High-fidelity inference of local impurity profiles in C-2W using Bayesian tomography.

In C-2W (also called "Norman") [1], beam-driven field reversed configuration plasmas embedded in a magnetic mirror are produced and sustained in a steady state. A multi-chord passive Doppler spectroscopy diagnostic provides line-integrated impurity emission measurements near the center plane of the confinement vessel with fast time resolution. The high degree of plasma non-uniformity across optical sightlines can preclude direct fitting of the measured line-integrated spectra. To overcome this challenge, local impurity profiles are inferred using Bayesian tomography, a superior analysis technique based on a complete forward model of the diagnostic. The measured emission of O4+ triplet lines near 278.4 nm is modeled assuming two independent populations: thermal and beam ions. Gaussian processes are used to generate and infer local profiles. The inference incorporates details of the geometrical arrangement of the diagnostic, instrument function, intensity calibration, and a noise model. Markov chain Monte Carlo (MCMC) sampling of the posterior distribution of solutions provides high-fidelity uncertainty estimates. The reconstructed O4+ impurity profiles are consistent with data from other diagnostics and show good agreement with expected physics based on previously developed models of biasing circuit and impurity transport.

Bayesian inference and calibration of magnetic diagnostics.

The magnetic diagnostics across TAE Technologies' compact toroid fusion device include 28 internal and 45 external flux loops that measure poloidal flux and axial field strength, 64 three-axis (radial, toroidal, and axial) Mirnov probes, and 22 internal and external, axial-only Mirnov probes. Imperfect construction, installation, and physical constraints required a Bayesian approach for the calibration process to best account for errors in signals. These errors included flux loops not fitted to a perfect circle due to spatial constraints, Mirnov probes not perfectly aligned against their respective axes, and flux pickup that occurred within the insert (feedthrough) of the Mirnov probes. Our model-based calibration is derived from magnetostatic theory and the circuitry of the sensors. These models predicted outputs that were compared against experimental data. Using a simple least-squares optimization, we were able to predict flux loop data within 1% of relative error. For the Mirnov probes, we utilized Bayesian inference to determine three rotation angles and three amplifier gains. The results of this work not only gave our diagnostic measurements physical meaning, but also act as a safeguard to spot when instruments have malfunctioned, or when there is an error in database maintenance. This paper will go into the details of our calibration procedure, our Bayesian modeling, and the accuracy of our results compared to experimental data.

Derm Dotting: A New Technique That Improves Diagnostic Precision in the Evaluation of Skin Lesions. / Derm dotting: una técnica novedosa para mejorar la precisión diagnóstica de lesiones cutáneas.

Dermoscopy has improved diagnostic precision in the clinical evaluation of complex skin lesions by helping to pinpoint small clinically suspicious areas that are not visible to the naked eye but require histopathologic examination. Derm dotting is a new technique for selectively marking areas of interest to ensure they are examined under a microscope. Left unmarked, suspicious areas might not appear in routinely prepared cross sections or might be difficult to correlate with dermoscopic images. In vivo or ex vivo derm dotting involves the application of nail polish, which, unlike stains, leaves tissues unaltered. Dots can be placed by the dermatologist or laboratory staff during macroscopic preparation of the sample. Derm dotting is a simple, inexpensive technique that any dermatopathology laboratory can quickly adopt to improve diagnostic precision through better dermoscopic-histologic correlation.

Inference of field reversed configuration topology and dynamics during Alfvenic transients.

Active control of field reversed configuration (FRC) devices requires a method to determine the flux surface geometry and dynamic properties of the plasma during both transient and steady-state conditions. The current tomography (CT) method uses Bayesian inference to determine the plasma current density distribution using both the information from magnetic measurements and a physics model in the prior. Here we show that, from the inferred current sources, the FRC topology and its axial stability properties are readily obtained. When Gaussian process priors are used and the forward model is linear, the CT solution involves non-iterative matrix operations and is then ideally suited for deterministic real-time applications. Because no equilibrium assumptions are used in this case, inference of plasma topology and dynamics up to Alfvenic frequencies then becomes possible. Inference results for the C-2U device exhibit self-consistency of motions and forces during Alfvenic transients, as well as good agreement with plasma imaging diagnostics.

