Learning Generative Models Using Denoising Density Estimators.

Learning probabilistic models that can estimate the density of a given set of samples, and generate samples from that density, is one of the fundamental challenges in unsupervised machine learning. We introduce a new generative model based on denoising density estimators (DDEs), which are scalar functions parametrized by neural networks, that are efficiently trained to represent kernel density estimators of the data. Leveraging DDEs, our main contribution is a novel technique to obtain generative models by minimizing the Kullback-Leibler (KL)-divergence directly. We prove that our algorithm for obtaining generative models is guaranteed to converge consistently to the correct solution. Our approach does not require specific network architecture as in normalizing flows (NFs), nor use ordinary differential equation (ODE) solvers as in continuous NFs. Experimental results demonstrate substantial improvement in density estimation and competitive performance in generative model training.

COVID-19: Seroprevalence and Vaccine Responses in UK Dental Care Professionals.

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.

Anterior cervical spine blood supply: a cadaveric study.

PURPOSE: To describe the origin of the vessels supplying the anterior sub-axial cervical vertebrae (C3-C7) to further understand their potential influence on anterior bone loss after anterior cervical spinal surgery. METHOD: Cadaveric dissection was performed on ten adult human necks after latex perfusion of their subclavian, common carotid and vertebral arteries. The nutrient vessels of the sub-axial cervical spine were identified and traced to their origin. The course and distribution of these vessels and their nutrient foraminae are described. RESULTS: In all cases the anterior nutrient vessels were derived from the thyro-cervical trunk with branches that passed over the longus coli muscles forming a leash of vessels in the pre-vertebral fascia which subsequently extended in a frond-like pattern to pass onto the anterior aspect of vertebrae. The more cranial the cervical level the fewer the number of nutrient vessels and foraminae. The distribution of the foraminae on the anterior vertebral body followed the oblique supero-medial course of the nutrient vessels. CONCLUSION: Nutrient vessels perforate the cervical vertebrae on their anterior surface. These are derived from a leash of vessels that lie within the pre-vertebral fascia overlying the longus coli muscles. The origin of these vessels is the ascending cervical artery with a variable contribution from the transverse cervical artery.

Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables.

BACKGROUND: Cobalt chloride (CoCl2 ) is administered to racehorses to enhance performance. The purpose of this study was to evaluate the clinical, cardiovascular, and endocrine effects of parenterally administered CoCl2 . OBJECTIVES: To describe the effects of weekly intravenous doses of CoCl2 on Standardbred horses. ANIMALS: Five, healthy Standardbred mares. METHODS: Prospective, randomized, experimental dose-escalation pilot. Five Standardbred mares were assigned to receive 1 of 5 doses of CoCl2 (4, 2, 1, 0.5, or 0.25 mg/kg) weekly IV for 5 weeks. Physical examination, blood pressure, cardiac output, and electrocardiography (ECG) were evaluated for 4 hours after administration of the first and fifth doses. Blood and urine samples were collected for evaluation of cobalt concentration, CBC and clinical chemistry, and hormone concentrations. RESULTS: All mares displayed pawing, nostril flaring, muscle tremors, and straining after CoCl2 infusion. Mares receiving 4, 2, or 1 mg/kg doses developed tachycardia after dosing (HR 60-126 bpm). Ventricular tachycardia was noted for 10 minutes after administration of the 4 mg/kg dose. Increases in systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) occurred after administration of all doses (4, 2, 1, 0.5, and 0.25 mg/kg). Profound hypertension was observed after the 4 mg/kg dose (SAP/DAP, MAP [mmHg] = 291-300/163-213, 218-279). Hemodynamics normalized by 1-2 hours after administration. ACTH and cortisol concentrations increased within 30 minutes of administration of all CoCl2 doses, and cardiac troponin I concentration increased after administration of the 4 and 2 mg/kg doses. CONCLUSIONS AND CLINICAL IMPORTANCE: The degree of hypertension and arrhythmia observed after IV CoCl2 administration raises animal welfare and human safety concerns.

Transcutaneous direct current cardioversion in a foal with lone atrial fibrillation.

There are rare published reports of atrial fibrillation (AF) in foals, all of which are associated with structural heart disease or within the adaptive period of newborns. This report describes a 3-month-old Thoroughbred filly with AF and a structurally normal heart on echocardiography. Medical cardioversion of the foal's AF was attempted with three 20mg/kg doses of quinidine sulfate therapy without success. Timed, transcutaneous, direct current cardioversion was successfully performed using adhesive patches on the midthorax in conjunction with intravenous procainamide at a total dose of 20mg/kg. A normal sinus rhythm was maintained through discharge from the hospital and at recheck 5 months after cardioversion. Transcutaneous direct current cardioversion presents a feasible alternative to quinidine sulfate or transvenous electrical cardioversion in young or lower body weight equids.

