Original Human Data Research Articles

Risk of Ocular Anomalies in Children Exposed In Utero to Antimalarials: A Systematic Literature Review.

To determine whether offspring from mothers with systemic lupus erythematosus (SLE), exposed in utero to antimalarials, have an increased risk of ocular anomalies during childhood versus unexposed SLE offspring. We systematically performed searches of PubMed, Embase, and Web of Science databases for original human data on fetal and/or child ocular outcomes following exposure to antimalarials during pregnancy and/or lactation, from their inception until March 2017. A total of 10 cohort studies and 2 randomized controlled trials, ranging in size from 6 to 444 exposed infants studied, and 3 case reports met the inclusion criteria for our systematic review. Collectively, 1,477 infants were studied, 789 of which were exposed to hydroxychloroquine or chloroquine. In all, 563 exposed infants had follow-up visits after delivery (ranging from <3 months to 19 years), and 331 of these exposed infants underwent ophthalmologic examinations during the follow-up period. Our review of the literature suggests a low-to-nonexistent risk of visual abnormalities in offspring exposed to antimalarials. In children exposed to appropriate doses of antimalarials antenatally, the risk of ocular toxicity appears low to nonexistent. The potential benefits and risks of antimalarials should be discussed in all SLE pregnancies, and high dosages should continue to be avoided.

Allergic rhinitis and asthma assessment of risk factors in pediatric patients: A systematic review

Allergic rhinitis (AR) is the most prevalent allergic disease in children and can be associated with asthma (A); this association can have significant effect on child's quality of life. The objective of this work was to systematically review existing literature on the risk factors of AR and A in children to better understand the link between these two diseases. We performed a literature search over the last 25 years in PubMed and Medline. Inclusion criteria comprised English language papers containing original human data with greater than 30 subjects and papers that statistically analyze the relationship between AR and A and the risk factor(s), in children population. A statistically significant correlation was found between children with AR and A and ambient Polycyclic Aromatic Hydrocarbons exposure, live in an industrialized city with elevated traffic, dampness and moulds exposure, electric cooking, male gender, single nucleotide polymorphisms in PTNP22 gene and CTLA-4 gene, fast food and margarine products consumption, use of paracetamol in last year, history of tuberculosis, parental atopy, high total serum IgE, antibiotics in uterus and infections in uterus exposure, history of formula feeding and caesarian section. A strong and complex link between AR and A was accounted: A represents a major risk factor for the onset of AR, that correlates with more severe asthmatic symptoms. Even the onset of A in a child with AR worsen it. The interaction of genetic and environmental risk factors and the consequent epigenetic, microbiota and immunological changes, were found to led to the development of AR and A in children, with both atopic and non-atopic pathways. Close monitoring of evidenced risk factors may help with an early recognize and treat A in patients with AR.

1685-P: Type 1 Diabetes Mellitus and Incident Bladder Cancer: A Systematic Review and Meta-analysis

Background: A credible body of epidemiologic evidence documents elevated bladder cancer risk among patients with type 2 diabetes, but risk among those with type 1 diabetes (T1DM) has received less attention. We sought to identify and quantitatively synthesize epidemiologic data on the association between T1DM and incident bladder cancer. Methods: We searched Medline, Embase, Cochrane, and Web of Science through June 5, 2018, to identify non-redundant English language reports of original human data estimating the association between T1DM and incident bladder cancer addressing age as potential confounder. Additional citations were identified through hand searching efforts including a Google Scholar search, contacting authors, and retrieving citations in selected studies. Candidate reports were critically appraised by two independent reviewers, with conflicts resolved by consensus. Harmonized estimates of the T1DM-bladder cancer association were extracted from qualifying reports and synthesized by random effects meta-analysis. Findings: Among 7,673 reports identified in the search, 59 warranted critical full text review, and 4 described 7 non-redundant studies satisfying inclusion criteria (N=362 T1DM patients). Estimate of the overall summary odds ratio association was 1.07 (95% CI: 0.87-1.32; I2: 69.1%, p heterogeneity= 0.001; 7 studies). Gender-specific summary estimates were 1.40 (95% CI: 0.95-2.05; I2: 73.9%, p heterogeneity= 0.002; 6 studies) for females, and 0.95 (95% CI: 0.71-1.26; I2: 61.4%, p heterogeneity= 0.024; 6 studies) for males. Interpretation: Available data reveal a modest positive association between incident bladder cancer and T1DM that does not achieve statistical significance. Etiologic interpretation is precluded by indicators of heterogeneity and design limitations of contributing studies, primarily confounding by smoking and error in measurement of diabetes in referent groups. Disclosure H.B. Oskoui: None. D.D. Bogumil: None. L. Kysh: None. M. Barrett: None. K. Siegmund: None. V.K. Cortessis: None.