Predicting extracapsular involvement in prostate cancer through the tumor contact length and the apparent diffusion coefficient. / Predicción de la extensión extracapsular en el cáncer de próstata mediante la longitud del contacto tumoral y el coeficiente de difusión aparente.

OBJECTIVE: To evaluate the diagnostic performance of the length of the tumor contact with the capsule (LTC) and the apparent diffusion coefficient (ADC) map in the prediction of microscopic extracapsular extension in patients with prostate cancer who are candidates for radical prostatectomy. MATERIAL AND METHODS: We used receiver operating curves to retrospectively study the diagnostic performance of the ADC map and the LTC as predictors of microscopic extracapsular extension in 92 patients with prostate cancer and moderate to high risk who were examined between May 2011 and December 2013. RESULTS: The optimal cutoff for the ADC map was 0.87× 10-3 mm2/s, which yielded an area under the ROC curve of 72% (95% CI: 57%-86%), corresponding to a sensitivity of 83% and a specificity of 61%. The optimal cutoff for the LTC was 17.5mm, which yielded an area under the ROC curve of 74% (95% CI: 61%-87%), corresponding to a sensitivity of 91% and a specificity of 57%. Combining the two criteria improved the diagnostic performance, yielding an area under the ROC curve of 77% (95% CI: 62%-92%), corresponding to a sensitivity of 77% and a specificity of 61%. We elaborated a logistic regression model, obtaining an area under the ROC curve of 82% (95% CI: 73%-93%). CONCLUSIONS: Using quantitative measures improves the diagnostic accuracy of multiparametric magnetic resonance imaging in the staging of prostate cancer. The values of the ADC and LTC were predictors of microscopic extracapsular extension, and the best results were obtained when both values were used in combination.

Post-fundoplication symptoms and complications: Diagnostic approach and treatment. / Síntomas y complicaciones posfunduplicatura: abordaje diagnóstico y tratamiento.

Laparoscopic Nissen fundoplication is currently considered the surgical treatment of choice for gastroesophageal reflux disease (GERD) and its long-term effectiveness is above 90%. Adequate patient selection and the experience of the surgeon are among the predictive factors of good clinical response. However, there can be new, persistent, and recurrent symptoms after the antireflux procedure in up to 30% of the cases. There are numerous causes, but in general, they are due to one or more anatomic abnormalities and esophageal and gastric function alterations. When there are persistent symptoms after the surgical procedure, the surgery should be described as "failed". In the case of a patient that initially manifests symptom control, but the symptoms then reappear, the term "dysfunction" could be used. When symptoms worsen, or when symptoms or clinical situations appear that did not exist before the surgery, this should be considered a "complication". Postoperative dysphagia and dyspeptic symptoms are very frequent and require an integrated approach to determine the best possible treatment. This review details the pathophysiologic aspects, diagnostic approach, and treatment of the symptoms and complications after fundoplication for the management of GERD.

Safety of antitumour necrosis factor treatments in chronic rheumatic diseases: therapy discontinuations related to side effects.