Evaluation of Four Diagnostic Tests for Insulin Dysregulation in Adult Light-Breed Horses.

BACKGROUND: Several tests have been evaluated in horses for quantifying insulin dysregulation to support a diagnosis of equine metabolic syndrome. Comparing the performance of these tests in the same horses will provide clarification of their accuracy in the diagnosis of equine insulin dysregulation. OBJECTIVES: The aim of this study was to evaluate the agreement between basal serum insulin concentrations (BIC), the oral sugar test (OST), the combined glucose-insulin test (CGIT), and the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGTT). ANIMALS: Twelve healthy, light-breed horses. METHODS: Randomized, prospective study. Each of the above tests was performed on 12 horses. RESULTS: Minimal model analysis of the FSIGTT was considered the reference standard and classified 7 horses as insulin resistant (IR) and 5 as insulin sensitive (IS). In contrast, BIC and OST assessment using conventional cut-off values classified all horses as IS. Kappa coefficients, measuring agreement among BIC, OST, CGIT, and FSIGTT were poor to fair. Sensitivity of the CGIT (positive phase duration of the glucose curve >45 minutes) was 85.7% and specificity was 40%, whereas CGIT ([insulin]45 >100 µIU/mL) sensitivity and specificity were 28.5% and 100%, respectively. Area under the glucose curve (AUCg0-120 ) was significantly correlated among the OST, CGIT, and FSIGTT, but Bland-Altman method and Lin's concordance coefficient showed a lack of agreement. CONCLUSIONS: Current criteria for diagnosis of insulin resistance using BIC and the OST are highly specific but lack sensitivity. The CGIT displayed better sensitivity and specificity, but modifications may be necessary to improve agreement with minimal model analysis.

Venous thromboembolism rates in patients with lower limb immobilization after Achilles tendon injury are unchanged after the introduction of prophylactic aspirin: audit.

UNLABELLED: ESSENTIALS: We audited venous thromboembolism (VTE) in Achilles injuries after the use of prophylactic aspirin. We audited 218 patients with Achilles injury requiring lower limb immobilization for ≥ 1 week. Fourteen patients (6.4%, 95% CI 3.6% to 10.5%) developed symptomatic and confirmed VTE. The incidence was similar to the 6.3% identified in the same patient group prior to the use of aspirin. BACKGROUND/OBJECTIVE: We report a follow-up audit of the incidence of venous thromboembolism (VTE) in patients requiring lower limb immobilization because of Achilles tendon injury, since the introduction of a policy to routinely prescribe 100 mg of aspirin daily. PATIENTS/METHODS: We studied 218 patients aged 18-65 years who attended the Orthopaedic Assessment Unit at Wellington Hospital between January 2013 and December 2014 with Achilles tendon injury requiring lower limb immobilization for ≥ 1 week. Information on assessment of VTE risk, prescription of aspirin and symptomatic VTE occurring within 70 days of immobilization was obtained and compared with the same information collected with the same method in the same patient group between January 2006 and December 2007, before the policy to routinely prescribe aspirin was introduced. RESULTS: A total of 189 of 218 (93%) patients were prescribed aspirin, as compared with 0.5% previously. Fourteen patients (6.4%, 95% confidence interval 3.6-10.5%) developed symptomatic radiologically confirmed VTE (10 distal deep vein thromboses [DVTs], two proximal DVTs, one pulmonary embolism [PE], and one PE with distal DVT). Aspirin was prescribed to all patients who subsequently developed a VTE; in one of 14, a recognized risk factor was documented. The VTE incidence was similar to the 6.3% identified in the previous audit. CONCLUSION: Lower limb immobilization following Achilles tendon injury confers a high risk of VTE even with aspirin prophylaxis. Consideration should be given to prophylaxis with low molecular weight heparin during lower limb immobilization following Achilles tendon injury, as this has proven efficacy in this clinical situation.

Description of the modes governing the optical transmission through metal gratings.

An analytical model based on a modal expansion method is developed to investigate the optical transmission through metal gratings. This model gives analytical expressions for the transmission as well as for the dispersion relations of the modes responsible for high transmission. These expressions are accurate even for real metals used in the visible - near-infrared wavelength range, where surface plasmon polaritons (SPP's) are excited. The dispersion relations allow the nature of the modes to be assessed. We find that the transmission modes are hybrid between Fabry-Pérot like modes and SPP's. It is also shown that it is important to consider different refractive indices above and below the gratings in order to determine the nature of the hybrid modes. These findings are important as they clarify the nature of the modes responsible for high transmission. It can also be useful as a design tool for metal gratings for various applications.

Observation of enhanced transmission for s-polarized light through a subwavelength slit.

