Persistent Self-Induced Larmor Precession Evidenced through Periodic Revivals of Coherence.

Interferometric measurements of an optically trapped exciton-polariton condensate reveal a regime where the condensate pseudo-spin precesses persistently within the driving optical pulse. For a single 20 µs optical pulse, the condensate pseudo-spin undergoes over 10^{5} full precessions with striking frequency stability. The emergence of the precession is traced to polariton nonlinear interactions that give rise to a self-induced out-of-plane magnetic field, which in turn drives the system spin dynamics. The Larmor precession frequency and trajectory are directly influenced by the condensate density, enabling the control of this effect with optical means. Our results accentuate the system's potential for the realization of magnetometry devices and can lead to the emergence of spin-squeezed polariton condensates.

Engineering Photon Statistics in a Spinor Polariton Condensate.

We implement full polarization tomography on photon correlations in a spinor exciton-polariton condensate. Our measurements reveal condensate pseudospin mean-field dynamics spanning from stochastic switching between linear polarization components, limit cycles, and stable fixed points, and their intrinsic relation to the condensate photon statistics. We optically harness the cavity birefringence, polariton interactions, and the optical orientation of an incoherent exciton reservoir to engineer photon statistics with precise control. Our results demonstrate a smooth transition from a highly coherent to a super-thermal state of the condensate polarization components.

Quantum fluids of light in all-optical scatterer lattices.

One of the recently established paradigms in condensed matter physics is examining a system's behaviour in artificial potentials, giving insight into phenomena of quantum fluids in hard-to-reach settings. A prominent example is the matter-wave scatterer lattice, where high energy matter waves undergo transmission and reflection through narrow width barriers leading to stringent phase matching conditions with lattice band formation. In contrast to evanescently coupled lattice sites, the realisation of a scatterer lattice for macroscopic matter-wave fluids has remained elusive. Here, we implement a system of exciton-polariton condensates in a non-Hermitian Lieb lattice of scatterer potentials. By fine tuning the lattice parameters, we reveal a nonequilibrium phase transition between distinct regimes of polariton condensation: a scatterer lattice of gain guided polaritons condensing on the lattice potential maxima, and trapped polaritons condensing in the potential minima. Our results pave the way towards unexplored physics of non-Hermitian fluids in non-stationary mixtures of confined and freely expanding waves.

Synthetic band-structure engineering in polariton crystals with non-Hermitian topological phases.

Synthetic crystal lattices provide ideal environments for simulating and exploring the band structure of solid-state materials in clean and controlled experimental settings. Physical realisations have, so far, dominantly focused on implementing irreversible patterning of the system, or interference techniques such as optical lattices of cold atoms. Here, we realise reprogrammable synthetic band-structure engineering in an all optical exciton-polariton lattice. We demonstrate polariton condensation into excited states of linear one-dimensional lattices, periodic rings, dimerised non-trivial topological phases, and defect modes utilising malleable optically imprinted non-Hermitian potential landscapes. The stable excited nature of the condensate lattice with strong interactions between sites results in an actively tuneable non-Hermitian analogue of the Su-Schrieffer-Heeger system.

Optical Control of Couplings in Polariton Condensate Lattices.

We demonstrate deterministic control of the nearest and next-nearest neighbor coupling in the unit cell of a square lattice of microcavity exciton-polariton condensates. We tune the coupling in a continuous and reversible manner by optically imprinting potential barriers of variable height, in the form of spatially localized incoherent exciton reservoirs that modify the particle flow between condensates. By controlling the couplings in a 2×2 polariton cluster, we realize ferromagnetic, antiferromagnetic, and paired ferromagnetic phases and demonstrate the potential scalability of the system.

Transition from Propagating Polariton Solitons to a Standing Wave Condensate Induced by Interactions.

We explore phase transitions of polariton wave packets, first, to a soliton and then to a standing wave polariton condensate in a multimode microwire system, mediated by nonlinear polariton interactions. At low excitation density, we observe ballistic propagation of the multimode polariton wave packets arising from the interference between different transverse modes. With increasing excitation density, the wave packets transform into single-mode bright solitons due to effects of both intermodal and intramodal polariton-polariton scattering. Further increase of the excitation density increases thermalization speed, leading to relaxation of the polariton density from a solitonic spectrum distribution in momentum space down to low momenta, with the resultant formation of a nonequilibrium condensate manifested by a standing wave pattern across the whole sample.

