Supraglottoplasty for laryngomalacia with obstructive sleep apnea: A systematic review and meta-analysis

OBJECTIVES/HYPOTHESIS: To determine if apnea-hypopnea index (AHI) and lowest oxygen saturation (LSAT) improve following isolated supraglottoplasty for laryngomalacia with obstructive sleep apnea (OSA) in children. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Nine databases, including PubMed/MEDLINE, were searched through September 30, 2015. RESULTS: A total of 517 studies were screened; 57 were reviewed; and 13 met criteria. One hundred thirty-eight patients were included (age range: 1 month-12.6 years). Sixty-four patients had sleep exclusive laryngomalacia, and in these patients: 1) AHI decreased from a mean (M) ± standard deviation (SD) of 14.0 ± 16.5 (95% confidence interval [CI] 10.0, 18.0) to 3.3 ± 4.0 (95% CI 2.4, 4.4) events/hour (relative reduction: 76.4% [95% CI 53.6, 106.4]); 2) LSAT improved from a M ± SD of 84.8 ± 8.4% (95% CI 82.8, 86.8) to 87.6 ± 4.4% (95% CI 86.6, 88.8); 3) standardized mean differences (SMD) demonstrated a small effect for LSAT and a large effect for AHI; and 4) cure (AHI < 1 event/hour) was 10.5% (19 patients with individual data). Seventy-four patients had congenital laryngomalacia, and in these patients: 1) AHI decreased from a M ± SD of 20.4 ± 23.9 (95% CI 12.8, 28.0) to 4.0 ± 4.5 (95% CI 2.6, 5.4) events/hour (relative reduction: 80.4% [95% CI 46.6, 107.4]); 2) LSAT improved from a M ± SD of 74.5 ± 11.9% (95% CI 70.9, 78.1) to 88.4 ± 6.6% (95% CI 86.4, 90.4); 3) SMD demonstrated a large effect for both AHI and LSAT; and 4) cure was 26.5% (38 patients with individual data). CONCLUSION: Supraglottoplasty has improved AHI and LSAT in children with OSA and either sleep exclusive laryngomalacia or congenital laryngomalacia; however, the majority of them are not cured.

Efficacy of Preoperative Chemotherapy in Treatment of Children With Wilms’ Tumor: A Meta-Analysis

Context: To assess the efficacy of preoperative chemotherapy in Wilms’ tumor patients and explore its true value for specific subgroups. Objectives: In the presence of these controversies, a meta-analysis that examines the efficacy of preoperative chemotherapy in Wilms’ tumor patients and specific subgroups is needed to clarify these issues. The objective of this meta-analysis is to assess the efficacy of preoperative chemotherapy in Wilms’ tumor patients and explore its true value for specific subgroups. Data Sources: Computer-based systematic search with “preoperative chemotherapy”, “Neoadjuvant Therapy” and “Wilms’ tumor” as search terms till January 2013 was performed. Study Selection: No language restrictions were applied. Searches were limited to randomized clinical trials (RCTs) or retrospective studies in human participants under 18 years. A manual examination of references in selected articles was also performed. Data Extraction: Relative Risk (RR) and their 95% Confidence Interval (CI) for Tumor Shrinkage (TS), total Tumor Resection (TR), Event-Free Survival (EFS) and details of subgroup analysis were extracted. Meta-analysis was carried out with the help of the software STATA 11.0. Finally, four original Randomized Clinical Trials (RCTs) and 28 retrospective studies with 2375 patients were included. Results: For preoperative chemotherapy vs. up-front surgery (PC vs. SU) group, the pooled RR was 9.109 for TS (95% CI: 5.109 - 16.241; P < 0.001), 1.291 for TR (95% CI: 1.124 - 1.483; P < 0.001) and 1.101 for EFS (95% CI: 0.980 - 1.238; P = 0.106). For subgroup short course vs. long course (SC vs. LC), the pooled RR was 1.097 for TS (95% CI: 0.784 - 1.563; P = 0.587), 1.197 for TR (95% CI: 0.960 - 1.493; P = 0.110) and 1.006 for EFS (95% CI: 0.910 - 1.250; P = 0.430). Conclusions: Short course preoperative chemotherapy is as effective as long course and preoperative chemotherapy only benefits Wilms’ tumor patients in tumor shrinkage and resection but not event-free survival.

