CAP Class Research Articles

Diagnostics of allergic rhinitis under dupilumab therapy

BackgroundAllergic rhinits is a prevalent condition, affecting a substantial proportion of the population. This study investigates the impact of ongoing biologic therapy, specifically with Dupilumab, on allergy diagnostics in patients with allergic rhinits.MethodsVarious tests, including the Skin Prick Test, serum IgE levels and Allergy Screening Panels, were examined for their effectiveness in detecting sensitizations during biologic treatment.ResultsThe results indicate a significant decline in total IgE levels following biologic therapy initiation, aligning with previous findings on Dupilumab's inhibitory effects on IL-4 and IL-13. However, the specific IgE to total IgE ratio for major allergens was not significantly reduced. Comparing diagnostic tools, the Skin Prick Test demonstrates an impressive retention rate of sensitizations (98%) during Dupilumab treatment, outperforming the Allergy Screening Panel, which shows a 75% detection rate. Notably, the panel displays limitations in capturing lower sensitization levels.ConclusionIn summary, this study underscores that, despite the influence of biologic therapy on certain markers, standard allergy tests remain viable while emphasizing the importance of considering specific IgE levels rather than relying solely on CAP classes. The Skin Prick Test in particular proves to be a reliable tool for identifying sensitizations during Dupilumab treatment. The results offer valuable guidance for the diagnostic management of Allergic rhinits in individuals subjected to Dupilumab treatment.

Structural basis of dual activation of cell division by the actinobacterial transcription factors WhiA and WhiB

Studies of transcriptional initiation in different bacterial clades reveal diverse molecular mechanisms regulating this first step in gene expression. The WhiA and WhiB factors are both required to express cell division genes in Actinobacteria and are essential in notable pathogens such as Mycobacterium tuberculosis. The WhiA/B regulons and binding sites have been elucidated in Streptomyces venezuelae (Sven), where they coordinate to activate sporulation septation. However, how these factors cooperate at the molecular level is not understood. Here we present cryoelectron microscopy structures of Sven transcriptional regulatory complexes comprising RNA polymerase (RNAP) σA-holoenzyme and WhiA and WhiB, in complex with the WhiA/B target promoter sepX. These structures reveal that WhiB binds to domain 4 of σA (σA4) of the σA-holoenzyme, bridging an interaction with WhiA while making non-specific contacts with the DNA upstream of the -35 core promoter element. The N-terminal homing endonuclease-like domain of WhiA interacts with WhiB, while the WhiA C-terminal domain (WhiA-CTD) makes base-specific contacts with the conserved WhiA GACAC motif. Notably, the structure of the WhiA-CTD and its interactions with the WhiA motif are strikingly similar to those observed between σA4 housekeeping σ-factors and the -35 promoter element, suggesting an evolutionary relationship. Structure-guided mutagenesis designed to disrupt these protein-DNA interactions reduces or abolishes developmental cell division in Sven, confirming their significance. Finally, we compare the architecture of the WhiA/B σA-holoenzyme promoter complex with the unrelated but model CAP Class I and Class II complexes, showing that WhiA/WhiB represent a new mechanism in bacterial transcriptional activation.

Nonlinear Class Size Effects on Cognitive and Noncognitive Development of Young Children

We estimate the nonlinear impact of class size on student achievement by exploiting regulations that cap class size at 20 students per class in kindergarten. Based on student-level information from a previously unexploited and unique large-scale census survey of kindergarten students, this study provides clear evidence of the nonlinearity of class size effects on development measures. While the effects are largest on cognitive development, class size reductions also improve noncognitive skills for children living in disadvantaged areas. These findings suggest that sizeable class size reductions targeted at disadvantaged areas would achieve better results than a marginal reduction across the board.

Recognition of COVID-19 from CT Scans Using Two-Stage Deep-Learning-Based Approach: CNR-IEMN.