Effects of environmental contaminants in inflammatory bowel disease: a systematic review

Introduction: The Inflammatory Bowel Disease (IBD) is characterized by a chronic inflammation of the gastrointestinal tract and it has two important forms: Crohn’s Disease and Ulcerative Colitis. Although the pathophysiology of the disease is mostly unknown, an interaction between the immune system, genetics, microbiome and environmental factors seems to be responsible for the disease onset. The role of environmental factors in the pathophysiology of this disease is reinforced if we consider the rapid growth in incidence and prevalence rates of IBD in areas where the incidence was previously low as, for example, Asia. However, the literature on the role of environmental factors in IBD is reduced and is not systematized. Hence, in this work a Systematic Review of the literature was performed. Materials and methods: For this systematic review the methodology “Navigation Guide Method for Grading Human Evidence” was used [1]. The research was carried out in three databases (Scopus, Web of Science, PubMed / MEDLINE). The inclusion criteria used were: research articles with original human data, clinically diagnosed inflammatory bowel disease, quantification of environmental contaminants and study of the association between environmental contaminants and inflammatory bowel disease. Only articles written in Portuguese, English, French or Spanish were included. Results: Sixteen studies were included in this systematic review. Of these, 13 studied Inflammatory Bowel Disease in general, 2 studies included only patients with Crohn’s Disease and 1 study included only patients with Ulcerative Colitis. The most studied environmental contaminants were sulfur dioxide, nitrogen dioxide, carbon monoxide, particulate matter (PM), perfluorooctanoic acid, aluminum, iron, zinc, copper, titanium dioxide, silicates and endotoxins. We also identified different categories of studies, 4 studies on the effects of air pollution, 3 on the intake of contaminated water and 3 on the effects of diet. Additionally, 2 studies evaluated the serum concentrations of contaminants, 1 studied the impact of exposure to house dust, 2 attempted a cell characterization of IBD patients and in another colitis was induced. Overall, the quality of evidence was rated “moderate to low” and the strength of evidence as “Inadequate evidence on toxicity”. Discussion and conclusions: In this systematic review, we have identified different classes of environmental contaminants associated with IBD, but studies reporting their concentration in biological matrices are rare. Based on a moderate to low level of quality, the available evidence gathered in this Systematic Review is insufficient to access the role of environmental contaminants in inflammatory bowel disease. New epidemiological studies are necessary.

A Stochastic and Mathematically Integrative Model of the Gender Modulation of Cardiorespiratory Activity.

Breath-to-breath interval (BBI) and heartbeat-toheartbeat interval (RRI) variability intrinsically contain a combination of random and temporally scaled characteristics. The objective of this study was to design and test a stochastic and mathematically integrative model (SIM) of cardiorespiratory function that could replicate any genderbased differences in breathing or heartrate variability during a calm, resting state. BBI and RRI sequences were recorded from 12 healthy subjects. Inter-breath and inter-beat memory were estimated with an autocorrelation function, and discrete probability density functions were created by fitting polynomial curves to the normalized histograms of each sequence. The SIM generated an artificial BBI or RRI sequence by constructing a random series of interval values selected from a discrete PDF, and then integrating the series with parameters from the autocorrelation analysis. Fractal scaling was quantified with detrended fluctuation analysis. A significant gender difference was identified in the autocorrelation coefficients of the BBI. The SIM produced artificial BBI and RRI sequences with significant fractal scaling as compared to randomly-shuffled surrogate data (p < 0.001), and with fractal-scaling characteristics similar to the original human data. The SIMgenerated BBI sequences also exhibited the same significant gender-based differences as identified in the human data (p < 0.01). In conclusion, this research demonstrated a stochastic and integrative model that replicated the gender-based differences in fractal scaling in resting human breathing patterns.