Investigating stratification, language diversity and mathematics classroom interaction

Research on the socio-political dimensions of language diversity in mathematics classrooms is under-theorised and largely focuses on language choice. These dimensions are, however, likely to influence mathematics classroom interaction in many other ways than participants’ choice of language. To investigate these influences, I propose that the notions ofheteroglossia, orders of indexicality and scale-jumping, can provide new theoretical tools with which to understand the links between classroom interaction and broader social patterns of marginalisation. To illustrate the utility of these ideas, I include some analysis of an episode observed in a sheltered elementary school second language mathematics classroom in Canada.

Analysis of Sampling Data

A Similar Exposure Group (SEG) can be created through the evaluation of workers performing the same or similar task, hazards they are exposed to, frequency and duration of their exposures, engineering controls available during their operations, personal protective equipment used, and exposure data. For this report, the samples of one facility that has collected nearly 40,000 various types of samples will be evaluated to determine if the creation of a SEG can be supported. The data will be reviewed for consistency with collection methods and laboratory detection limits. A subset of the samples may be selected based on the review. Data will also be statistically evaluated in order to determine whether the data is sufficient to terminate the sampling. IHDataAnalyst V1.27 will be used to assess the data. This program uses Bayesian Analysis to assist in making determinations. The 95 percent confidence interval will be calculated and evaluated in making decisions. This evaluation will be used to determine if a SEG can be created for any of the workers and determine the need for future sample collection. The data and evaluation presented in this report have been selected and evaluated specifically for the purposes of this project.

Zoroastrianism, Cosmology, and Chaos: A Detailed Analysis of the Musical Composition, Druj Aeterni

Druj Aeterni is a large chamber ensemble piece for flute, clarinet, French horn, two trumpets, piano, two percussionists, string quintet, and electric bass. My composition integrates three intellectual pursuits and interests, ancient mythology, cosmology, and mathematics. The title of the piece uses Latin and the language of the Avesta, the holy book of Zoroastrianism, and comments upon a philosophical perspective based in string theory. I abstract the cosmological implications of string theory, apply them to the terminology and theology of Zoroastrianism, and then structure the composition in consideration of a possible reconciliation. The analysis that follows incorporates analytical techniques similar to David Cope’s style of Vectoral Analysis.

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography

Purpose: The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). Methods: Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. Results: The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911–0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. Conclusions: Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

An in-depth characterisation of neonatal seizures by early continuous video-EEG analysis

Introduction Seizures are harmful to the neonatal brain; this compels many clinicians and researchers to persevere further in optimizing every aspects of managing neonatal seizures. Aims To delineate the seizure profile between non-cooled versus cooled neonates with hypoxic-ischaemic encephalopathy (HIE), in neonates with stroke, the response of seizure burden to phenobarbitone and to quantify the degree of electroclinical dissociation (ECD) of seizures. Methods The multichannel video-EEG was used in this research study as the gold standard to detect seizures, allowing accurate quantification of seizure burden to be ascertained in term neonates. The entire EEG recording for each neonate was independently reviewed by at least 1 experienced neurophysiologist. Data were expressed in medians and interquartile ranges. Linear mixed models results were presented as mean (95% confidence interval); p values <0.05 were deemed as significant. Results Seizure burden in cooled neonates was lower than in non-cooled neonates [60(39-224) vs 203(141-406) minutes; p=0.027]. Seizure burden was reduced in cooled neonates with moderate HIE [49(26-89) vs 162(97-262) minutes; p=0.020] when compared with severe HIE. In neonates with stroke, the background pattern showed suppression over the infarcted side and seizures demonstrated a characteristic pattern. Compared with 10 mg/kg, phenobarbitone doses at 20 mg/kg reduced seizure burden (p=0.004). Seizure burden was reduced within 1 hour of phenobarbitone administration [mean (95% confidence interval): -14(-20 to -8) minutes/hour; p<0.001], but seizures returned to pre-treatment levels within 4 hours (p=0.064). The ECD index in cooled, non-cooled neonates with HIE, stroke and in neonates with other diagnoses were 88%, 94%, 64% and 75% respectively. Conclusions Further research exploring the treatment effects on seizure burden in the neonatal brain is required. A change to our current treatment strategy is warranted as we continue to strive for more effective seizure control, anchored with use of the multichannel EEG as the surveillance tool.

Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants

Background: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings: We pooled 1479 studies that had measured the blood pressures of 19·1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127·0 mm Hg (95% credible interval 125·7–128·3) in men and 122·3 mm Hg (121·0–123·6) in women; age-standardised mean diastolic blood pressure was 78·7 mm Hg (77·9–79·5) for men and 76·7 mm Hg (75·9–77·6) for women. Global age-standardised prevalence of raised blood pressure was 24·1% (21·4–27·1) in men and 20·1% (17·8–22·5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1·13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants

Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence - defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs - in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. Findings: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4-7·0) in 1980 to 9·0% (7·2-11·1) in 2014 in men, and from 5·0% (2·9-7·9) to 7·9% (6·4-9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Interpretation Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.

What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis

Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.

Functional analysis of Arabidopsis thaliana lesion mimic mutant cfs1 in ESCRT complex-related protein trafficking

The Endosomal Sorting Complex Required for Transport (ESCRT)-complex is composed of four complexes, ESCRT-0-III. They sequentially act on a late endosome to sort mono-ubiquitinated transmembrane proteins into the intralumenal vesicle, forming of a multivesicular body(MVB) that is delivered to vacuole for degradation. In Arabidopsis thaliana, the loss of an ESCRT-I component, elch displays a cytokinesis defect; while a dominant negative expression of an ESCRT-III component results in cell death due to vacuolar loss. In this work, the function of a plant-specific ELCH-interactor, CELL DEATH RELATED FYVE/SYLF DOMAIN CONTAINING 1 (CFS1) and its influences on the ESCRT-complex function are investigated. CFS1 is a phosphatidylinositol-3-phosphate- and actin-binding protein. The cfs1 mutants mimic lesions in the first eldest leaf that propagate to the next eldest one. Genetic analyses have demonstrated that cell death in cfs1 does not require a functional ESCRT-I component; nevertheless, the loss of CFS1 alleviates elchcytokinesis defect, suggesting its influence on the ESCRT-I function. Further analyses reveal that cfs1 accumulates autophagosomes throughout its lifespan due to a decrease in autophagosome degradation, suggesting that as the plant ages, the cumulated autophagosomes falsely trigger effectors-triggered immunity that executes cell death in cfs1. As the ESCRT-complex has been demonstrated to be involved in the delivery of autophagosomes to vacuole and CFS1 homolog, CFS2 reportedly interacts with ATG8, it can be postulated from the results of this work that CFS1 alone or together with CFS2 function in sequestering mature autophagosomes onto MVBs. At the MVBs, the ESCRT-complex then mediates the fusion of autophagosome and MVB for subsequent delivery to vacuole.

Hilbert Space Valued Signal Plus Noise Models: Analysis of Structural Breaks under High Dimensionality and Temporal Dependence

This thesis is concerned with change point analysis for time series, i.e. with detection of structural breaks in time-ordered, random data. This long-standing research field regained popularity over the last few years and is still undergoing, as statistical analysis in general, a transformation to high-dimensional problems. We focus on the fundamental »change in the mean« problem and provide extensions of the classical non-parametric Darling-Erdős-type cumulative sum (CUSUM) testing and estimation theory within highdimensional Hilbert space settings. In the first part we contribute to (long run) principal component based testing methods for Hilbert space valued time series under a rather broad (abrupt, epidemic, gradual, multiple) change setting and under dependence. For the dependence structure we consider either traditional m-dependence assumptions or more recently developed m-approximability conditions which cover, e.g., MA, AR and ARCH models. We derive Gumbel and Brownian bridge type approximations of the distribution of the test statistic under the null hypothesis of no change and consistency conditions under the alternative. A new formulation of the test statistic using projections on subspaces allows us to simplify the standard proof techniques and to weaken common assumptions on the covariance structure. Furthermore, we propose to adjust the principal components by an implicit estimation of a (possible) change direction. This approach adds flexibility to projection based methods, weakens typical technical conditions and provides better consistency properties under the alternative. In the second part we contribute to estimation methods for common changes in the means of panels of Hilbert space valued time series. We analyze weighted CUSUM estimates within a recently proposed »high-dimensional low sample size (HDLSS)« framework, where the sample size is fixed but the number of panels increases. We derive sharp conditions on »pointwise asymptotic accuracy« or »uniform asymptotic accuracy« of those estimates in terms of the weighting function. Particularly, we prove that a covariance-based correction of Darling-Erdős-type CUSUM estimates is required to guarantee uniform asymptotic accuracy under moderate dependence conditions within panels and that these conditions are fulfilled, e.g., by any MA(1) time series. As a counterexample we show that for AR(1) time series, close to the non-stationary case, the dependence is too strong and uniform asymptotic accuracy cannot be ensured. Finally, we conduct simulations to demonstrate that our results are practically applicable and that our methodological suggestions are advantageous.