Since the appearance of the COVID-19 pandemic (at the end of 2019, Wuhan, China), the recognition of COVID-19 with medical imaging has become an active research topic for the machine learning and computer vision community. This paper is based on the results obtained from the 2021 COVID-19 SPGC challenge, which aims to classify volumetric CT scans into normal, COVID-19, or community-acquired pneumonia (Cap) classes. To this end, we proposed a deep-learning-based approach (CNR-IEMN) that consists of two main stages. In the first stage, we trained four deep learning architectures with a multi-tasks strategy for slice-level classification. In the second stage, we used the previously trained models with an XG-boost classifier to classify the whole CT scan into normal, COVID-19, or Cap classes. Our approach achieved a good result on the validation set, with an overall accuracy of 87.75% and 96.36%, 52.63%, and 95.83% sensitivities for COVID-19, Cap, and normal, respectively. On the other hand, our approach achieved fifth place on the three test datasets of SPGC in the COVID-19 challenge, where our approach achieved the best result for COVID-19 sensitivity. In addition, our approach achieved second place on two of the three testing sets.

Reduced Exhaled Breath Condensate pH and Severity of Allergic Sensitization Predict School Age Asthma

We previously reported that deaerated breath condensate pH (dEBC pH) can identify preschool children with recurrent wheezing at high asthma risk. To assess the ability of preschool dEBC pH to predict asthma risk at school age. Children of the baseline cohort were recontacted for follow-up. Asthma diagnosis at school age was evaluated according to Global Initiative for Asthma recommendations in 135 children who at baseline had been classified into the following groups: (asymptomatic) atopic wheezers (n= 30), (asymptomatic) nonatopic wheezers (n= 57), allergic rhinitis only (n= 14), and healthy controls (n= 34). All (100%) former atopic wheezers, 12 (21%) of nonatopic wheezers, 2 (14%) of allergic rhinitis group, and 1 (3%) of healthy controls had developed asthma at follow-up. Among all children with baseline wheezing, baseline dEBC pH predicted asthma at follow-up with an area under the receiver operating characteristic curve (AUC) of 0.72 (sensitivity, 0.67; specificity, 0.76; at pH 7.83). Combining pH and Capacity class (CAP) led to substantial gain in sensitivity (0.96) and negative predictive value (NPV, 0.94). Additional clinical information (Asthma Predictive Index, family atopy, family asthma, and inhaled corticosteroids) further increased the potential to predict asthma (AUC, 0.94) and raised sensitivity (0.98) and NPV (0.97) to nearly perfect values. Our findings suggest (1) that dEBC pH combined with CAP class may serve as highly sensitive, noninvasive marker for the early detection of young asymptomatic preschool children with increased asthma risk, and (2) the need for additional biomarkers with high specificity to optimize early risk stratification in this clinically challenging scenario.

Development of atopic sensitization in Finnish and Estonian children: A latent class analysis in a multicenter cohort

The prevalence of atopy is associated with a Western lifestyle, as shown by studies comparing neighboring regions with different socioeconomic backgrounds. Atopy might reflect various conditions differing in their susceptibility to environmental factors. We sought to define phenotypes of atopic sensitization in early childhood and examine their association with allergic diseases and hereditary background in Finland and Estonia. The analysis included 1603 Finnish and 1657 Estonian children from the DIABIMMUNE multicenter young children cohort. Specific IgE levels were measured at age 3, 4, and 5years, respectively, and categorized into 3 CAP classes. Latent class analysis was performed with the statistical software package poLCA in R software. Both populations differed in terms of socioeconomic status and environmental determinants, such as pet ownership, farm-related exposure, time spent playing outdoors, and prevalence of allergic diseases (all P<.001). Nevertheless, we found similar latent classes in both populations: an unsensitized class, a food class, 2 inhalant classes differentiating between seasonal and perennial aeroallergens, and a severe atopy class. The latter was characterized by high total and specific IgE levels and strongly associated with wheeze (odds ratio [OR], 5.64 [95% CI, 3.07-10.52] and 4.56 [95% CI, 2.35-8.52]), allergic rhinitis (OR, 22.4 [95% CI, 11.67-44.54] and 13.97 [95% CI, 7.33-26.4]), and atopic eczema (OR, 9.39 [95% CI, 4.9-19.3] and 9.5 [95% CI, 5.2-17.5] for Finland and Estonia, respectively). Environmental differences were reflected in the larger seasonal inhalant atopy class in Finland, although composition of classes was comparable between countries. Despite profound differences in environmental exposures, there might exist genuine patterns of atopic sensitization. The distribution of these patterns might determine the contribution of atopic sensitization to disease onset.

