Linear response theory of open systems with exceptional points.

Understanding the linear response of any system is the first step towards analyzing its linear and nonlinear dynamics, stability properties, as well as its behavior in the presence of noise. In non-Hermitian Hamiltonian systems, calculating the linear response is complicated due to the non-orthogonality of their eigenmodes, and the presence of exceptional points (EPs). Here, we derive a closed form series expansion of the resolvent associated with an arbitrary non-Hermitian system in terms of the ordinary and generalized eigenfunctions of the underlying Hamiltonian. This in turn reveals an interesting and previously overlooked feature of non-Hermitian systems, namely that their lineshape scaling is dictated by how the input (excitation) and output (collection) profiles are chosen. In particular, we demonstrate that a configuration with an EP of order M can exhibit a Lorentzian response or a super-Lorentzian response of order Ms with Ms = 2, 3, …, M, depending on the choice of input and output channels.

Quantum-inspired multicore optical fiber.

We introduce a new, to the best of our knowledge, type of multicore optical fiber having a quantum-inspired network topology and unique spectral features. Particularly, the connectivity between the cores is generated by unfolding a circular array of coupled quantum oscillators in Fock space. We show that in such a fiber geometry, the eigenvalues of the optical supermodes exhibit partial degeneracy and form a ladder. In turn, this leads to revival dynamics, allowing for a periodic re-imaging of the input intensity. As an example, we present a realistic design with six cores in silica glass platforms.

Giant sponge grounds of Central Arctic seamounts are associated with extinct seep life.

The Central Arctic Ocean is one of the most oligotrophic oceans on Earth because of its sea-ice cover and short productive season. Nonetheless, across the peaks of extinct volcanic seamounts of the Langseth Ridge (87°N, 61°E), we observe a surprisingly dense benthic biomass. Bacteriosponges are the most abundant fauna within this community, with a mass of 460 g C m-2 and an estimated carbon demand of around 110 g C m-2 yr-1, despite export fluxes from regional primary productivity only sufficient to provide <1% of this required carbon. Observed sponge distribution, bulk and compound-specific isotope data of fatty acids suggest that the sponge microbiome taps into refractory dissolved and particulate organic matter, including remnants of an extinct seep community. The metabolic profile of bacteriosponge fatty acids and expressed genes indicate that autotrophic symbionts contribute significantly to carbon assimilation. We suggest that this hotspot ecosystem is unique to the Central Arctic and associated with extinct seep biota, once fueled by degassing of the volcanic mounts.

Intergenerational learning: A recommendation for engaging youth to address marine debris challenges.

Youth can impact environmental attitudes and behaviors among adults. Indeed, research on intergenerational learning has demonstrated the influence of young people on adults in their lives for myriad environmental topics. Intergenerational learning (IGL) refers to the bidirectional transfer of knowledge, attitudes, or behaviors from children to their parents or other adults and vice versa. We suggest an educational framework wherein K-12 marine debris education designed to maximize IGL may be a strategy to accelerate interdisciplinary, community-level solutions to marine debris. Although technical strategies continue to be developed to address the marine debris crisis, even the most strictly technical of these benefit from social support. Here, we present 10 Best Practices grounded in educational, IGL, and youth civic engagement literature to promote marine debris solutions. We describe how integrating IGL and civic engagement into K-12-based marine debris curricula may start a virtuous circle benefiting teachers, students, families, communities, and the ocean.

Nonadditive Enhancement of Nonequilibrium Atom-Surface Interactions.

The motion-induced drag force acting on a particle moving parallel to an arrangement of N objects is analyzed. Particular focus is placed on the nonequilibrium statistics of the interaction and on the interplay between the system's geometry and the different dissipative processes occurring in realistic setups. We show that the drag force can exhibit a markedly nonadditive enhancement with respect to the corresponding additive approximation. The specific case of a planar cavity-a relevant configuration for many experiments-is calculated, showing an enhancement of about one order of magnitude. This and similar configurations are of significant potential interest for future measurements that aim to detect the drag force.