Analysis of Dyscalculia Evidences through Artificial Intelligence Systems

Dyscalculia is usually perceived of as a specific learning difficulty for mathematics or, more appropriately, arithmetic. Because definitions and diagnoses of dyscalculia are in their infancy and sometimes are contradictory. However, mathematical learning difficulties are certainly not in their infancy and are very prevalent and often devastating in their impact. Co-occurrence of learning disorders appears to be the rule rather than the exception. Co-occurrence is generally assumed to be a consequence of risk factors that are shared between disorders, for example, working memory. However, it should not be assumed that all dyslexics have problems with mathematics, although the percentage may be very high, or that all dyscalculics have problems with reading and writing. Because mathematics is very developmental, any insecurity or uncertainty in early topics will impact on later topics, hence to need to take intervention back to basics. However, it may be worked out in order to decrease its degree of severity. For example, disMAT, an app developed for android may help children to apply mathematical concepts, without much effort, that is turning in itself, a promising tool to dyscalculia treatment. Thus, this work will focus on the development of a Decision Support System to estimate children evidences of dyscalculia, based on data obtained on-the-fly with disMAT. The computational framework is built on top of a Logic Programming approach to Knowledge Representation and Reasoning, grounded on a Case-based approach to computing, that allows for the handling of incomplete, unknown, or even self-contradictory information.

Transition matrices characterizing a certain totally discontinuous map of the interval

We study a totally discontinuous interval map defined in [0,1] which is associated to a deformation of the shift map on two symbols 0−1. We define a sequence of transition matrices which characterizes the effect of the interval map on a family of partitions of the interval [0,1]. Recursive algorithms that build the sequence of matrices and their left and right eigenvectors are deduced. Moreover, we compute the Artin zeta function for the interval map.

Gwas analysis for the identification of molecular basis responsible for yield related traits and disease resistance in durum wheat

The PhD thesis was developed in the framework of Innovar H2020 project. This project aimed at using genomics, transcriptomics and phenotyping techniques to update varietal registration procedure used in Europe for Value of Cultivation and Use (VCU) and Distinctiness Uniformity and Stability (DUS) protocols. The phenotypic and genotypic diversity of a durum wheat panel were assessed for different agronomic traits, connected with wheat development, disease resistance and spike fertility. A panel of 253 durum wheat varieties was characterized for VCU and DUS traits and genotyped with Illumina 90K SNP Chip array (Wang et al., 2014). GWAS analysis was performed, detecting strong QTLs confirmed also by literature review. Candidate genes were identified for each trait and molecular markers will be developed to be used for marker assisted selection in breeding programs. As for disease resistance, the panel was evaluated for resistance to Soil-Borne-Cereal-Mosaic-Virus (SBCMV). A major QTL, sbm2, was detected on chromosome 2B responsible for durum wheat resistance (Maccaferri et al., 2011). The sbm2 interval was explored by fine mapping on segregant population using KASP markers and by RNASeq analysis, detecting candidate genes involved in plant-pathogen reaction. As regards yield related traits, detailed analysis was performed on the GNI-2A QTL (Milner et al., 2016), responsible for increased number spike fertility. Fine mapping analysis was performed on durum panel identifying hox2 a strong candidate gene, codifying for transcription factor protein. The gene is paralogue of GNI-1 (Sakuma et al., 2019), and it has a 4 kbp deletion responsible for increased number of florets per spikelet. To conclude, the herein reported thesis shows a complete characterization of agronomic and disease resistance traits in modern durum wheat varieties. The results obtained will augment available information for each variety, identifying informative molecular markers for breeding purposes and QTLs/candidate genes responsible for different agronomic traits.