = 1.37-2.33, p < 0.001) and cancer (OR = 8.1, 95% CI = 1.95-33.7, p = 0.004). CONCLUSIONS: A small end-of-operation temperature difference between final core and wound edge temperature was positively associated with patient survival in open colon surgery.