List of Societies

Allergic rhinitis (AR) is the most prevalent allergic disease in children and can be associated with asthma (A); this association can have significant effect on child's quality of life. The objective of this work was to systematically review existing literature on the risk factors of AR and A in children to better understand the link between these two diseases. We performed a literature search over the last 25 years in PubMed and Medline. Inclusion criteria comprised English language papers containing original human data with greater than 30 subjects and papers that statistically analyze the relationship between AR and A and the risk factor(s), in children population. A statistically significant correlation was found between children with AR and A and ambient Polycyclic Aromatic Hydrocarbons exposure, live in an industrialized city with elevated traffic, dampness and moulds exposure, electric cooking, male gender, single nucleotide polymorphisms in PTNP22 gene and CTLA-4 gene, fast food and margarine products consumption, use of paracetamol in last year, history of tuberculosis, parental atopy, high total serum IgE, antibiotics in uterus and infections in uterus exposure, history of formula feeding and caesarian section. A strong and complex link between AR and A was accounted: A represents a major risk factor for the onset of AR, that correlates with more severe asthmatic symptoms. Even the onset of A in a child with AR worsen it. The interaction of genetic and environmental risk factors and the consequent epigenetic, microbiota and immunological changes, were found to led to the development of AR and A in children, with both atopic and non-atopic pathways. Close monitoring of evidenced risk factors may help with an early recognize and treat A in patients with AR.

A stochastic and mathematically integrative model of the control of human heart rate.

The innate variability of the heart rate contains both random and temporally scaled components. The objective of this study was to design a stochastic and mathematically integrative model (SIM) of the control of human heart rate that could replicate the cardiac rhythm during rest and two distinct states of exercise. Heartbeat-to-heartbeat interval (RRI) were recorded from 8 healthy subjects during rest and two exercise levels. Signal memory in RRI sequences was estimated with autocorrelation, and probability density functions (PDFs) were created by fitting polynomial curves to the normalized histograms of the RRI sequences. The SIM generated fictive RRI sequences by randomly selecting RRI values from a PDF and integrating the series using parameters derived from the autocorrelation analysis. Fractal-scaling in the model RRI sequences was quantified with detrended fluctuation analysis. After optimizing the model with the autocorrelation-based and PDF parameters, the SIM was able to produce fictive RRI sequences with significant fractal scaling (statistically assessed with surrogate analysis, p <; 0.001), and with fractal-scaling characteristics similar to the original human data (p = 0.62). Increasing the length of the SIM-generated sequences did not alter the temporal scaling of the model sequences. In conclusion, this research demonstrated a stochastic and integrative model that can replicate the temporally correlated characteristics of the human heart rate.