WHAT IS KNOWN AND OBJECTIVE: The appearance of antitumor necrosis factor drugs (ATDs) has been a major advance in the management of these patients. However, due to the immunosuppressive effect of these therapies, side effects that require treatment discontinuations can appear. The purpose of this study was to evaluate the frequency of ATD discontinuation due to adverse drug effects (ADEs) and the influence of different factors such as diagnosis, ATD prescribed and concomitant disease-modifying antirheumatic drugs (DMARDs). METHODS: Observational study from a prospective cohort conducted in a tertiary hospital (1350 beds) in Spain. Data were obtained from the database of the Rheumatology Outpatient Unit of the hospital and patients' clinical files. Included patients had a diagnosis of RA or peripheral or axial SpA (ankylosing spondylitis, psoriatic SpA, non-radiographic SpA, SpA associated with inflammatory bowel disease or reactive arthritis) treated between November 2000 and March 2014 with infliximab (IFX), etanercept (ETN) or adalimumab (ADA). RESULTS AND DISCUSSION: Study cohort included 531 rheumatic patients (282 patients with RA, 53·1%, and 249 patients with SpA, 46·9%). ATDs were discontinued in 62 cases (11·7%) because of ADEs, mainly inmunogenicity and infections (mainly due to infusion reactions, 58·1%, and infections, 19·3%). ATD discontinuation was higher in the group of RA patients compared with SpA (44/282 (15·6%) in RA vs. 18/249 (7·23%) in SpA). The appearance of ADEs that led to drop out was more frequent in patients under IFX therapy (45 (18·6%) with IFX vs. 12 (7·59%) with ETN and 5 (3·81%) with ADA). We observed a significantly increased risk of ADEs when patients received IFX than when ETN or ADA were used (P < 0·001); 444 patients (83·6%) received DMARDs in combination with ATDs. The risk of ATD withdrawal was significantly higher in patients treated with leflunomide as compared to those who do not (OR = 1·984, P < 0·05). WHAT IS NEW AND CONCLUSION: Discontinuation of ATD due to ADEs is relatively frequent and it depends on the diagnosis and ATD administered. The risk of treatment discontinuation is higher in patients diagnosed with RA vs. SpA or treated with IFX (rather than with ETN or ADA). The addition of DMARDs to ATDs increased the frequency of treatment discontinuation, up to three concomitant medications. Leflunomide in combination with an ATD significantly increased the probability of treatment discontinuation due to adverse reactions.

Rapidly-growing squamous cell carcinoma shortly after treatment with ingenol mebutate for actinic keratoses: report of two cases.

Actinic keratoses (AKs) are defined as cutaneous areas of atypical squamous transformation that are regarded as an early step in the continuum of alterations leading from normal skin to invasive and metastatic squamous cell carcinoma (SCC). AKs are classified as precancerous lesions by some authors and in situ SCC by others. The rate of evolution of a given AK to an invasive SCC has been estimated as 0·075-0·096% per lesion per year. These rates are similar to those estimated for gynaecological intraepithelial neoplasia. We describe two cases of SCC with rapid onset that developed after the application of ingenol mebutate gel for the treatment of AKs.

Hair loss in infancy.

Hair diseases represent a significant portion of cases seen by pediatric dermatologists although hair has always been a secondary aspect in pediatricians and dermatologists training, on the erroneous basis that there is not much information extractable from it. Dermatologists are in the enviable situation of being able to study many disorders with simple diagnostic techniques. The hair is easily accessible to examination but, paradoxically, this approach is often disregarded by non-dermatologist. This paper has been written on the purpose of trying to serve in the diagnostic process of daily practice, and trying to help, for example, to distinguish between certain acquired and some genetically determined hair diseases. We will focus on all the data that can be obtained from our patients' hair and try to help on using the messages given by hair for each patient. Quite often it is extremely hard to distinguish between abnormality and normality in neonatal hair aspects. We will specially focus in the most common physiological changes that may mislead to an incorrect diagnosis. Specific treatment for those hair diseases that do have one, and basic general approach to improve the cosmetic appearance of hair, will be also be discussed for those hair disturbances that do not have a specific treatment.

Safety and tolerability of targeted therapies for pulmonary hypertension in children.

The objective of this study is to evaluate the safety and tolerability of the pharmacological treatment of pulmonary hypertension in pediatric patients. It is a retrospective, longitudinal, observational study on pediatric patients undergoing treatment with pulmonary targeted therapies. 63 patients were included (51% male), with a median age of 3.4 years (IQR, 3.6 months-10 years) and a median weight 13 kg (IQR, 6-30 kg). Congenital heart disease was the etiology of pulmonary hypertension in the majority of cases (n = 33) and 28 patients were in NYHA functional class III-IV. The most commonly used drug was sildenafil (n = 79, 56%), followed by bosentan (n = 27, 23%), and a combination of both (n = 14, 41%). 34 patients had adverse reactions (54%) with an incidence rate of 1.02 per patient per year. The most commonly reported reactions were gastrointestinal symptoms (22%) and spontaneous erections (22%) in males. Nine severe adverse reactions (10%) occurred, requiring eight treatment withdrawal and one hospital admission. Treatment with targeted therapies for pulmonary hypertension is safe in the pediatric population. Severe ADRs were uncommon both in monotherapy and in combination therapy. Combination therapy was associated with a higher rate of ADRs. We observed similar survival rates in children receiving sildenafil doses according to the European Medicines Agency (EMA) recommendations or higher.