Enhanced optical transmission (EOT) through a single aperture is usually achieved by exciting surface plasmon polaritons with periodic grooves. Surface plasmon polaritons are only excited by p-polarized incident light, i.e. with the electric field perpendicular to the direction of the grooves. The present study experimentally investigates EOT for s-polarized light. A subwavelength slit surrounded on each side by periodic grooves has been fabricated in a gold film and covered by a thin dielectric layer. The excitation of s-polarized dielectric waveguide modes inside the dielectric film strongly increases the s-polarized transmission. A 25 fold increase is measured as compared to the case without the dielectric film. Transmission measurements are compared with a coupled mode method and show good qualitative agreement. Adding a waveguide can improve light transmission through subwavelength apertures, as both s and p-polarization can be efficiently transmitted.

Inexpensive and fast wafer-scale fabrication of nanohole arrays in thin gold films for plasmonics.

In this paper, a fast and inexpensive wafer-scale process for the fabrication of arrays of nanoscale holes in thin gold films for plasmonics is shown. The process combines nanosphere lithography using spin-coated polystyrene beads with a sputter-etching process. This allows the batch fabrication of several 1000 microm(2) large hole arrays in 200 nm thick gold films without the use of an adhesion layer for the gold film. The hole size and lattice period can be tuned independently with this method. This allows tuning of the optical properties of the hole arrays for the desired application. An example application, refractive index sensing, is demonstrated.

The risk of Listeria monocytogenes infection in beef cattle operations.

AIM: To determine the prevalence of Listeria monocytogenes and associated risk factors among beef operations (cow-calf and feedlot) in central and southern California. METHODS AND RESULTS: A repeated cross-sectional study where faecal and environmental samples were collected from 50 operations three times a year at different seasons was carried out. Samples were tested for presence of L. monocytogenes using a combination of enrichment and polymerase chain reaction tests. Data on putative risk factors were also collected. Listeria monocytogenes was detected in faecal samples from cows, calves and other animals on calf-cow operations at proportions of 3.1%, 3.75% and 2.5%, respectively. The organism was detected in 5.3% of cut-grass, 5.3% of soil, 14.3% of irrigation ditches, 3.1% of the ponds and 6.5% of water troughs samples. Listeria monocytogenes was less common in faecal (0.3%) and soil (0.75%) samples collected from feedlots. CONCLUSIONS: Listeria monocytogenes was present at a higher proportion among cow-calf operations than feedlots. There was no significant seasonal variation in the occurrence of this pathogen within the two types of operations. SIGNIFICANCE AND IMPACT OF THE STUDY: If risk mitigation strategies were implemented to reduce the public health risk these should focus in cow-calf operations.

Terahertz quantum cascade lasers based on two-dimensional photonic crystal resonators.

We demonstrate high spectral control from surface emitting THz Quantum Cascade Lasers based on a two-dimensional photonic crystal cavity. The perforated top metallic contact acts as an in plane resonator in a tight double-metal plasmonic waveguide providing a strong optical feedback without needing three-dimensional cavity features. The optical far-field patterns do not exhibit the expected symmetry and the shape of the cavity mode. The difference is attributed to a metal surface plasmon mediated light outcoupling mechanism also responsible for the relatively low extraction efficiency.

Activity of telithromycin and comparators against isolates of Legionella pneumophila collected from patients with community-acquired respiratory tract infections: PROTEKT Years 1-5.

The in-vitro activity of telithromycin and comparator antibacterial agents was determined against clinical isolates of Legionella pneumophila collected in the PROTEKT surveillance study. In total, 133 isolates were collected between 1999 and 2004 from 13 countries (Australia, Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Japan, Portugal, Spain, Sweden and the USA). MICs were determined by broth microdilution. Telithromycin maintained activity between Year 1 (MIC(90) 0.015 mg/L) and Year 5 (MIC(90) 0.03 mg/L), as did the comparator antibacterial agents. Telithromycin appears to be a candidate for coverage of legionellosis in the empirical treatment of community-acquired respiratory tract infection.

Self-collimating photonic crystal polarization beam splitter.

We present theoretical and experimental results of a polarization splitter device that consists of a photonic crystal (PhC) slab, which exhibits a large reflection coefficient for TE and a high transmission coefficient for TM polarization. The slab is embedded in a PhC tile operating in the self-collimation mode. Embedding the polarization-discriminating slab in a PhC with identical lattice symmetry suppresses the in-plane diffraction losses at the PhC-non-PhC interface. The optimization of the PhC-non-PhC interface is thereby decoupled from the optimization of the polarizing function. Transmissions as high as 35% for TM- and 30% for TE-polarized light are reported.

Terahertz photonic crystal quantum cascade lasers.

