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1.
Mol Genet Genomic Med ; : e928, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478359

RESUMO

BACKGROUND: ENAM mutations cause autosomal dominant or recessive amelogenesis imperfecta (AI) and show a dose effect: enamel malformations are more severe or only penetrant when both ENAM alleles are defective. METHODS: Whole exome sequences of recruited AI probands were initially screened for mutations in known AI candidate genes. Sanger sequencing was used to confirm sequence variations and their segregation with the disease phenotype. The co-occurrence of ENAM and LAMA3 mutations in one family raised the possibility of digenic inheritance. Enamel formed in Enam+/+ Ambn+/+ , Enam+/- , Ambn+/- , and Enam+/- Ambn+/- mice was characterized by dissection and backscattered scanning electron microscopy (bSEM). RESULTS: ENAM mutations segregating with AI in five families were identified. Two novel ENAM frameshift mutations were identified. A single-nucleotide duplication (c.395dupA/p.Pro133Alafs*13) replaced amino acids 133-1142 with a 12 amino acid (ATTKAAFEAAIT*) sequence, and a single-nucleotide deletion (c.2763delT/p.Asp921Glufs*32) replaced amino acids 921-1142 with 31 amino acids (ESSPQQASYQAKETAQRRGKAKTLLEMMCPR*). Three families were heterozygous for a previously reported single-nucleotide ENAM deletion (c.588+1delG/p.Asn197Ilefs*81). One of these families also harbored a heterozygous LAMA3 mutation (c.1559G>A/p.Cys520Tyr) that cosegregated with both the AI phenotype and the ENAM mutation. In mice, Ambn+/- maxillary incisors were normal. Ambn+/- molars were also normal, except for minor surface roughness. Ambn+/- mandibular incisors were sometimes chalky and showed minor chipping. Enam+/- incisor enamel was thinner than normal with ectopic mineral deposited laterally. Enam+/- molars were sometimes chalky and rough surfaced. Enam+/- Ambn+/- enamel was thin and rough, in part due to ectopic mineralization, but also underwent accelerated attrition. CONCLUSION: Novel ENAM mutations causing AI were identified, raising to 22 the number of ENAM variations known to cause AI. The severity of the enamel phenotype in Enam+/- Ambn+/- double heterozygous mice is caused by composite digenic effects. Digenic inheritance should be explored as a cause of AI in humans.

2.
Rev Sci Instrum ; 90(8): 083702, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472628

RESUMO

This article describes a home-built scanning electrochemical microscope capable of achieving high areal imaging rates through the use of continuous line probes (CLPs) and compressed sensing (CS) image reconstruction. The CLP is a nonlocal probe consisting of a band electrode, where the achievable spatial resolution is set by the thickness of the band and the achievable imaging rate is largely determined by its width. A combination of linear and rotational motors allows for CLP scanning at different angles over areas up to 25 cm2 to generate the raw signal necessary to reconstruct the desired electrochemical image using CS signal analysis algorithms. Herein, we provide detailed descriptions of CLP fabrication, microscope design, and the procedures used to carry out scanning electrochemical microscopy imaging with CLPs. In order to illustrate the basic operating procedures for the microscope, line scans and images measured in the substrate generation-probe-collection mode for flat samples containing platinum disk electrodes are presented. These exemplary measurements illustrate methods for calibrating the positioning system, positioning and cleaning the CLP, and verifying proper positioning/probe sensitivity along its length.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31494544

RESUMO

Blind deconvolution is the problem of recovering a convolutional kernel a0 and an activation signal x0 from their convolution . This problem is ill-posed without further constraints or priors. This paper studies the situation where the nonzero entries in the activation signal are sparsely and randomly populated. We normalize the convolution kernel to have unit Frobenius norm and cast the sparse blind deconvolution problem as a nonconvex optimization problem over the sphere. With this spherical constraint, every spurious local minimum turns out to be close to some signed shift truncation of the ground truth, under certain hypotheses. This benign property motivates an effective two stage algorithm that recovers the ground truth from the partial information offered by a suboptimal local minimum. This geometry-inspired algorithm recovers the ground truth for certain microscopy problems, also exhibits promising performance in the more challenging image deblurring problem. Our insights into the global geometry and the two stage algorithm extend to the convolutional dictionary learning problem, where a superposition of multiple convolution signals is observed.