Quantum Rolling Friction.

An atom moving in a vacuum at constant velocity and parallel to a surface experiences a frictional force induced by the dissipative interaction with the quantum fluctuations of the electromagnetic field. We show that the combination of nonequilibrium dynamics, the anomalous Doppler effect, and spin-momentum locking of light mediates an intriguing interplay between the atom's translational and rotational motion. In turn, this deeply affects the drag force in a way that is reminiscent of classical rolling friction. Our fully non-Markovian and nonequilibrium description reveals counterintuitive features characterizing the atom's velocity-dependent rotational dynamics. These results prompt interesting directions for tuning the interaction and for investigating nonequilibrium dynamics as well as the properties of confined light.

Detection of Anomalous Cervical Internal Carotid Artery Branches by Colour Duplex Ultrasound.

OBJECTIVES: Conventional anatomical descriptions of the cervical internal carotid artery (ICA) report that no branches arise from this segment. However reports of ICA branches exist. The study aim was to determine the prevalence of anomalous branches of the ICA using colour duplex ultrasound (CDU). METHODS: Four hundred consecutive patients (800 carotid vessels) referred to a tertiary hospital vascular laboratory for investigation of carotid disease were included. A clear differentiation of a low resistive ICA and a high resistive external carotid artery (ECA) waveform was required. CDU was performed on a Philips IU22 ultrasound system with a 9-3 MHz linear array transducer employing a standard carotid imaging protocol. The origin of each ICA branch was identified using B-mode and CDU. Anatomical orientation of ICA branches and distance from bifurcation was recorded and spectral CDU analysis was performed. RESULTS: Twenty ICA branches, tracking cephaladly, were detected in 16 patients (4%), or 2.5% (20/800) vessels. The median age was 73 years; 50% were female and 50% male. All patients demonstrated a single branch [unilateral anomaly (n = 12 patients), bilateral anomaly (n = 4) patients]. Eighty-five percent arose from the posterior wall of the ICA. The median distance from ICA bifurcation was 4 mm (range 0-18 mm). ICA branch diameters ranged from 1.2 mm to 2.4 mm (median 1.4 mm, mean 1.6 mm). Eighty percent of ICA branches had less than 50% stenosis. Spectral analysis revealed high resistive waveforms in all branches. CONCLUSIONS: Branches from the ICA exist and can be characterised with CDU. Prevalence in a tertiary hospital referral cohort is 4%. Given their potential clinical implications, standard carotid imaging protocols should consider routine assessment and reporting of ICA branches.

Prevalence of paediatric inflammatory bowel disease in Sweden: a nationwide population-based register study.

BACKGROUND: We evaluated the impact of different case definition algorithms on the prevalence of paediatric inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) and to compare the occurrence of certain diseases compared to matched controls. METHODS: Paediatric patients (<18 years) were identified via ICD codes for UC and CD in Swedish registers between 1993 and 2010 (n = 1432). Prevalence was defined as ≥2 IBD-related visits. Prevalence of treated children in 2010 was defined as ≥2 IBD-related visits with one visit and ≥1 dispensed IBD-related drug prescription in 2010. To test the robustness of the estimates, prevalence was also calculated according to alternative case definitions. The presence of rheumatic, hepatobiliary, pancreatic, and dermatologic diseases were compared with age-/sex-/county-of-residence-matched general population controls. RESULTS: The IBD prevalence was 75/100,000 (CD: 29/100,000; UC: 30/100,000; patients with IBD-U: 16/100,000). Prevalence of treated disease in 2010 was 62/100,000 (CD: 23/100,000; UC: 25/100,000; patients with IBD-U: 13/100,000). When age restrictions were employed, the prevalence estimate decreased (<17y: 61/100,000, <16y: 49/100,000 and <15y: 38/100,000). Compared to general population controls (n = 8583), children with IBD had a higher prevalence of dermatologic (4.7% vs. 0.6%), hepatobiliary (including primary sclerosing cholangitis) (5.5% vs. 0.1%), pancreatic (1.7% vs. 0%) and rheumatic diseases (7.2% vs. 1.2%; all P < 0.01). CONCLUSIONS: The overall prevalence of paediatric IBD in Sweden was similar to that in earlier regional cohorts. IBD patients had a higher prevalence of comorbid conditions than matched general population controls.

