Paraneoplastic syndrome of arthropathies as presenting sign for non-small cell lung cancer.

The aim of this study is to showcase an example of paraneoplastic syndrome, so other healthcare providers can be aware of early NSCLC manifestations. This is also important so providers do not dismiss review of symptoms that may not seem pertinent.

Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

The first pulse of the extremely bright GRB 130427A: a test lab for synchrotron shocks.

Gamma-ray burst (GRB) 130427A is one of the most energetic GRBs ever observed. The initial pulse up to 2.5 seconds is possibly the brightest well-isolated pulse observed to date. A fine time resolution spectral analysis shows power-law decays of the peak energy from the onset of the pulse, consistent with models of internal synchrotron shock pulses. However, a strongly correlated power-law behavior is observed between the luminosity and the spectral peak energy that is inconsistent with curvature effects arising in the relativistic outflow. It is difficult for any of the existing models to account for all of the observed spectral and temporal behaviors simultaneously.

Fermi-LAT observations of the gamma-ray burst GRB 130427A.

The observations of the exceptionally bright gamma-ray burst (GRB) 130427A by the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope provide constraints on the nature of these unique astrophysical sources. GRB 130427A had the largest fluence, highest-energy photon (95 GeV), longest γ-ray duration (20 hours), and one of the largest isotropic energy releases ever observed from a GRB. Temporal and spectral analyses of GRB 130427A challenge the widely accepted model that the nonthermal high-energy emission in the afterglow phase of GRBs is synchrotron emission radiated by electrons accelerated at an external shock.

Forecasting Hotspots-A Predictive Analytics Approach.

Current visual analytics systems provide users with the means to explore trends in their data. Linked views and interactive displays provide insight into correlations among people, events, and places in space and time. Analysts search for events of interest through statistical tools linked to visual displays, drill down into the data, and form hypotheses based upon the available information. However, current systems stop short of predicting events. In spatiotemporal data, analysts are searching for regions of space and time with unusually high incidences of events (hotspots). In the cases where hotspots are found, analysts would like to predict how these regions may grow in order to plan resource allocation and preventative measures. Furthermore, analysts would also like to predict where future hotspots may occur. To facilitate such forecasting, we have created a predictive visual analytics toolkit that provides analysts with linked spatiotemporal and statistical analytic views. Our system models spatiotemporal events through the combination of kernel density estimation for event distribution and seasonal trend decomposition by loess smoothing for temporal predictions. We provide analysts with estimates of error in our modeling, along with spatial and temporal alerts to indicate the occurrence of statistically significant hotspots. Spatial data are distributed based on a modeling of previous event locations, thereby maintaining a temporal coherence with past events. Such tools allow analysts to perform real-time hypothesis testing, plan intervention strategies, and allocate resources to correspond to perceived threats.

Multiclass detection of cells in multicontrast composite images.

In this paper, we describe a framework for multiclass cell detection in composite images consisting of images obtained with three different contrast methods for transmitted light illumination (referred to as multicontrast composite images). Compared to previous multiclass cell detection results [1], the use of multicontrast composite images was found to improve the detection accuracy by introducing more discriminatory information into the system. Preprocessing multicontrast composite images with Kernel PCA was found to be superior to traditional linear PCA preprocessing, especially in difficult classification scenarios where high-order nonlinear correlations are expected to be important. Systematic study of our approach under different overlap conditions suggests that it possesses sufficient speed and accuracy for use in some practical systems.

High-dose glycine treatment of refractory obsessive-compulsive disorder and body dysmorphic disorder in a 5-year period.

This paper describes an individual who was diagnosed with obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) at age 17 when education was discontinued. By age 19, he was housebound without social contacts except for parents. Adequate trials of three selective serotonin reuptake inhibitors, two with atypical neuroleptics, were ineffective. Major exacerbations following ear infections involving Group A beta-hemolytic streptococcus at ages 19 and 20 led to intravenous immune globulin therapy, which was also ineffective. At age 22, another severe exacerbation followed antibiotic treatment for H. pylori. This led to a hypothesis that postulates deficient signal transduction by the N-methyl-D-aspartate receptor (NMDAR). Treatment with glycine, an NMDAR coagonist, over 5 years led to robust reduction of OCD/BDD signs and symptoms except for partial relapses during treatment cessation. Education and social life were resumed and evidence suggests improved cognition. Our findings motivate further study of glycine treatment of OCD and BDD.

Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults.

BACKGROUND: Recent preclinical findings, case reports and non-blinded studies have suggested that glutamatergic interventions may be efficacious for Obsessive-Compulsive Disorder (OCD). METHODS: We enrolled 24 adult outpatients with OCD on stabilized treatment regimens in a double-blind trial of adjunctive glycine, an NMDA glutamate receptor agonist. Participants were randomly assigned 1:1 to either placebo or glycine titrated to 60g/day, with follow-up visits scheduled at 4, 8 and 12 weeks. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the principal outcome measure. RESULTS: Regimen non-adherence, principally related to complaints about the taste and/or nausea, resulted in only 14 individuals who were evaluable by predetermined criteria. Those receiving glycine (n=5) experienced a mean decrease of 6.04 points in Y-BOCS score, compared with a 1.00 point decrease for those receiving placebo (n=9). Using a hierarchical linear model, compared with placebo, individuals who received glycine had an average 0.82 decrease in Y-BOCS score for each week they remained in the study, not quite reaching statistical significance (p=0.053). Two of those receiving glycine were responders, versus none receiving placebo (p=0.11, ns, Fisher exact). Despite the dropouts, two participants were known to have subsequently continued taking glycine through their regular treating psychiatrist for over a year. CONCLUSIONS: The glycine condition approached efficacy for treatment of OCD in this study, with the high dropout rate related to problems with palatability and small sample size the principal caveats. This may indicate a new strategy for treatment of OCD, although confirmatory studies are clearly needed. (ClinicalTrials.gov NCT00405535.).

Automatic detection of unstained viable cells in bright field images using a support vector machine with an improved training procedure.

Detection of unstained viable cells in bright field images is an inherently difficult task due to the immense variability of cell appearance. Traditionally, it has required human observers. However, in high-throughput robotic systems, an automatic procedure is essential. In this paper, we formulate viable cell detection as a supervised, binary pattern recognition problem and show that a support vector machine (SVM) with an improved training algorithm provides highly effective cell identification. In the case of cell detection, the binary classification problem generates two classes, one of which is much larger than the other. In addition, the total number of samples is extremely large. This combination represents a difficult problem for SVMs. We solved this problem with an iterative training procedure ("Compensatory Iterative Sample Selection", CISS). This procedure, which was systematically studied under various class size ratios and overlap conditions, was found to outperform several commonly used methods, primarily owing to its ability to choose the most representative samples for the decision boundary. Its speed and accuracy are sufficient for use in a practical system.

A new preprocessing approach for cell recognition.

In this paper, we describe a novel strategy for combining fisher's linear discriminant (FLD) preprocessing with a feedforward neural network to classify cultured cells in bright field images. This technique was applied to various experimental scenarios utilizing different imaging environments, and the results were compared with those for the traditional principal component analysis (PCA) preprocessing. Our FLD preprocessing was shown to be more effective than PCA due in large part to the fact that FLD maximizes the ratio of between-class to within-class scatter. The new cell recognition algorithm with FLD preprocessing improves accuracy while the speed is suitable for practical applications.

Control of the pleural space after pneumonectomy.

The authors believe that most patients who undergo pneumonectomy do not require drainage of the postpneumonectomy space. Needle or catheter aspiration is simple and usually adequate. In cases in which significant bleeding, rapid pleural fluid accumulation, or contamination is expected, however, drainage of the space is recommended. If drainage is used, the tube probably should be connected to a balanced drainage system to ensure proper physiologic positioning of the mediastinum during the critical immediate postoperative period.

Pulmonary metastasectomy for metastatic malignant melanoma.

Melanoma is the most deadly of skin cancers, and metastatic disease most commonly first appears in the lungs. Because most patients with early metastatic pulmonary disease are asymptomatic, routine screening with chest radiographs is the most cost-effective method of discovery. The therapy for pulmonary metastatic melanoma has drastically changed over the years. Even today there is no curative immunotherapy or chemotherapy available. The long-term overall survival for these patients is still very poor, but early detection and surgery offers the only hope for control in a small number of patients.

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Targeted intervention to improve compliance in an urban hemodialysis population.