Cost-effectiveness of recombinant activated factor VII vs. plasma-derived activated prothrombin complex concentrate in the treatment of mild-to-moderate bleeding episodes in patients with severe haemophilia A and inhibitors in Spain.

Several analyses have shown that recombinant activated factor VII (rFVIIa) is a cost-effective intervention compared with plasma-derived activated prothrombin complex concentrate (pd-aPCC) for the on-demand treatment of mild-to-moderate bleeds in haemophilia patients with inhibitors. The aim of the study was to assess the cost-effectiveness of rFVIIa vs. pd-aPCC in the treatment of bleeding episodes in severe haemophilia A patients with inhibitors in Spain. A decision analytic model was designed to evaluate the costs and clinical outcomes of using rFVIIa or pd-aPCC to treat mild-to-moderate joint bleeds in children (≤14 years old) and adults with inhibitors. Data were obtained from a published meta-analysis and a panel of haemophilia experts. The analysis was conducted from the perspective of the Spanish National Healthcare System. One-way sensitivity analyses were performed to assess the impact of model assumptions on study results. In the Treur meta-analysis, rFVIIa resulted in cumulative joint bleed resolution of 88% and 95% after 24 and 36 h, respectively, compared with 62% and 76%, respectively, with pd-aPCC (Treur et al. Haemophilia 2009; 15: 420-36). Here, the mean cost per bleed was estimated at €8473 and €15 579 in children and adults treated with rFVIIa, vs. €8627 and €15 677 in children and adults treated with pd-aPCC. rFVIIa treatment was found to be the dominating option (cheaper and more effective). The one-way sensitivity analysis also confirmed that rFVIIa was less costly than pd-aPCC. The model suggests that rFVIIa is a cost-effective option compared with pd-aPCC for the treatment of mild-to-moderate bleeding episodes in a Spanish setting.

Polar vectors as a method for evaluating the effectiveness of irritable bowel syndrome treatments: an analysis with pinaverium bromide 100mg plus simethicone 300mg po bid.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a disorder characterized by abdominal pain or discomfort associated with changes in bowel habit. Currently there are no objective outcome measures for evaluating the effectiveness of treatments for this disorder. AIMS: To determine the usefulness of a method of analysis that employs polar vectors to evaluate the effectiveness of IBS treatments. METHODS: Data from a Phase IV clinical study with 1677 active IBS-Rome III patients who received 100mg of pinaverium bromide+300mg of simethicone (PB+S) po bid for a period of four weeks were used for the analysis. Using the Bristol Stool Scale as a reference, the consistency and frequency of each type of bowel movement were recorded weekly in a Bristol Matrix (BM) and the data were expressed as polar vectors. RESULTS: The analysis showed a differential response to the PB+S treatment among the IBS subtypes: in reference to the IBS with constipation subtype, the magnitude of the vector increased from 10.2 to 12.5, reaching maximum improvement at two weeks of treatment (p<0.05, Scheffé). In the IBS with diarrhea and mixed IBS subtypes, the magnitude of the vector decreased from 19 to 14 (p<0.05) and from 16.5 to 13 (p<0.05), respectively, with continuous improvement for a period of four weeks. There was no definable vectorial pattern in the unsubtyped IBS group. CONCLUSIONS: Analysis with polar vectors enables treatment response to be measured in different IBS subtypes. All the groups showed improvement with PB+S, but each one had its own characteristic response in relation to vector magnitude and direction. The proposed method can be implemented in clinical studies to evaluate the efficacy of IBS treatments.

Expression and regulation of chemerin during rat pregnancy.