Allergen content in German cockroach extracts and sensitization profiles to a new expanded set of cockroach allergens determine in vitro extract potency for IgE reactivity

Cockroach allergens are an important cause of IgE-mediated sensitization in inner-city asthmatic patients. However, cockroach extracts used for diagnosis and immunotherapy are not standardized. We sought to determine the allergen content of nonstandardized German cockroach extracts and the levels of sensitization to an expanded set of cockroach allergens as determinants of invitro extract potency for IgE reactivity. Twelve German cockroach extracts were compared for allergen content and potency of IgE reactivity. Bla g 1, Bla g 2, and Bla g 5 were measured by using immunoassays. IgE antibody levels to 8 purified recombinant allergens from groups 1, 2, 4, 5, 6, 7, 9, and 11 were measured by using ImmunoCAP. IgE antibody binding inhibition assays were performed to assess extract invitro potencies (concentration inhibiting 30% of the total IgE antibody-binding inhibition) relative to an arbitrarily selected reference extract in 5 patients with cockroach allergy. Allergen levels were highly variable. Three new major allergens (groups 6, 9, and 11), were identified among highly cockroach-sensitized subjects (CAP class≥3). Sensitization profiles were unique per subject without immunodominant allergens. The sum of IgE to 8 allergen components showed a good correlation with cockroach-specific IgE levels (r=0.88, P<.001). Invitro potencies varied among different extracts per subject and among subjects for each extract. The invitro potency of German cockroach extracts for IgE reactivity depends on allergen content and allergen-specific IgE titers of patients with cockroach allergy. These factors are relevant for selection of potent extracts to be used for immunotherapy and for the design and interpretation of data from immunotherapy trials.

Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of Recombinant Allergen-Based IgE Serology

Background:Dermatophagoides pteronyssinus is one of the most important perennial allergen sources worldwide. Molecular diagnostics using the commercially available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do not detect house dust mite (HDM) sensitization in a number of cases when used alone. The objective was to evaluate the IgE reactivity profiles of these patients using an experimental immunoassay biochip. Methods: Sera of HDM-allergic patients (positive skin prick test, CAP class ≥1 for allergen extract, and positive intranasal provocation) were tested for IgE antibodies against Der p 1, Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively tested sera were examined by an experimental chip containing 13 microarrayed HDM allergens. Results: Of 97 patients tested, 16 showed negative results to Der p 1, Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients monosensitized to Der p 23, and 11 patients were negative for all HDM MeDALL chip components. Seven sera were available for further testing, and 3 of them showed IgE reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 125I-labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of the 11 patients were <3.9 kU/l. Conclusions: Recombinant allergen-based IgE serology is of great value when conventional IgE diagnostics fails. Der p 23 is an important HDM allergen, especially when major allergens are negative. Therefore, it would be desirable to have Der p 23 commercially available. Further research concerning the prevalence and clinical significance of different HDM allergens is needed.