The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis

Although it is well established that heavy alcohol consumption increases the risk of hypertension, little is known about the effect of a reduction of alcohol intake on blood pressure. We aimed to assess the effect of a reduction in alcohol consumption on change in blood pressure stratified by initial amount of alcohol consumption and sex in adults. In this systematic review and meta-analysis, we searched MedLine, Embase, CENTRAL, and ClinicalTrials.gov from database inception up to July 13, 2016, for trials investigating the effect of a change of alcohol consumption on blood pressure in adults using keywords and MeSH terms related to alcohol consumption, blood pressure, and clinical trials, with no language restrictions. We also searched reference lists of identified articles and published meta-analyses and reviews. We included full-text articles with original human trial data for the effect of a change of alcohol consumption on blood pressure in adults, which reported a quantifiable change in average alcohol consumption that lasted at least 7 days and a corresponding change in blood pressure. We extracted data from published reports. We did random-effects meta-analyses stratified by amount of alcohol intake at baseline. All meta-analyses were done with Stata (version 14.1). For the UK, we modelled the effect of a reduction of alcohol consumption for 50% of the population drinking more than two standard drinks per day (ie, 12 g pure alcohol per drink). 36 trials with 2865 participants (2464 men and 401 women) were included. In people who drank two or fewer drinks per day, a reduction in alcohol was not associated with a significant reduction in blood pressure; however, in people who drank more than two drinks per day, a reduction in alcohol intake was associated with increased blood pressure reduction. Reduction in systolic blood pressure (mean difference -5·50 mm Hg, 95% CI -6·70 to -4·30) and diastolic blood pressure (-3·97, -4·70 to -3·25) was strongest in participants who drank six or more drinks per day if they reduced their intake by about 50%. For the UK, the results would translate into more than 7000 inpatient hospitalisations and 678 cardiovascular deaths prevented every year. Reducing alcohol intake lowers blood pressure in a dose-dependent manner with an apparent threshold effect. Implementation of effective alcohol interventions in people who drink more than two drinks per day would reduce the disease burden from both alcohol consumption and hypertension, and should be prioritised in countries with substantial alcohol-attributable risk. National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health (NIH).

Longitudinal Cardiovascular Outcomes of Sleep Disordered Breathing in Children: A Meta-Analysis and Systematic Review.

The presence of sleep disordered breathing (SDB) is known to impact long-term cardiovascular morbidity in adults; however, the long-term effects in children are poorly understood. We aimed to systematically review and synthesize studies published to date on the long-term effects of SDB in children. Meta-analysis and systematic review using PubMed, CINAHL, Embase, and Scopus (all indexed years). We searched for English-language articles containing original human data from prospective studies, with ≥7 participants, in children ≤18 years of age. Data regarding study design, demographics, clinical characteristics, outcomes, level of evidence, and risk of bias were obtained. Articles were independently reviewed by three investigators. Retrospective and cross-sectional studies were excluded. Of 1701 identified abstracts, 25 articles (combined n = 1418) were ultimately included. All studies reported longitudinal outcomes following treatment of SDB, 21 studies exclusively reporting outcomes after adenotonsillectomy. Therefore, studies were combined to objectively assess the effect of SDB treatment on cardiovascular outcomes. Although all cardiovascular parameters were within the normal range at baseline, at follow-up there was a significant decrease in mean pulmonary artery pressure, right ventricular end diastolic diameter, heart rate, mitral Em/Am ratio, and C-reactive protein. There was no significant change in interventricular septum thickness, left ventricular parameters (shortening fraction, systolic and end diastolic diameters, ejection fraction, posterior wall thickness, isovolumetric relaxation time), left atrial diameter, and aortic and pulmonary valve peak velocities. Studies assessing the long-term cardiovascular effects of SDB in children are limited. The available literature indicates effects on autonomic function, right, and left heart function following treatment for SDB. However, well-designed, large-scale, prospective cohort studies (using standardized outcomes) are needed to better understand the relationship of cardiovascular morbidity in the context of pediatric SDB.

Primary immunodeficiency and recalcitrant chronic sinusitis: a systematic review.

A subset of patients with chronic rhinosinusitis (CRS) has disease refractory to standard therapies. Primary immunodeficiency should be considered in this group. Past literature has demonstrated an association between immunodeficiency and chronic sinusitis. A systematic literature search was performed using OVID, MEDLINE, EMBASE, and Cochrane databases to identify English language papers containing original human data on subjects with primary immunodeficiency and chronic sinusitis. A total of 39 studies met inclusion criteria. Data was collected pertaining to immune dysfunction in patients with chronic sinusitis, the clinical workup for these patients, and the effectiveness of medical and surgical treatments. The studies were assessed to determine their level of evidence. The majority of studies were supported by Level 4 evidence. Up to 50% of patients with recalcitrant CRS were found to have immune dysfunction. The most frequent primary immunodeficiencies studied were common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA). Common collected data included measurement of serum immunoglobulins and functional antibody responses. Treatments reviewed include immunoglobulin replacement, long-term antibiotics and endoscopic sinus surgery. Patients with recalcitrant CRS should be evaluated for primary immunodeficiency. This should include as assessment of quantitative serum immunoglobulin levels as well as functional antibody responses. Medical therapy, particularly immunoglobulin replacement therapy, appears to be most effective when administered at high doses early in the disease course. The addition of surgery is less clearly supported, but may also provide benefit if performed early.