BACKGROUND: Chemerin is an adipocytokine that is expressed in different fat deposits and has been shown to play an important role in adaptive and innate immunity due to its activity as a chemoattractant. Chemerin acts as a ligand for the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been shown to regulate the development and metabolic function of adipocytes, liver and muscle tissue. OBJECTIVE: There is evidence indicating that several adipocytokines play an important role in placenta. This study aimed to investigate the regulation of chemerin in rat and human placentas throughout gestation. DESIGN AND SETTING: Chemerin was examined in rat and human placentas using immunohistochemistry. The chemerin expression pattern in the placenta and adipose tissue of female Sprague Dawley rats on days 12, 16, 19 and 21 of gestation (each of these days represents a group of 12 rats) was determined using TaqMan probe-based quantitative real-time PCR. Rat chemerin serum levels were analyzed with ELISA on days 8, 12, 16, 19 and 21 and compared to virgin controls. RESULTS: Chemerin expression was detected in the cytoplasm of rat placental trophoblastic cells and third trimester human placental cytotrophoblast and Hofbauer's cells. The serum chemerin levels of rats decreased significantly as gestation progressed. Furthermore, placental chemerin mRNA levels rose significantly at day 16 of gestation and decreased significantly towards the end of the gestation period. CONCLUSION: Taken together, this data suggests that chemerin may be an important regulator of maternal-fetal metabolism and metabolic homeostasis during pregnancy.

The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques.

Development of a microbicide that prevents rectal transmission of human immunodeficiency virus (HIV) is a vital component in reducing HIV spread. We recently demonstrated that a formulation of the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan reduced vaginal infection of macaques with simian immunodeficiency virus SIVmac239 with HIV-1(HxB2) reverse transcriptase (SHIV-RT). Herein, we performed the first testing of MIV-150-carrageenan against rectal infection. Rhesus macaques were treated rectally with MIV-150-carrageenan or methyl cellulose (MC) placebo gel up to 4 h prior to rectal challenge with 10³ or 10(4) 50% tissue culture infective doses (TCID50) of SHIV-RT. Infection was assessed by measuring plasma virus RNA as well as T and B cell responses. MIV-150-carrageenan protected all animals challenged with 10³ TCID(50 when gel was applied either 30 min or 4 h prior to challenge, while 100% of the MC-treated animals became infected (n = 4 each; P < 0.03). Partial protection (2 of 4 animals) by MIV-150-carrageenan was observed for rectal challenge with 10-fold more virus applied 4 h after the gel. Sequencing of the RT gene from plasma virus RNA isolated at peak viremia confirmed that both of these animals (like infected MC controls) were infected with wild-type virus. Infection correlated with the development of SIV-specific T and B cell responses. MIV-150 was detected in the rectal fluids and tissues 4 h after gel application but was not detected in the blood at any time (0.5 to 24 h). These data are promising for the development of NNRTI-containing gels to prevent rectal HIV transmission.

Application of the analysis of serum antibodies (immunoglobulins M and G) to estimate the seroprevalence of ovine oestrosis and to evaluate the effect of chemotherapy.

The analysis of immunoglobulin (Ig) M and IgG serum isotypes as indicators of the presence of Oestrus ovis developmental stages was carried out. A serological survey to discover the seasonal variations in the prevalence of oestrosis in sheep from an oceanic climate area was developed. Six hundred and sixty-nine blood samples were analyzed for the presence of IgM and IgG using an enzyme-linked immunosorbent assay and O. ovis second-stage larvae excretory/secretory antigens. In addition, the effect of an ivermectin-based treatment on the humoral immune response was measured. The percentage of positive animals was 54% for IgM and 55% for IgG. The highest percentages of sheep positive to IgM were recorded in the winter and to IgG in the summer. No animals positive to IgM were detected in the ivermectin-treated sheep. These results seem to underline that oestrosis is a parasitic disease to keep watch for in regions with an oceanic climate. A noninvasive evaluation of the success of chemotherapy seems possible by analyzing the serum IgM response.

Diffraction by a circular aperture: an application of the vectorial theory of Huygens's principle in the near field.

A vectorial theory that brings new insight into the nature of diffraction is used to obtain mathematical expressions that evaluate diffraction patterns in the near field. The equations allow us to discriminate between the contributions of the vectorial and the scalar approaches. In the near field we studied the pattern of light diffracted through a circular aperture, and it was proved that the vectorial approach is significant in a region very near the circular aperture. In spite of the obvious differences between the circular aperture and other obstacles, the present theory may also be used with other geometries.