Buckling Capacity Curves for Steel Spherical Shells Loaded by the External Pressure

Assessment of buckling resistance of pressurised spherical cap is not an easy task. There exist two different approaches which allow to achieve this goal. The first approach involves performing advanced numerical analyses in which material and geometrical nonlinearities would be taken into account as well as considering the worst imperfections of the defined amplitude. This kind of analysis is customarily called GMNIA and is carried out by means of the computer software based on FEM. The other, comparatively easier approach, relies on the utilisation of earlier prepared procedures which enable determination of the critical resistance pRcr, the plastic resistance pRpl and buckling parameters a, b, h, l 0 needed to the definition of the standard buckling resistance curve. The determination of the buckling capacity curve for the particular class of spherical caps is the principal goal of this work. The method of determination of the critical pressure and the plastic resistance were described by the authors in [1] whereas the worst imperfection mode for the considered class of spherical shells was found in [2]. The determination of buckling parameters defining the buckling capacity curve for the whole class of shells is more complicated task. For this reason the authors focused their attention on spherical steel caps with the radius to thickness ratio of R/t = 500, the semi angle j = 30o and the boundary condition BC2 (the clamped supporting edge). Taking into account all imperfection forms considered in [2] and different amplitudes expressed by the multiple of the shell thickness, sets of buckling parameters defining the capacity curve were determined. These parameters were determined by the methods proposed by Rotter in [3] and [4] where the method of determination of the exponent h by means of additional parameter k was presented. As a result of the performed analyses the standard capacity curves for all considered imperfection modes and amplitudes 0.5t, 1.0t, 1.5t were obtained. Obtained capacity curves were compared with the recommendations for different fabrication quality classes formulated in [5].

Oral Allergy Syndrome Following Soy Milk Ingestion in Patients with Birch Pollen Allergy

Persons allergic to birch pollen often report oral and pharyngeal hypersensitivity to fruit and vegetables, due to immunological cross-reactivity between pollen and foods. This phenomenon is referred to as the oral allergy syndrome (GAS). Such cross-reactive antigen reactions mainly involve Bet v 1, which is the major birch-pollen allergen, and partially involve birch-pollen profilin Bet v 2. Soybean contains Bet v 1-related antigen (Gly m 4), and soy milk often causes the OAS with severe symptoms such as precordial and abdominal burning sensation because soy milk undergoes little denaturation, and this water-soluble liquid is consumed by most people rather quickly. We evaluated the frequency of the oAS after ingestion of soymilk and examined IgE antibodies to various allergens. A total of 167 patients [122 women, 45 men; age range, 4-72 years (mean age, 32 years)], who had experienced GAS episodes and had IgE birch--pollen antibodies, were interviewed. Using the CAP system, we examined IgE antibodies to birch pollen and other allergens. Of 167 patients, 161 were examined for IgE antibodies to Bet v 1, Bet v 2, Gly m 4, and soybean. We evaluated the frequency of the GAS after soy milk ingestion based on reports by GAS patients with birch pollen allergy, and evaluated the positive rates of some of the IgE antibodies. Among the 167 patients with birch-pollen allergy and GAS on ingestion of any of the foods, there were 16 cases (10%) with OAS following soy milk ingestion. In addition, the foods that caused OAS most often were apples (123 cases, 74%), peaches (67%), and cherries (55%), followed by pears (37%) and kiwi (37%). A higher CAP class for birch pollen, Bet v 1, Gly m 4, and soybean was associated with a higher prevalence of OAS to soy milk. Of 15 patients who had GAS on ingestion of soy milk and had birch-pollen allergy, 47% (7cases) were CAP class 1 for soybean and only 7% (case) was CAP class c2, whereas 93% (14cases) were CAP class 1 for Gly m 4, and 87% (3cases) were CAP class ≥ 2 for Gly m 4. Among the birch-pollen allergic OAS patients, 10% had the OAS on ingestion of soy milk, and among these with birch-pollen allergy and the OAS on ingestion of soy milk, the positive rate for soy milk CAP was low, whereas that for Gly m 4 CAP was high.

Sleep cyclic alternating pattern in otherwise healthy overweight school-age children.