Spin Order and Phase Transitions in Chains of Polariton Condensates.

We demonstrate that multiply coupled spinor polariton condensates can be optically tuned through a sequence of spin-ordered phases by changing the coupling strength between nearest neighbors. For closed four-condensate chains these phases span from ferromagnetic (FM) to antiferromagnetic (AFM), separated by an unexpected crossover phase. This crossover phase is composed of alternating FM-AFM bonds. For larger eight-condensate chains, we show the critical role of spatial inhomogeneities and demonstrate a scheme to overcome them and prepare any desired spin state. Our observations thus demonstrate a fully controllable nonequilibrium spin lattice.

Steady-state serum concentrations of venlafaxine in patients with late-life depression. Impact of age, sex and BMI.

Diagnosis of late-life depression is given when depressive symptoms emerge in persons older than 65 years. Great care is needed when elderly patients receive psychopharmacotherapy due to altered pharmacokinetic status. As a consequence, age is considered to have a significant effect on serum concentrations of antidepressant drugs. The magnitudes of age-dependent changes, however, are uncertain. By utilizing a large therapeutic drug monitoring (TDM) database, this cross-sectional study aimed to retrospectively assess pharmacotherapy in elderly patients in comparison with their younger counterparts, when treated with venlafaxine, which is widely used to treat late-life depression. In addition, the influence of sex and body mass index (BMI) was evaluated. Serum concentrations of venlafaxine and its active metabolite O-desmethylvenlafaxine requested during routine TDM in two University Medical Centers in Germany were analyzed. Patients with concomitant CYP2D6 inhibiting drugs as co-medication were excluded. In total, 1,417 samples were available for the analysis. Elderly patients had by average 42% higher dose-adjusted serum concentrations (ng/mL/mg) of the active moiety (venlafaxine plus O-desmethylvenlafaxine) than younger patients. In addition, our study demonstrated that the difference between age groups is independent of sex and BMI. However, age groups only explain 4.5% of the total dose-adjusted serum concentration variation of the venlafaxine active moiety. Dose adjustments for venlafaxine are recommended in patients aged 65 years or older, particularly in elderly female patients who are exceptionally vulnerable to high serum concentrations of venlafaxine. TDM is recommended during venlafaxine pharmacotherapy.

Outcome predictors in acute surgical admissions for lower gastrointestinal bleeding.

AIM: The BLEED criterion is a triaging model for lower gastrointestinal bleeding (LGIB), which was developed and validated in the USA. We assessed the BLEED criteria in a UK population and aimed to elucidate factors that can be implemented for early risk stratification. METHOD: Patients were identified from a prospectively maintained surgical admission database at a central London teaching hospital. Data were collected on 26 clinical factors available on initial presentation. The primary-outcome end-points included severe bleeding (persistent bleeding within the first 24 h, blood transfusion, a decrease in haematocrit of ≥ 20% or recurrent bleeding after ≥ 24 hours of stability) and adverse outcome (emergency surgery to control bleeding, intensive care unit [ITU] admission or death). RESULTS: One hundred and eighty-four clinical episodes were identified, representing 3% of all surgical referrals. Twelve patients with upper gastrointestinal bleeding were excluded. Severe bleeding occurred in 110 (64%) patients. An adverse outcome was recorded in 20 (11.6%) patients, and 10 (5.4%) patients died during admission. The commonest aetiologies were diverticular disease, haemorrhoids and malignancy. Four prognosticators of adverse outcome were identified, these being: creatinine > 150 µm (P = 0.002); age > 60 years (P = 0.001); abnormal haemodynamic parameters on presentation (P = 0.05); persistent bleeding within the first 24 h (P = 0.05); and area under the receiver-operating characteristics curve (AUC) = 0.79. The BLEED criteria were shown to be nonpredictive (AUC = 0.60). CONCLUSION: The BLEED criterion was not shown to have any predictive value in this patient cohort. Our study has determined an independent set of prognostic factors that could be incorporated into initial triaging of patients presenting with LGIB. This may facilitate the early identification of patients requiring more aggressive resuscitation, admission to a monitored bed and consideration for early radiological or surgical intervention.