The effects of anesthesia and opioids on the upper airway: A systematic review.

Drug-induced sleep endoscopy (DISE) is used to determine surgical therapy for obstructive sleep apnea (OSA); however, the effects of anesthesia on the upper airway are poorly understood. Our aim was to systematically review existing literature on the effects of anesthetic agents on the upper airway. PubMed, CINAHL, EBM reviews and Scopus (all indexed years). Inclusion criteria included English language articles containing original human data. Two investigators independently reviewed all articles for outcomes related to upper airway morphology, dynamics, neuromuscular response, and respiratory control. The initial search yielded 180 abstracts; 56 articles were ultimately included (total population = 8,540). The anesthetic agents studied were: topical lidocaine, propofol, dexmedetomidine, midazolam, pentobarbital, sevoflurane, desflurane, ketamine, and opioids. Outcome measures were diverse and included imaging studies, genioglossus electromyography, endoscopic airway assessment, polysomnography, upper airway closing pressure, and clinical evidence of obstruction. All agents caused some degrees of airway collapse. Dexmedetomidine did not have dose-dependent effects when evaluated using cine magnetic resonance imaging, unlike sevoflurane, isoflurane, and propofol, and caused less dynamic collapse than propofol. Studies assessing the effect of anesthesia on the upper airway in patients with and without OSA are limited, and few compare effects between agents. Medications with minimal effect on respiratory control (e.g., dexmedetomidine) may work best for DISE.

Systematic review of site of obstruction identification and non-CPAP treatment options for children with persistent pediatric obstructive sleep apnea.

Although adenotonsillectomy is accepted as a first-line therapy for pediatric obstructive sleep apnea (OSA), there is currently no consensus regarding optimal methods for identifying the sites of obstruction or treatment of children with persistent disease after surgery. With this in mind, our aim was to systematically review the English-language literature pertaining to these issues. Systematic review. We searched all indexed years of Pubmed, Cochrane CENTRAL, DynaMed, UpToDate, CINAHL, and Scopus for English-language articles containing original human data, with ≥ 7 participants, all < 18 years old. Data regarding study design, demographics, clinical characteristics/outcomes, level of evidence, and risk of bias were obtained. Articles were independently reviewed by two investigators. Of 758 identified abstracts, 24 articles (combined population = 960) were ultimately included. Seventeen (71%) described methods to identify site(s) of obstruction: drug-induced sleep endoscopy (11/24), cine magnetic resonance imaging (MRI) (3/24), and alternative imaging (3/24). Treatment options included lingual tonsillectomy (n = 6), with success rates of 57% to 88% (Cohen's effect size d = 1.38), as well as supraglottoplasty (n = 4), with success rates of 58% to 72% (d = 0.64). Additional treatments included medications and surgery (e.g., partial midline glossectomy and tongue suspension). Drug-induced sleep endoscopy and cine MRI are the most commonly reported tools to identify sites of obstruction for children with persistent OSA; however, these techniques have not yet been clearly linked to outcomes. Evidence for treatment is extremely limited and focuses primarily on lingual tonsillectomy and supraglottoplasty. Also, reports regarding appropriate patient selection and outcomes in obese or otherwise healthy children are scant.

Qualitative synthesis and systematic review of otolaryngology in undergraduate medical education.