To compare sleep microstructure (cyclic alternating pattern, CAP) characteristics in otherwise healthy overweight (OW) and normal weight (NW) children. Polysomnographic cross-sectional study. Sleep laboratory. Fifty-eight (26 NW and 32 OW) 10-year-old children. N/A. Participants were part of a longitudinal study beginning in infancy and free of sleep disorders. Groups were based on body-mass index (BMI) z-score. From polysomnographic overnight recordings, sleep-waking states were scored according to international criteria. CAP analysis was performed visually during NREM sleep. Conventional sleep parameters were similar between groups. BMI was positively related to CAP rate and CAP sequences but inversely related to CAP B phase duration. Differences between groups were confined to slow-wave sleep (SWS), with OW children showing higher CAP rate, CAP cycles, and CAP A1 number and index and shorter CAP cycles and B phase duration. They also showed more CAP class intervals shorter than 30 s, and a suggestive trend for fewer intervals longer than 30 s. Cyclic alternating pattern characteristics in children related to nutritional status and were altered in overweight subjects during slow-wave sleep. We suggest that the more frequent oscillatory pattern of electroencephalographic slow activity in overweight subjects might reflect less stable slow-wave sleep episodes.

Serial measurements of exhaled nitric oxide at work and at home: a new tool for the diagnosis of occupational asthma.

Whereas serial measurements of lung function at work and at home are a well-known diagnostic tool for the diagnosis of occupational asthma (OA), little is known about the serial measurements of non-invasive parameters such as exhaled nitric oxide (eNO). A 51-year-old baker with variable shortness of breath without relation to work was examined for suspected OA. Skin prick test showed weak sensitizations to wheat and rye flour (without sensitizations to environmental allergens) that were corroborated by in vitro testing (CAP class 3). Baseline FEV1 of 58% predicted and a decrease of forced expiratory volume in 1 s (FEV1) after placebo (sugar powder) of 17% did not allow inhalational challenge testing. The patient performed daily measurements of FEV1 and eNO for about a month during a holiday at home and at work. Whereas symptoms and FEV1 did not show differences between holidays and work periods, eNO showed a clear increase from below 10 ppb to a maximum of 75 ppb. A diagnosis of baker's asthma was made, and the patient quit his job immediately after medical advice. A year afterwards, the patient was still taking asthma medication, but his symptoms had improved, FEV1 had increased to 73% predicted, and eNO was 25 ppb. We conclude that serial measurements of eNO at home and at work may be a useful tool for the diagnosis of OA.

Intrinsic invariants of cross caps

It is classically known that generic smooth maps of R^2 into R^3 admit only cross cap singularities. This suggests that the class of cross caps might be an important object in differential geometry. We show that the standard cross cap (u,uv,v^2) has non-trivial isometric deformations with infinite dimensional freedom. Since there are several geometric invariants for cross caps, the existence of isometric deformations suggests that one can ask which invariants of cross caps are intrinsic. In this paper, we show that there are three fundamental intrinsic invariants for cross caps. The existence of extrinsic invariants is also shown.

Anisakis Allergy Component-Resolved Diagnosis: Clinical and Immunologic Differences between Patients from Italy and Spain

Background:Anisakissimplex is the main organism responsible for the zoonotic disease anisakiasis which follows the ingestion of live larvae present in raw or undercooked marine fish. Clinical features include severe epigastric pain, frequently accompanied by severe allergic reactions. We investigated the prevalence of immunoglobulin E (IgE) specific for 5 Anisakis allergens in Italian patients sensitized or allergic to the parasite. The results were compared with those obtained previously in a similar Spanish population. Patients and Methods: We conducted a descriptive, cross-sectional validation study. Asymptomatic Anisakis-sensitized subjects (15 Italian and 17 Spanish) and Anisakis allergic-patients (42 Italian and 35 Spanish) were studied by ImmunoCAP, Western-blotting with nAni s 4 and dot-blotting with rAni s 1, rAni s 5, rAni s 9 and rAni s 10. Results:Anisakis IgE CAP classes 1 or 2 were associated with a high probability of asymptomatic sensitization (66.7%) while CAP classes 4 or above, were associated with a very high probability of allergy to Anisakis (95.2%). The most frequently detected allergen among Italian and Spanish allergic patients was Ani s 1. All of the Spanish patients versus 76.2% of the Italian patients recognized at least one of the allergens tested. Patients suffering from gastrointestinal symptoms only were significantly more frequent among the Italians whereas the Spanish presented more frequently with urticaria, angioedema or anaphylaxis. Conclusions:Anisakis hypersensitivity shows different immunological patterns in different European countries. Allergen component diagnosis might help us to better understand this complex entity. Anisakis-specific IgE levels may have moderate prognostic significance.