Rectal cancer with macroscopic peritoneal involvement--clinical challenges and consequences.

OBJECTIVE: In gastrointestinal cancer, serosal involvement indicates advanced disease. We looked at the possible role of clinical peritoneal involvement (CPI) in local recurrences (LRs) and the overall survival of patients with rectal cancer (RC). METHOD: Between 1993 and 2002, 6404 patients were diagnosed with RC. Based on macroscopic findings at surgery and corresponding histological findings, 166 patients (3%) had CPI. Surgery was stratified according to type and extent of operation: as resective or nonresective surgery and as curative (R0) or noncurative (R1 or R2) resection. RESULTS: The presence of CPI was a negative factor for survival with a median of 15 months (95% CI, 12-19) in the presence of CPI compared with 65 months (95% CI, 61-70) without it (P < 0.001). In R0 resections, the median survival was 97 months (95% CI, 90-102) in patients without CPI compared with 48 months (95% CI, 22-74) in patients with CPI (P < 0.001). In R1 or R2 resections, the median survival was 16 months (95% CI, 15-17) in the absence of CPI and 9 months (95% CI, 8-10) in the presence of CPI. The LR rate in patients without CPI was 10.2% compared with 15.7% in patients with CPI (P = 0.022). CONCLUSIONS: Clinical peritoneal involvement is a significant detrimental prognostic factor for the LR of RC and survival in the absence of metastases. Observations from this large national cohort add to what is known about peritoneal involvement. Diagnosed CPI should be taken into consideration when adjuvant treatment strategies are addressed.

Topical drug delivery to the posterior segment of the eye: anatomical and physiological considerations.

Drug delivery to the posterior segment of the eye is important for potentially treating various disorders in retina, choroid, vitreous humor and optic nerve. Due to anatomic membrane barriers and the lacrimal drainage it can be quite challenging to obtain therapeutic drug concentrations in the posterior parts of the eye after topical drug administration. Since the membrane barriers cannot be altered with non-invasive methods invasive methods such as direct drug injection into the vitreous humor and subconjunctival, subtenons capsule or suprascleral injections are gaining popularity. However, invasive methods can cause discomfort for the patient and can also lead to complications that are even more serious than the disease being treated. Alternatively, novel ophthalmic formulations can be developed that specifically target topical drug delivery to the posterior segment of the eye. Anatomical and physiological barriers in the eye are reviewed as well as the theoretical model of passive drug diffusion from the eye surface into the eye. It is shown that enhanced drug delivery through conjunctiva/sclera to retina can be obtained by formulating lipophilic drugs as hydrophilic drug/cyclodextrin complex solutions. Optimization of the delivery system by formulating the drug as a low-viscosity aqueous drug/cyclodextrin complex suspension results in sustained high concentrations of dissolved drug in the tear fluid which further increases the targeted drug delivery to the posterior segment.

Palliative surgery for rectal cancer in a national cohort.

OBJECTIVE: Whether resection of the primary tumour is of benefit to patients with incurable rectal cancer (RC) remains a matter of debate. In this study we analyse prospectively recorded data from a national cohort. METHOD: Among 4831 patients diagnosed with RC between 1997 and 2001, 838 (17%) patients were treated with palliative surgery. Patients were stratified according to disease stage, age and type of surgery. RESULTS: A significantly longer median survival, 12 (range 10-13) months, was observed in patients treated with resection of the primary tumour compared with 5 (range 4-6) months in patients treated with nonresective procedures (P < 0.001). Median survival in months was significantly (P < 0.001) related to age (13; < 60 years of age, 10; 60 to 69 years, 7; 70 to 79 years, 6; >/= 80 years of age). In patients over 80 years, survival was similar regardless of the treatment. Thirty-day mortality varied from 2.5% to 20%, according to age groups. CONCLUSION: The longer survival observed in patients with resection of the primary tumour may partly be explained by patient selection. Elderly patients (>/= 80 years) had a similar survival, irrespective of resection of the primary tumour or not. Careful consideration of the individual patient, extent of disease and treatment-related factors are important in decision-taking for palliative treatment for patients with advanced RC.