[Autologous Skin Cell Transplantation and Medical Needling for Repigmentation of Depigmented Burn Scars on UV-protected and UV-exposed Skin]. / Autologe Hautzelltransplantation und Medical Needling zur Repigmentierung von depigmentierten Verbrennungsnarben an UV-exponierter und -geschützter Haut.

Background: Burn scars remain a serious physical and psychological problem for the affected people. Both clinical studies and basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient related to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling does not influence repigmentation of large hypopigmented scars. Objective: The goal is to evaluate whether both established methods - needling (improvement of scar quality) and non-cultured autologous skin cell suspension (NCASCS) "ReNovaCell" (repigmentation) - can be combined. So far, 20 patients with mean age of 33 years (6-60 years) with deep second and third degree burn scars have been treated. The average treated tissue surface was 94 cm² (15-250 cm²) and was focused on areas like face, neck, chest and arm. Methods: Medical needling is performed using a roller covered with 3 mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, NCASCS is applied, according to the known protocol. The patients have been followed up for 15 months postoperatively. The scars were subdivided into "UV-exposed" and "UV-protected" to discover whether the improved repigmentation is due to transfer of melanocytes or to reactivation of existing melanocytes after exposure to UV or the sun. Results: The objective measures show improved pigmentation in both UV-exposed and UV-protected groups. Melanin increases 1 year after NCASCS treatment in the UV-protected group are statistically significant. Conclusion: Medical needling in combination with NCASCS shows promise for repigmentation of burn scars, even in sun protected scars.

Failure of Local Thermal Equilibrium in Quantum Friction.

Recent progress in manipulating atomic and condensed matter systems has instigated a surge of interest in nonequilibrium physics, including many-body dynamics of trapped ultracold atoms and ions, near-field radiative heat transfer, and quantum friction. Under most circumstances the complexity of such nonequilibrium systems requires a number of approximations to make theoretical descriptions tractable. In particular, it is often assumed that spatially separated components of a system thermalize with their immediate surroundings, although the global state of the system is out of equilibrium. This powerful assumption reduces the complexity of nonequilibrium systems to the local application of well-founded equilibrium concepts. While this technique appears to be consistent for the description of some phenomena, we show that it fails for quantum friction by underestimating by approximately 80% the magnitude of the drag force. Our results show that the correlations among the components of driven, but steady-state, quantum systems invalidate the assumption of local thermal equilibrium, calling for a critical reexamination of this approach for describing the physics of nonequilibrium systems.

Combination of medical needling and non-cultured autologous skin cell transplantation (ReNovaCell) for repigmentation of hypopigmented burn scars.

Burn scars remain a serious physical and psychological problem for the affected people. Clinical studies as well as basic scientific research have shown that medical needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, medical needling has no influence on repigmentation of large hypopigmented scars. The goal of this study is to evaluate whether two established methods - needling (for improvement of scar quality) and non-cultured autologous skin cell suspension (for repigmentation) - can be successfully combined. Twenty subjects with mean age of 33 years (6-60 years) with scars from deep second and third degree burns have been treated. The average treated surface area was 94cm2 (15-250cm2) and was focused on prominent areas such as the face, neck, chest and arm. Percutaneous collagen induction or "medical needling" was performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (NCASCS) was produced and applied using the ReNovaCell Autologous Cell Harvesting Device (Avita Medical), according to the manufacturer's instructions. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, as well as with patient and observer ratings. Patient satisfaction/preference was also obtained. Taken together, the pigmentation ratings and objective measures indicate individual improvement in 17 of the study participants. The melanin increases seen 12 months after NCASCS treatment are statistically significant. Medical needling in combination with NCASCS shows promise for repigmentation of burn cars.