IgE-Mediated Hypersensitivity Reactions to Cannabis in Laboratory Personnel

Background: There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. Objective: We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. Methods: Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. Results: Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. Conclusions: Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish.

Correlation of Routine Examinations for the Diagnosis of House Dust Mite Allergic Rhinitis

Objective: To evaluate the correlation between the routine diagnostic tests for house dust mite (HDM) sensitization in Chinese allergic rhinitis (AR) patients, including the skin prick test (SPT), serum HDM-specific immunoglobulin E (sIgE) and nasal smear eosinophilia. Methods: The ImmunoCAP assay was employed to detect serum total IgE and sIgE. The SPT and nasal smear eosinophil counts were performed using standard procedures. Results: Of 82 subjects with HDM-related symptoms and positive SPT results, 55 individuals showed an sIgE level equal to or greater than CAP class 1 for both Dermatophagoides pteronyssinus (Der p) and D. farinae (Der f), and 62 individuals demonstrated positive eosinophils in nasal smears. sIgE of Der p and Der f presented a linear correlation, and the level of serum HDM-sIgE was also positively correlated with total IgE. An increasing sIgE level was correlated with higher SPT grades in both Der p and Der f. Meanwhile, the correlation coefficient exhibited an increase in value with aging, and the 31- to 40-year age group demonstrated the highest value for both Der p and Der f. Conclusion: The positive correlation between SPT and sIgE reaction to HDM varied according to the age of patients with AR.

Maize pollen is an important allergen in occupationally exposed workers

BackgroundThe work- or environmental-related type I sensitization to maize pollen is hardly investigated. We sought to determine the prevalence of sensitization to maize pollen among exposed workers and to identify the eliciting allergens.MethodsIn July 2010, 8 out of 11 subjects were examined who were repeatedly exposed to maize pollen by pollinating maize during their work in a biological research department. All 8 filled in a questionnaire and underwent skin prick testing (SPT) and immune-specific analyses.Results5 out of the 8 exposed subjects had repeatedly suffered for at least several weeks from rhinitis, 4 from conjunctivitis, 4 from urticaria, and 2 from shortness of breath upon occupational exposure to maize pollen. All symptomatic workers had specific IgE antibodies against maize pollen (CAP class ≥ 1). Interestingly, 4 of the 5 maize pollen-allergic subjects, but none of the 3 asymptomatic exposed workers had IgE antibodies specific for grass pollen. All but one of the maize pollen-allergic subjects had suffered from allergic grass pollen-related symptoms for 6 to 11 years before job-related exposure to maize pollen. Lung function testing was normal in all cases. In immunoblot analyses, the allergenic components could be identified as Zea m 1 and Zea m 13. The reactivity is mostly caused by cross-reactivity to the homologous allergens in temperate grass pollen. Two sera responded to Zea m 3, but interestingly not to the corresponding timothy allergen indicating maize-specific IgE reactivity.ConclusionThe present data suggest that subjects pollinating maize are at high risk of developing an allergy to maize pollen as a so far underestimated source of occupational allergens. For the screening of patients with suspected maize pollen sensitization, the determination of IgE antibodies specific for maize pollen is suitable.