Noncompliance impacts the successful delivery of care to the "urban" ESRD population. It is our belief that noncompliance can be an extension of the dysfunctional coping mechanisms of patients who lack adequate psychosocial support. In this article, we have described a pilot program providing on-site, targeted intervention for patients identified at increased risk for poor clinical outcomes, based on failure to comply with the prescribed dialysis treatment prescription. This collaboration between our "nephrology practice," an outpatient "HD facility," and a "C-L psychiatry service" has resulted in extremely low no-show rates in an urban dialysis population. We have also discovered an opportunity for reducing hospitalizations. Targeted intervention can improve compliance and prove to be cost effective.

Pertechnetate scintigraphy in primary congenital hypothyroidism.

UNLABELLED: Primary congenital hypothyroidism (PCH) is currently detected effectively by heel-stick screening. When elevated thyrotropin (TSH) and/or decreased T4 are found in the blood of neonates, they are recalled, values are confirmed in venous blood and thyroxine replacement therapy (TRT) is immediately instituted, thus cretinism or severe retardation is prevented. However, in a significant percentage of neonates with abnormal blood levels of T4 or TSH, the disorder is transient. To help determine the exact cause of PCH and the possibility of transient PCH, pinhole thyroid imaging is performed 30 min after an intravenous injection of 18.5 MBq (500 microCi) 99mTc-pertechnetate (TcPT). Patients with a nonvisualized gland or patients with images suggesting dyshormonogenesis are reevaluated at age 3-4 y to exclude transient PCH. METHODS: To define the role of TcPT imaging in determining the exact etiology of PCH and the possibility of its being transient, we reviewed data from 103 neonates with PCH who had scintigraphy in our laboratory between 1970 and 1996 and we correlated the results with clinical outcome. RESULTS: Four patterns of thyroid scintigrams were recognized and these determined patient classification: (a) normal in 7 patients with false-positive heel-stick screening but normal venous blood hormone levels; (b) hypoplasia-ectopia in 32 patients requiring lifelong TRT; (c) nonvisualization in 35 patients-32 with agenesis requiring lifelong TRT and 3 with fetal thyroid suppression by maternal antibodies whose TRT was discontinued at a later age; and (d) dyshormonogenesis (markedly increased TcPT concentration) in 29 patients-25 with permanent PCH requiring lifelong TRT and 4 with transient PCH in whom TRT was discontinued. Of the 25 patients with dyshormonogenesis, 12 belonged to five families with two or three siblings having the same disorder. CONCLUSION: TcPT thyroid scintigraphy in the neonate with PCH provides a more specific diagnosis, is useful for selecting patients for re-evaluation to uncover transient PCH and discontinue TRT and defines dyshormonogenesis, which is familial and requires genetic counseling. It is also cost-effective.

Kenny-Caffey syndrome and microorchidism.

We report on two adolescent boys with Kenny-Caffey syndrome and microorchidism. The first patient had elevated levels of serum follicle-stimulating hormone, but normal levels of luteinizing hormone and testosterone. There was no evidence of a microdeletion of the Y chromosome. The second patient had Leydig cell hyperplasia with normal seminiferous tubules and spermatogenesis, and normal pituitary histologic findings at autopsy. The presence of microorchidism in these patients confirms the previous observations and suggests subfertility, but does not fully clarify the pathogenesis.

Growth hormone receptor mutations in children with idiopathic short stature.

Homozygous or compound heterozygous mutations in the GH receptor (GHR) gene result in GH insensitivity syndrome. Previous reports have shown that some heterozygous mutations may induce a partial insensitivity to GH, but others appear to have limited effect on growth. To investigate further these observations, we analyzed the GHR gene in 17 subjects with idiopathic short stature (ISS). All subjects had a height 2 SD or more below the mean and/or abnormal growth velocity. In addition, serum GH levels were 10 ng/mL or more and insulin-like growth factor I levels were normal or low. A novel heterozygous mutation resulting in a valine to isoleucine change (V144I) in exon 6 in the extracellular domain was found in one subject. His mother and one brother had significant short stature and also had the identical mutation. Affected family members also had a polymorphism in exon 6 of the GHR gene, which has been present in other subjects who had short stature and heterozygous mutations of the GHR gene. The other subjects with ISS had normal GHR genes. However, eight subjects had neutral polymorphisms distributed throughout the GHR locus. Accumulating evidence suggests that GHR gene mutations account for up to 5% of all ISS patients. These mutations should be considered when other causes of short stature have been eliminated.