Combination of medical needling and non-cultured autologous skin cell transplantation (renovacell) for repigmentation of hypopigmented burn scars in children and young people.

Burn scars remain a serious physical and psychological problem for the affected. Clinical studies as well as basic scientific research have shown that Medical Needling can significantly increase the quality of burn scars with comparatively low risk and stress for the patient with regards to skin elasticity, moisture, erythema and transepidermal water loss. However, Medical Needling has no influence on repigmentation of large hypopigmented scars. The goal is to evaluate whether both established methods - Needling (improvement of scar quality) and ReNovaCell (repigmentation) - can be combined. So far, eight patients with mean age of 20 years (6-28 years) with deep second and third degree burn scars have been treated. The average treated tissue surface was 76cm² (15-250cm²) and was focused on areas like face, neck, chest and arm. Medical Needling is performed using a roller covered with 3mm long needles. The roller is vertically, horizontally and diagonally rolled over the scar, inducing microtrauma. Then, non-cultured autologous skin cell suspension (ReNovaCell) is applied, according to the known protocol. The patients were followed 12 months postoperatively. Pigmentation changes were measured objectively, and with patient and observer ratings. Patient satisfaction/preference was also obtained. We present the final study results. Taken together, pigmentation ratings and objective measures indicate improvement in six of the study participants. Melanin increase seen 12 months after ReNovaCell treatment in the study group as a whole is notable. Medical Needling in combination with ReNovaCell shows promise for repigmentation of burn scars.

Les séquelles de brûlures demeurent un problème physique et psychologique pour les victimes. Les études cliniques, ainsi que les recherches scientifiques ont montré que l'Aiguilletage médical peut améliorer de façon significative la qualité des cicatrices de brûlures avec un risque faible et un retentissement psychologique mineur chez les patients et ceci vis-à-vis de l'élasticité cutanée, l'hydratation, l'érythème et la déperdition hydrique trans épidermique. Cependant l'Aiguilletage médical n'a pas d'influence sur la repigmentation des vastes cicatrices hypo pigmentées. Le but est d'apprécier la possible association des deux méthodes: Aiguilletage (amélioration de la cicatrice) et ReNovaCell (re pigmentation). Ainsi 8 patients avec une moyenne d'age de 20 ans (6-28 ans) présentant des cicatrices de brûlures du 2e degré profond et 3e degré ont été traités. La moyenne de surface traitée était de 76cms carrés (15-20cms carrés) et les zones choisies furent la face, le cou, le thorax et les bras. L'Aiguilletage médical était réalisé avec un rouleau couvert d'aiguilles de 3mm de long. Le rouleau est manié verticalement, horizontalement et en diagonale sur la cicatrice provoquant un microtraumatisme. Puis, les cellules cutanées autologues non cultivées en suspension (ReNovaCell) sont appliquées suivant le protocole connu. Les patients furent suivis pendant 12 mois après le traitement. Les changements de pigmentation étaient mesurés de façon objective par le patient et évalués suivant une grille. La satisfaction du patient et son avis étaient alors notés. Nous présentons les résultats de la fin de notre étude. Prenant en compte les taux de repigmentation et les mesures objectives, l'amélioration fut constatée chez 6 de nos patients. L'augmentation de la mélanine fut observée 12 mois après le traitement par ReNovaCell dans l'ensemble du groupe de façon notable. L'association « Aiguilletage médical +ReNovaCell ¼ est riche de promesse pour la repigmentation des cicatrices de brûlures.

Clostridium perfringens enterotoxin and Clostridium difficile toxin A/B do not play a role in acute haemorrhagic diarrhoea syndrome in dogs.