Although 25% of primary care complaints are otolaryngology related, otolaryngology instruction is not required in most medical schools. Our aim was to systematically review existing literature on the inclusion of otolaryngology in undergraduate medical education. PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Education Resources Information Center. Our search encompassed all indexed years through December 29, 2014. Inclusion criteria were English language, original human data, and a focus on medical student education. Data regarding study design, teacher, educational topic, educational methods, and setting were extracted from each article. Two investigators independently reviewed all articles. Our initial search yielded 436 articles; 87 underwent full-text evaluation and 47 remained in the final review. The majority of studies were conducted in the United States (40%), United Kingdom (23%), and Canada (17%) and represented a single institutional experience. Studies were classified as needs assessments (36%), curriculum descriptions (15%), educational methods (36%), and skills assessments (32%); 81% were levels of evidence 3 or 4. Most reports indicated that otolaryngology rotations are not compulsory. Studies indicated the need for increased exposure to otolaryngology. Educational methods such as team-based learning, simulation, online learning, and clinical skills assessments may offer ways to increase exposure without overburdening clinical faculty and require further study. Data suggest that a universal otolaryngology medical student curriculum would be valuable and aid in resource sharing across institutions. We recommend that an assessment be performed to determine topics and skills that should comprise this curriculum. NA.

The association between secondhand smoke and sleep-disordered breathing in children: a systematic review.

To systematically review existing literature on the association between secondhand smoke and sleep-disordered breathing in children. PubMed, Embase, Cochrane CENTRAL, Web of Science, and Scopus. Inclusion criteria included English-language papers containing original human data, with seven or more subjects and age <18 years. Data were systematically collected on study design, patient demographics, clinical characteristics/outcomes, and level of evidence. Two investigators independently reviewed all manuscripts. The initial search yielded 72 abstracts; 18 articles were ultimately included with a total study population of 47,462 patients. Fifteen (83%) articles found a statistically significant association between secondhand smoke and sleep-disordered breathing. All were case-control studies. Quality of articles based on the Newcastle-Ottawa scale averaged 5.8/9 stars. Secondhand smoke was characterized by serum cotinine testing in only two (11%) studies. Sleep-disordered breathing was quantified by polysomnography in only four (22%) of the studies and only one (6%) classified subject using polysomnography exclusively. Habitual snoring was the most common form of sleep-disordered breathing studied in 14/18 (78%) studies, whereas obstructive sleep apnea was reported in one (6%) study and sleep-related hypoxia in another (6%) study. Although the majority of studies included in this review found a significant association between secondhand smoke and sleep-disordered breathing, all of them were evidence level 3b, for an overall grade of B (Oxford Centre for Evidence-based Medicine). Further higher-quality studies should be performed in the future to better evaluate the relationship between second- smoke and sleep-disordered breathing in children.

The role of secondhand smoke in allergic rhinitis: a systematic review

The objective of this work was to systematically review existing literature on the association between allergic rhinitis (AR) and secondhand smoking (SHS) in children and adults. We performed a literature search encompassing the last 25 years in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane CENTRAL, Web of Science, Scopus, and EMBASE. Inclusion criteria included English language papers containing original human data with greater than 6 subjects. Data was systematically collected on study design, patient demographics, clinical characteristics/outcomes, and level-of-evidence (Oxford Center of Evidence-Based Medicine). Quality assessment of the studies was performed using the Newcastle-Ottawa scale. Two investigators independently reviewed all manuscripts. The initial search yielded 590 abstracts, of which 40 articles were included. 12 (37.5%) of the 32 articles studying children and 5 (62.5%) of the 8 articles studying adults showed a statistically significant association between AR and SHS. One article was a prospective cohort study (Level 2b) and all other articles were case-control studies (Level 3b). For characterizing AR, 10 (25%) studies included skin-prick testing and 5 (12.5%) used in vitro testing. For determining presence of SHS, 39 (97.5%) of the studies used questionnaires and 1 article used a cotinine/creatinine ratio. This review demonstrated a majority of adult studies vs a minority of children studies found a significant association between AR and SHS. However, the percent difference between age groups was not statistically significant. Further higher-quality studies with validated methods for diagnosing AR and quantifying SHS exposure should be performed to better evaluate the relationship between AR and SHS in adults and children.