A new construction of caps

In this paper we present a general method to construct caps in higher-dimensional projective spaces. As an application, for q ≥ 8 even we obtain caps in PG(5,q) larger than the caps known so far, and a new class of caps of size ( q + 1 ) ( q 2 + 3 ) for q ≥ 7 odd.

A hierarchical spectral clustering and nonlinear dimensionality reduction scheme for detection of prostate cancer from magnetic resonance spectroscopy (MRS)

Magnetic resonance spectroscopy (MRS) has been shown to have great clinical potential as a supplement to magnetic resonance imaging in the detection of prostate cancer (CaP). MRS provides functional information in the form of changes in the relative concentration of specific metabolites including choline, creatine, and citrate which can be used to identify potential areas of CaP. With a view to assisting radiologists in interpretation and analysis of MRS data, some researchers have begun to develop computer-aided detection (CAD) schemes for CaP identification from spectroscopy. Most of these schemes have been centered on identifying and integrating the area under metabolite peaks which is then used to compute relative metabolite ratios. However, manual identification of metabolite peaks on the MR spectra, and especially via CAD, is a challenging problem due to low signal-to-noise ratio, baseline irregularity, peak overlap, and peak distortion. In this article the authors present a novel CAD scheme that integrates nonlinear dimensionality reduction (NLDR) with an unsupervised hierarchical clustering algorithm to automatically identify suspicious regions on the prostate using MRS and hence avoids the need to explicitly identify metabolite peaks. The methodology comprises two stages. In stage 1, a hierarchical spectral clustering algorithm is used to distinguish between extracapsular and prostatic spectra in order to localize the region of interest (ROI) corresponding to the prostate. Once the prostate ROI is localized, in stage 2, a NLDR scheme, in conjunction with a replicated clustering algorithm, is used to automatically discriminate between three classes of spectra (normal appearing, suspicious appearing, and indeterminate). The methodology was quantitatively and qualitatively evaluated on a total of 18 1.5 T in vivo prostate T2-weighted (w) and MRS studies obtained from the multisite, multi-institutional American College of Radiology (ACRIN) trial. In the absence of the precise ground truth for CaP extent on the MR imaging for most of the ACRIN studies, probabilistic quantitative metrics were defined based on partial knowledge on the quadrant location and size of the tumor. The scheme, when evaluated against this partial ground truth, was found to have a CaP detection sensitivity of 89.33% and specificity of 79.79%. The results obtained from randomized threefold and fivefold cross validation suggest that the NLDR based clustering scheme has a higher CaP detection accuracy compared to such commonly used MRS analysis schemes as z score and PCA. In addition, the scheme was found to be robust to changes in system parameters. For 6 of the 18 studies an expert radiologist laboriously labeled each of the individual spectra according to a five point scale, with 1/2 representing spectra that the expert considered normal and 3/4/5 being spectra the expert deemed suspicious. When evaluated on these expert annotated datasets, the CAD system yielded an average sensitivity (cluster corresponding to suspicious spectra being identified as the CaP class) and specificity of 81.39% and 64.71%, respectively.

Evaluating the Seasonality and Persistence of ETFs Performance and Volatility: Implications for Profitable Investing

By breaking down ETFs in broad, sector and international market categories as well as in large, medium and small cap classes of capitalization we demonstrate that a substantially positive November effect influences the performance of all ETF market categories and classes of capitalization. We also reveal the existence of a strong reverse December effect along with a modest reverse effect that affect the ETFs' volatility. The modest November effect in risk is accompanied by a strong reverse November effect in tracking error related to all ETF categories and classes. Moreover, we provide slight evidence for persistence in ETFs' November performance and strong evidence for persistence in ETFs' November risk and tracking error. Further research indicates that the investing strategies which respect the November patterns in ETFs' performance can beat the buy and hold strategies on an average and accumulated level during a five-year period and that investors can gain significant returns if they allow themselves to be exposed in greater level of volatility.