Although an association between clostridial pathogens and canine idiopathic acute haemorrhagic diarrhoea syndrome (AHDS) has been described, the relevance of those bacteria and their toxins remains unclear. The aim of this study was to evaluate the association between severity of clinical signs and presence of Clostridium perfringens enterotoxin (CPE) and Clostridium difficile toxin A/B (CDT A/B) in faeces of dogs with AHDS. Faecal samples of 54 dogs with idiopathic AHDS were tested by qualitative CPE and CDT A/B ELISA, and PCR was performed to detect enterotoxin genes of C. perfringens (cpe) and toxin B genes of C. difficile (cdt b). Prevalence of cdt b and CDT A/B in dogs with AHDS was 10/54 and 2/54 versus 3/23 and 0/23 in control dogs. Prevalence of cpe was 35/54 in affected versus 9/23 in control dogs. Prevalence of CPE in dogs with AHDS (13/54) was higher compared with control dogs (0/23). No significant difference was detected between CPE-positive and -negative and between cpe-positive and -negative dogs in severity of clinical signs, duration of hospitalisation, mortality rate and selected laboratory parameters. This study suggests that CPE and CDT A/B do not play a role in idiopathic AHDS, are not associated with clinical parameters in affected dogs and cannot be used to predict disease outcome.

[Acute haemorrhagic diarrhoea as a presenting sign in a dog with primary hypoadrenocorticism]. / Akuter blutiger Durchfall als Vorstellungsgrund bei einem Hund mit primärem Hypoadrenokortizismus.

A 7-year-old male castrated mixed breed dog was presented because of acute haemorrhagic vomiting and watery haemorrhagic diarrhoea. According to clinical signs, nonspecific clinicopathological abnormalities, normal electrolytes and a rapid improvement with fluid therapy, haemorrhagic gastroenteritis (HGE) was suspected. One month later the dog was represented with weakness and electrolyte changes characteristic for typical hypoadrenocorticism (hyperkalaemia and hyponatraemia) were found. The tentative diagnosis was confirmed using an ACTH stimulation test. This case report highlights that dogs with hypoadrenocorticism may be presented with acute haemorrhagic diarrhoea. Electrolyte changes characteristic for hypoadrenocorticism may not be present in case of gastrointestinal potassium loss because of vomiting and diarrhoea. To rule out hypoadrenocorticism, a basal cortisol measurement should be performed in every dog with acute haemorrhagic diarrhoea of unknown cause.

Endoscopically visualized lesions, histologic findings, and bacterial invasion in the gastrointestinal mucosa of dogs with acute hemorrhagic diarrhea syndrome.

BACKGROUND: Etiology of hemorrhagic gastroenteritis (HGE) syndrome in dogs is unknown and histopathologic and microbial investigations have only been performed post mortem. OBJECTIVE: To identify characteristic intra vitam endoscopic and histologic mucosal lesions, as well as bacterial species, within the mucosa of dogs with HGE. ANIMALS: Ten dogs diagnosed with HGE were included. Eleven dogs with gastroduodenoscopy and different intestinal diseases were used as controls for microbial changes. Dogs pretreated with antibiotics or diagnosed with any disease known to cause bloody diarrhea were excluded from the study. METHODS: In this prospective study, gastrointestinal biopsies were collected from 10 dogs with HGE. Endoscopic and histologic changes were assessed according to WSAVA guidelines. Biopsies from the stomach, duodenum, ileum, and colon were investigated by histology and by immunohistochemistry for the presence of Clostridium spp. and parvovirus. The first duodenal biopsy taken with a sterile forceps was submitted for bacterial culture. RESULTS: Acute mucosal lesions were only found in the intestines, not in the stomach. Clostridium spp., identified as Clostridium perfringens in 6/9 cases, were detected on the small intestinal mucosa in all dogs with HGE, either by culture or immunohistopathology. In the control group, C. perfringens could only be cultured in one of 11 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study demonstrate an apparent association between C. perfringens and the occurrence of acute hemorrhagic diarrhea. The term "HGE," which implies the involvement of the stomach, should be renamed as "acute hemorrhagic diarrhea syndrome."