The role of secondhand smoke in sinusitis: a systematic review

The objective of this study was to systematically review existing literature on the association between sinusitis and secondhand smoke (SHS) exposure. We performed a literature search encompassing the last 25 years in PubMed, EMBASE, and Cochrane CENTRAL. Inclusion criteria included English language papers containing original human data with at least 7 subjects. Data was systematically collected on study design, patient demographics, clinical characteristics/outcomes, and level-of-evidence (Oxford Center for Evidence-Based Medicine). Quality assessment was performed using the Newcastle-Ottawa scale. Two investigators independently reviewed all manuscripts. The initial search yielded 116 abstracts, of which 19 articles were included. Thirteen (68.4%) of the 19 articles showed a statistically significant association between sinusitis and SHS. Seven (36.8%) studies specifically evaluated chronic rhinosinusitis (CRS) with 5 (71.4%) CRS studies demonstrating a significant association between CRS and SHS. Seventeen articles were case-control studies (Level 3b). For characterizing sinusitis, 6 (31.6%) studies included computed tomography (CT) or endoscopy in the diagnostic criteria, with 5 of these studies following rhinosinusitis taskforce guidelines. For determining presence of SHS, all studies used questionnaires and 2 (10.5%) studies also reported serum or urine cotinine levels. A majority of the studies (68.4%) included in this systematic review showed a significant association between sinusitis and SHS. Furthermore, 5 (83.3%) of the 6 studies with objective diagnostic criteria (CT, endoscopy) found a significant association between sinusitis and SHS. Further higher-quality studies with objective diagnosis of sinusitis and quantification of SHS exposure should be performed in the future to better evaluate the relationship between sinusitis and SHS.

Generation of a suite of 3D computer‐generated breast phantoms from a limited set of human subject data

The authors previously reported on a three-dimensional computer-generated breast phantom, based on empirical human image data, including a realistic finite-element based compression model that was capable of simulating multimodality imaging data. The computerized breast phantoms are a hybrid of two phantom generation techniques, combining empirical breast CT (bCT) data with flexible computer graphics techniques. However, to date, these phantoms have been based on single human subjects. In this paper, the authors report on a new method to generate multiple phantoms, simulating additional subjects from the limited set of original dedicated breast CT data. The authors developed an image morphing technique to construct new phantoms by gradually transitioning between two human subject datasets, with the potential to generate hundreds of additional pseudoindependent phantoms from the limited bCT cases. The authors conducted a preliminary subjective assessment with a limited number of observers (n = 4) to illustrate how realistic the simulated images generated with the pseudoindependent phantoms appeared. Several mesh-based geometric transformations were developed to generate distorted breast datasets from the original human subject data. Segmented bCT data from two different human subjects were used as the "base" and "target" for morphing. Several combinations of transformations were applied to morph between the "base' and "target" datasets such as changing the breast shape, rotating the glandular data, and changing the distribution of the glandular tissue. Following the morphing, regions of skin and fat were assigned to the morphed dataset in order to appropriately assign mechanical properties during the compression simulation. The resulting morphed breast was compressed using a finite element algorithm and simulated mammograms were generated using techniques described previously. Sixty-two simulated mammograms, generated from morphing three human subject datasets, were used in a preliminary observer evaluation where four board certified breast radiologists with varying amounts of experience ranked the level of realism (from 1 = "fake" to 10 = "real") of the simulated images. The morphing technique was able to successfully generate new and unique morphed datasets from the original human subject data. The radiologists evaluated the realism of simulated mammograms generated from the morphed and unmorphed human subject datasets and scored the realism with an average ranking of 5.87 ± 1.99, confirming that overall the phantom image datasets appeared more "real" than "fake." Moreover, there was not a significant difference (p > 0.1) between the realism of the unmorphed datasets (6.0 ± 1.95) compared to the morphed datasets (5.86 ± 1.99). Three of the four observers had overall average rankings of 6.89 ± 0.89, 6.9 ± 1.24, 6.76 ± 1.22, whereas the fourth observer ranked them noticeably lower at 2.94 ± 0.7. This work presents a technique that can be used to generate a suite of realistic computerized breast phantoms from a limited number of human subjects. This suite of flexible breast phantoms can be used for multimodality imaging research to provide a known truth while concurrently producing realistic simulated imaging data.