We combine photonic crystal and quantum cascade band engineering to create an in-plane laser at terahertz frequency. We demonstrate that such photonic crystal lasers strongly improve the performances of terahertz quantum cascade material in terms of threshold current, waveguide losses, emission mode selection, tunability and maximum operation temperature. The laser operates in a slow-light regime between the M saddle point and K band-edge in reciprocal lattice. Coarse frequency control of half of a terahertz is achieved by lithographically tuning the photonic crystal period. Thanks to field assisted gain shift and cavity pulling, the single mode emission is continuously tuned over 30 GHz.

Planar photonic crystals infiltrated with liquid crystals: optical characterization of molecule orientation.

Nematic liquid crystals are infiltrated into InP-based planar photonic crystals. Optical measurements as a function of temperature and polarization are used to study the average director field configuration in the nanometer-size holes: a planar equilibrium state is found.

Confocal microscopy using variable-focal-length microlenses and an optical fiber bundle.

The use of variable-focal-length (VFL) microlenses can provide a way to axially scan the foci across a sample by electronic control. We demonstrate an approach to coupling VFL microlenses individually to a fiber bundle as a way to create a high-throughput aperture array with a controllable aperture pattern. It would potentially be applied in real-time confocal imaging in vivo for biological specimens. The VFL microlenses that we used consist of a liquid-crystal film sandwiched between a pair of conductive substrates for which one has a hole-patterned electrode. One obtains the variation of the focal length by changing the applied voltage. The fiber bundle has been characterized by coupling with both coherent and incoherent light sources. We further demonstrate the use of a VFL microlens array in combination with the fiber bundle to build up a confocal system. The axial response of the confocal system has been measured without mechanical movement of the sample or the objective, and the FWHM is estimated to be approximately 16 microm, with asymmetric sidelobes.

Observation unit treatment of heart failure with nesiritide: results from the proaction trial.

This was a multicenter, randomized, double-blind, placebo-controlled pilot study, evaluating the safety and efficacy of a standard care treatment regimen with the addition of either nesiritide or placebo (SCP) in 237 Emergency Department (ED)/Observation Unit (OU) patients with decompensated heart failure (HF). Efficacy measures included initial admission, length of hospital stay (LOS), and inpatient rehospitalization through 30 days. Compared to the standard care group, patients who also received nesiritide had 11% fewer inpatient hospital admissions at the index ED visit (55% SCP, 49% nesiritide, p = 0.436), and 57% fewer inpatient hospitalizations within 30 days after discharge from the index hospitalization (23% SCP, 10% nesiritide, p = 0.058). The duration of rehospitalization was shorter for nesiritide patients (median LOS 2.5 vs. 6.5 days, p = 0.032). The incidence of symptomatic hypotension was low and did not differ between the groups. This study showed that nesiritide is safe when used in the emergency department, observation units, or similar settings.

Efficacy of telithromycin in community-acquired pneumonia caused by pneumococci with reduced susceptibility to penicillin and/or erythromycin.

BACKGROUND: The efficacy of oral telithromycin was assessed in patients with community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae with reduced susceptibility to penicillin and/or erythromycin. METHODS: Patients with CAP who had received telithromycin 800 mg once daily for 5 or 7-10 days (n = 2,289) in eight phase III clinical trials, or telithromycin 800 mg once daily for 7 days (n = 50) in a phase II study were included in this pooled analysis. Patients with S. pneumoniae as the cause of infection were identified, with particular focus on those infected with strains with reduced susceptibility to penicillin (intermediate, minimal inhibitory concentration (MIC) 0.12-1.0 mg/l; resistant, MIC >or=2.0 mg/l) and/or resistance to erythromycin (MIC >or=1.0 mg/l). Per-protocol clinical and bacteriological outcomes were assessed 7-14 days post-therapy in the phase III studies, and at 7-21 days post-therapy or at the end of therapy in the phase II study. RESULTS: Of the 327 telithromycin-treated patients with S. pneumoniae infection, 61 (19%) were infected with strains with reduced susceptibility to penicillin and/or erythromycin. Clinical cure and bacterial eradication rates in these patients were 91.8% (56/61) and 93.4% (57/61), respectively. Corresponding clinical cure and bacterial eradication rates overall for all isolates of pneumococci were 94.5% (309/327) and 96.0% (314/327), respectively. All isolates with reduced susceptibility to penicillin and/or erythromycin were susceptible to telithromycin (MIC

Design, fabrication and optical characterization of quantum cascade lasers at terahertz frequencies using photonic crystal reflectors.

We designed, fabricated and characterised electrically injected quantum cascade lasers with photonic crystal reflectors emitting at terahertz frequencies (3.75 THz). These in-plane emitting structures display typical threshold current densities of 420 A/cm2 and output powers of up to 2 mW under pulsed excitation. The emission characteristics are shown to be robust, as with increasing current the emission remains singlemode with no drift in wavelength, this results from the narrow reflectivity band of the photonic crystal reflectors.