Quality of life and functional outcome following anterior or abdominoperineal resection for rectal cancer.

AIMS: The aims of the study were (1) to evaluate quality of life (QoL) and functional outcome in patients following anterior resection (AR) or abdominoperineal resection (APR) for rectal cancer, and (2) whether these outcomes were dependent on the level of anastomosis. METHODS: Patients who were without recurrent or metastatic disease were identified from the Norwegian Rectal Cancer Registry. QoL was assessed by the EORTC questionnaires QLQ-C30 and QLQ-CR38, and rectal function by a short questionnaire. Of 319 patients studied, 229 had undergone AR and 90 APR. The median age was 73 years, and the median time since surgery was 64 months. RESULTS: Mean QoL scores for body image and male sexual problems were better following AR than APR (P<0.01), also in patients with a low (< or = 3 cm) anastomosis. Patients who had undergone AR had higher mean scores for constipation (P<0.001) and more often used anti-diarrhoeal medication (P=0.005), than patients who had undergone APR. Patients with a low anastomosis (< or = 3 cm) had more incontinence for gas and solid stools (P<0.05), and had more incontinence (P=0.006) compared with patients with higher anastomosis, but there was no difference in QoL. Subgroup analysis showed that irradiated patients (n=34) had worse rectal function in terms of frequency, urgency, and incontinence (P<0.01). CONCLUSIONS: Although rectal function was impaired in patients with low anastomosis, patients who had undergone AR had better QoL than patients who had undergone APR.

Infestation of Werneckiella equi on Icelandic horses, characteristics of predilection sites and lice dermatitis.

Lice infestations on horses caused by the lice Werneckiella (Damalinia) equi and Haematopinus equi are observed worldwide. In this study, the distribution and clinical manifestations of lice on Icelandic horses were examined. Thirty-eight out of 93 animals (40.86%) were identified as infested with W. equi. Sixty-eight animals (73.12%) presented dermatological lesions associated with lice infestation, while only 32 of these animals presented lice. Six animals had no clinical signs although of being lice-positive, and 19 animals (20.43%) showed neither lice nor clinical manifestations. Lice burdens varied from animal to animal, and clinical manifestations occurred at all levels of infestation. Focal alopecia was the main clinical sign (83.78%) on lice-positive horses, while scaling and crusts occurred in 10.81% and 9.68% of the cases, respectively. Clinical signs present in the head and the neck/mane area were found to be an indication of lice infestation in horses.

The time pattern of bilateral exudative age-related macular degeneration.

PURPOSE: To study time patterns in bilateral exudative age-related macular degeneration (AMD) and the pattern of drusen before and after the onset of exudative AMD. MATERIAL AND METHODS: Out of 2220 individuals in the Icelandic genetic study of AMD, 151 had bilateral exudative AMD. We searched for previous records in the Icelandic University Retina Unit. For the 65 patients with a fluorescein angiography record of both eyes, we established the time between the onset of disease in each eye. For the 53 patients with colour fundus photographs of the latter eye taken prior to the occurrence of exudative disease, we graded the drusen before and after the onset of exudative AMD in the second eye. RESULTS: The time interval between the onset of exudative AMD in the first and second eyes was 2.5 years (95% CI: 1.8-3.2; n = 65) and the median was 1.8 years. In 82% of cases the second eye was affected within 4 years. Soft drusen in the macula were found in 95% of eyes that later developed exudative disease (n = 53). Soft and hard drusen decreased in number in the central macula following the development of exudative disease. CONCLUSIONS: Bilateral exudative AMD develops within a few years in both eyes. Drusen are less visible following the onset of exudative AMD in the second eye.

Natural infestation of the chewing lice (Werneckiella equi) on horses and treatment with imidacloprid and phoxim.

Infestation with the chewing louse (Werneckiella (Damalinia) equi) can be found on horses world-wide. Louse infestations, including clinical signs of louse-derived dermatitis, are known from Icelandic horses. A clinical field investigation was conducted in Iceland using horses with natural louse infestations to evaluate the efficacy of imidacloprid in a 10% solution in comparison with phoxim in a 0.05% solution. A total of 27 horses received a single imidacloprid treatment using 16 ml of the 10% solution along the mane and on the dorso-lateral trunk. A further 43 horses were treated twice, 14 days apart, with phoxim, using 2 x 50 ml solution applied along the mane and the dorso-lateral trunk. At the final evaluation on day 28, complete control of the lice was obtained for the imidacloprid treated horses and only a single moribund louse was found on two horses treated with phoxim.