The association between allergic rhinitis and sleep‐disordered breathing in children: a systematic review

The objective of this work was to systematically review existing literature on the association between allergic rhinitis (AR) and sleep-disordered breathing (SDB) in children. We performed a literature search encompassing the last 25 years in PubMed, EMBASE, and Cochrane CENTRAL. Inclusion criteria included English-language papers containing original human data, number of subjects ≥7, and age <18 years old. Data was systematically collected on study design, patient demographics, clinical characteristics/outcomes, and level-of-evidence. Two investigators independently reviewed all articles. The initial search yielded 433 abstracts, of which 18 articles were included. Twelve (67%) of the 18 articles showed a statistically significant association between AR and SDB. All articles were either case-series or case-control studies. Based on the Newcastle-Ottawa scale, the quality of the articles was determined to be fair to good. For characterizing AR, 7 (39%) studies included skin-prick testing and/or in vitro testing. For determining presence of SDB, 7 (39%) of the studies used polysomnographic data, of which 1 study incorporated data from a home polysomnogram. Habitual snoring was the most common form of SDB studied, in 10 (56%) of the articles. Obstructive sleep apnea was studied in 6 (33%) articles. Although the majority of the studies included in this review showed a significant association between AR and SDB, all of the studies were evidence level 3b and 4, for an overall grade of B- evidence (Oxford Evidence-Based Medicine Center). Further higher-quality studies should be performed in the future to better evaluate the relationship between AR and SDB in children.

Predicting human action with human and non-human movement kinematics: behavioural and fMRI findings

Human observers perceive movement with typical human kinematics more sensitively than movement with non-human kinematics, even when its velocity profile is more uniform. In a behavioural experiment and a subsequent fMRI study, we tested the influence of movement kinematics on the accuracy of predicting the time course of another individual’s actions. A temporal occlusion paradigm was used in which participants observed short video sequences that were briefly occluded. The videos either showed a human point-light shape that was animated with human movement (natural condition) or with artificial movement (artificial condition). For generating the artificial movement, original human motion-capture data were manipulated to obtain movement that was more uniform regarding velocity profiles and trajectories. During brief occlusions, the participants predicted the actions and judged after occlusion whether the actions were continued coherently in time or shifted to an earlier or later frame. The results revealed higher error rates in the artificial compared to the natural condition, suggesting a perceptual advantage for movement with a human velocity profile. This corresponds to the notion of a close interaction between observed and executed movement. This notion was challenged in an fMRI experiment which employed the same stimuli in a prediction and in an observation condition. The observation condition required answering questions about movement details. Prediction in contrast to observation induced right premotor activation whereas observation strongly activated the left premotor cortex. The results suggest that the involvement of the motor system was modulated by task instructions. Interestingly, activation in several cortical areas, including the visual system, was modulated by the increasing divergence from human movement characteristics. An interpretation in the framework of the simulation account of action perception and its limitations will be discussed.

Marx e Lukács e o problema da individualidade: algumas aproximações

A última grande obra filosófica de Gyorgy Lukács, para uma ontologia do ser social, assim como os prolegômenos constituem no interior do marxismo uma inovação radical diante da interpretação dispensada à obra de Marx ao longo do último século, pois têm o mérito de enfatizar o caráter ontológico do pensamento de Marx. Entretanto, se deve sublinhar que, segun- do o filósofo húngaro, a categoria da generidade explicita a concepção revolucionária sobre o ser e o devir do gênero huma- no instaurada por Marx. Lukács identifica o lócus genético dessa concepção, ou seja, a superação do gênero natural mudo e o surgimento do gênero propriamente humano, precisamente na práxis que constitui a maneira segundo a qual a “adaptação ativa” se desenvolve e na qual, por consequência, se realiza de modo contraditório e não idêntico a constituição processual do ser social. Nesse contexto, Lukács não compreende a individua-lidade como um dado humano originário, mas, antes, como categoria que se constitui também historicamente, sobre o fundamento de uma “determinação recíproca” com a generidade.