Nationwide prevalence of inflammatory bowel disease in Sweden: a population-based register study.

BACKGROUND: Regional studies on inflammatory bowel disease (IBD) suggest an increasing prevalence over time, but no nationwide estimate has been published so far. AIM: To estimate the IBD prevalence in 2010 in Sweden overall, by disease, and in specific patient segments. METHODS: Patients were identified according to international classification codes for ulcerative colitis and Crohn's disease in in-patient care (1987-2010), day surgery and nonprimary out-patient care (1997-2010) in the nationwide Swedish Patient Register. RESULTS: Requiring two or more diagnoses of IBD in nonprimary care, a total of 61 344 individuals with physician-diagnosed IBD were alive in Sweden in 2010 (mean age 50 years; 51% men), corresponding to a prevalence of 0.65% (95% CI, 0.65-0.66). The prevalence increased with age, and peaked in women at ages 50-59 years and in men at ages 60-69 years. Adding the requirement of IBD as main (vs. main or contributory) diagnosis code, or diagnosis from an internal medicine/gastroenterology/surgery department did not change the prevalence estimate. Prevalence of actively treated disease (defined as two or more IBD-related visits, of which one occurred in 2010, plus at least one dispensed prescription of IBD-related drugs in 2010) was 0.27% (95% CI, 0.27-0.28). CONCLUSIONS: The Swedish nationwide register-based IBD prevalence was higher compared with previous Swedish and international estimates. While prevalence estimates were robust across different case definitions, once two or more visits were required, only about one-third of prevalent patients were drawing resources from specialised care in 2010.

Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans.

Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O2 and CO2. CO2 is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO2 changes. CO2 evokes distinct AFD Ca²âº responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO2 responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO2. Surprisingly, gradients of 0.01% CO2/second evoke very different Ca²âº responses from gradients of 0.04% CO2/second. Ambient O2 provides further contextual modulation of CO2 avoidance. At 21% O2 tonic signalling from the O2-sensing neuron URX inhibits CO2 avoidance. This inhibition can be graded according to O2 levels. In a natural wild isolate, a switch from 21% to 19% O2 is sufficient to convert CO2 from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O2 on CO2 avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO2-evoked Ca²âº responses. Ambient O2 and acclimation temperature act combinatorially to modulate CO2 responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans.

The oncolytic adenovirus AdΔΔ enhances selective cancer cell killing in combination with DNA-damaging drugs in pancreatic cancer models.

Pancreatic adenocarcinomas are aggressive and frequently develop resistance to all current therapies. Replication-selective adenoviruses can overcome resistance to chemotherapeutics through their sensitizing effects on drug-induced cell killing. We previously found that adenovirus deleted in the anti-apoptotic E1B19K gene enhanced gemcitabine-induced apoptotis. Here we demonstrate that our engineered double-deleted AdΔΔ mutant (deleted in the pRb-binding E1ACR2 region and E1B19K) selectively replicates and enhances cell killing in combination with DNA-damaging cytotoxic drugs in pancreatic cancer cells. Combinations of AdΔΔ with gemcitabine, irinotecan or cisplatin resulted in two- to fourfold decreases in EC(50) (half maximal effective concentration) values and was more efficent than similar combinations with wild-type virus, the dl1520 (ONYX-015) and dl922-947 mutants. AdΔΔ replication was impaired in normal bronchial human epithelial cells and did not sensitize the cells to drugs. Gemcitabine-insensitive AsPC-1, BxPC-3 and PANC-1 cells were efficiently killed by irinotecan in combination with AdΔΔ. Suboptimal doses of AdΔΔ and gemcitabine significantly prolonged time to tumor progression in two human pancreatic tumor xenograft in vivo models, PT45 and SUIT-2. We conclude that AdΔΔ has low toxicity to normal cells while potently sensitizing pancreatic cancer cells to DNA-damaging drugs, and holds promise as an improved therapeutic strategy for pancreatic cancer.