Preparation of solid drug/cyclodextrin complexes of acidic and basic drugs.

One of the main obstacles in pharmaceutical applications of cyclodextrins is their increase of the formulation bulk. Even at maximum incorporation 500 mg of a solid drug/cyclodextrin complex will only contain between 50 and 125 mg of the drug, assuming a low molecular weight drug (MW 200 to 400 Dalton) and an average molecular weight cyclodextrin (MW about 1500 Dalton). In general, the complexation efficiency is low and consequently the complex powder contains a significant amount of empty cyclodextrin molecules. In the present study the complexation efficiency is increased by ionization of the drug molecule through addition of volatile acid (i.e. acetic acid) or base (i.e. ammonia) to the aqueous complexation media of basic or acidic drugs, respectively. The volatile acid or base was then removed during lyophilization and heating in a vacuum oven resulting in formation of solid cyclodextrin complexes of the unionized drug. Thus, the complexation efficiency was temporary increased by the ionization but then again decreased leading to formation of the thermodynamically unstable solid drug/cyclodextrin complexes. When dissolved the energy of the system was lowered by expelling the drug molecules from the cyclodextrin cavities resulting in formation of supersaturated drug solutions and ultimately precipitation of the drug.

Risk factors associated with hindlimb lameness and degenerative joint disease in the distal tarsus of Icelandic horses.

The aim of this study was to evaluate potential risk factors associated with hindlimb lameness and radiographic signs of degenerative joint disease (DJD) in the distal tarsus in Icelandic horses. The material consisted of riding horses (n = 420) age 6-12 years sired by 17 selected sires representing all major breeding lines, and of riding horses (n = 194) in the same age range sired by other sires. The examination protocol included the following: interview with owners/trainers, assessment of conformation, motion evaluation and radiographic examination. At the interview, data related to factors outside the horse (environmental variables) and data associated directly with the horse (intrinsic variables) were obtained. Data analysis was performed in 2 steps: screening using bivariate analysis, followed by testing with a multivariate logistic regression model. In the multivariate analysis, the factors of sire, age when broken to saddle and stud show participation were strongly associated with the prevalence of lameness. Height at the croup and ability to perform different gaits were also associated with the prevalence of lameness, but to a lesser degree. The risk factors of age, tarsal angle and birthplace were significantly associated with radiographic signs of DJD in the distal tarsus. Neither the variation in applied training intensity, the use of a professional or amateur trainer nor the temperament or front limb action of the individual horse was significantly associated with the prevalence of hindlimb lameness and/or radiographic signs of DJD in the distal tarsus in the Icelandic horse.

Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray.

The cyclodextrin solubilization of three benzodiazepines, i.e. alprazolam, midazolam and triazolam, was investigated. The cyclodextrin solubilization was enhanced through ring-opening of the benzodiazepine rings and ionization of the ring-open forms. Additional enhancement was obtained through interaction of a water-soluble polymer with the cyclodextrin complexes. The ring-opening was pH-dependent and completely reversible, the ring-open forms dominating at low pH but the ring-closed forms at physiologic pH. The ring-closed forms were rapidly regenerated upon elevation of pH. In freshly collected human serum in vitro at 37 degrees C, the half-life for the first-order rate constant for the ring-closing reaction was estimated to be less than 2 min for both alprazolam and midazolam. Midazolam (17 mg/ml) was solubilized in aqueous pH 4.3 nasal formulation containing 14% (w/v) sulfobutylether beta-cyclodextrin, 0.1% (w/v) hydroxypropyl methylcellulose, preservatives and buffer salts. Six healthy volunteers received 0.06 mg/kg midazolam intranasally and 2 mg intravenously, and blood samples were collected up to 360 min after the administration. Midazolam was absorbed rapidly reaching maximum serum concentrations of 54.3+/-5.0 ng/ml at 15+/-2 min. The elimination half-life of midazolam was 2.2+/-0.3 h and the absolute availability was 73+/-7%. All mean values+/-SEM.