4.
J Am Coll Cardiol ; 74(10): 1317-1328, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31488269

RESUMO

BACKGROUND: Growing evidence exists about the fetal and environmental origins of hypertension, but mainly limited to single-exposure studies. The exposome has been proposed as a more holistic approach by studying many exposures simultaneously. OBJECTIVES: This study aims to evaluate the association between a wide range of prenatal and postnatal exposures and blood pressure (BP) in children. METHODS: Systolic and diastolic BP were measured among 1,277 children from the European HELIX (Human Early-Life Exposome) cohort aged 6 to 11 years. Prenatal (n = 89) and postnatal (n = 128) exposures include air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals, and lifestyles. Two methods adjusted for confounders were applied: an exposome-wide association study considering the exposures independently, and the deletion-substitution-addition algorithm considering all the exposures simultaneously. RESULTS: Decreases in systolic BP were observed with facility density (ß change for an interquartile-range increase in exposure: -1.7 mm Hg [95% confidence interval (CI): -2.5 to -0.8 mm Hg]), maternal concentrations of polychlorinated biphenyl 118 (-1.4 mm Hg [95% CI: -2.6 to -0.2 mm Hg]) and child concentrations of dichlorodiphenyldichloroethylene (DDE: -1.6 mm Hg [95% CI: -2.4 to -0.7 mm Hg]), hexachlorobenzene (-1.5 mm Hg [95% CI: -2.4 to -0.6 mm Hg]), and mono-benzyl phthalate (-0.7 mm Hg [95% CI: -1.3 to -0.1 mm Hg]), whereas increases in systolic BP were observed with outdoor temperature during pregnancy (1.6 mm Hg [95% CI: 0.2 to 2.9 mm Hg]), high fish intake during pregnancy (2.0 mm Hg [95% CI: 0.4 to 3.5 mm Hg]), maternal cotinine concentrations (1.2 mm Hg [95% CI: -0.3 to 2.8 mm Hg]), and child perfluorooctanoate concentrations (0.9 mm Hg [95% CI: 0.1 to 1.6 mm Hg]). Decreases in diastolic BP were observed with outdoor temperature at examination (-1.4 mm Hg [95% CI: -2.3 to -0.5 mm Hg]) and child DDE concentrations (-1.1 mm Hg [95% CI: -1.9 to -0.3 mm Hg]), whereas increases in diastolic BP were observed with maternal bisphenol-A concentrations (0.7 mm Hg [95% CI: 0.1 to 1.4 mm Hg]), high fish intake during pregnancy (1.2 mm Hg [95% CI: -0.2 to 2.7 mm Hg]), and child copper concentrations (0.9 mm Hg [95% CI: 0.3 to 1.6 mm Hg]). CONCLUSIONS: This study suggests that early-life exposure to several chemicals, as well as built environment and meteorological factors, may affect BP in children.

6.
Arch Dis Child ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409594

RESUMO

OBJECTIVE: To estimate the impact on early development of prematurity and summer birth and the potential 'double disadvantage' created by starting school a year earlier than anticipated during pregnancy, due to being born preterm. DESIGN, SETTING AND PATIENTS: We investigated the impact of gestational and school-entry age on the likelihood of failing to achieve a 'Good Level of Development' (GLD) on the Early Years Foundation Stage Profile in 5-year-old children born moderate-to-late preterm using data from the Born in Bradford longitudinal birth cohort. We used hierarchical logistic regression to control for chronological maturity, and perinatal and socioeconomic factors. RESULTS: Gestational age and school-entry age were significant predictors of attaining a GLD in the 10 337 children who entered school in the correct academic year given their estimated date of delivery. The odds of not attaining a GLD increased by 1.09 (95% CI 1.06 to 1.11) for each successive week born early and by 1.17 for each month younger within the year group (95% CI 1.16 to 1.18). There was no interaction between these two effects. Children starting school a year earlier than anticipated during pregnancy were less likely to achieve a GLD compared with (1) other children born preterm (fully adjusted OR 5.51 (2.85-14.25)); (2) term summer births (3.02 (1.49-6.79)); and (3) preterm summer births who remained within their anticipated school-entry year (3.64 (1.27-11.48)). CONCLUSIONS: These results confirm the developmental risks faced by children born moderate-to-late preterm, and-for the first time-illustrate the increased risk associated with 'double disadvantage'.

7.
Environ Health Perspect ; 127(8): 87001, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393792

RESUMO

BACKGROUND: Telomere length is a molecular marker of biological aging. OBJECTIVE: Here we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age. METHODS: In a multicenter European birth cohort study, HELIX (Human Early Life Exposome) ([Formula: see text]), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide ([Formula: see text]), particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates. RESULTS: LTL was inversely associated with prenatal and 1-y childhood [Formula: see text] and [Formula: see text] exposures levels. Each standard deviation (SD) increase in prenatal [Formula: see text] was associated with a [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) change in LTL. Prenatal [Formula: see text] was nonsignificantly associated with LTL ([Formula: see text] per SD increase; 95% CI: [Formula: see text], 0.6). For each SD increment in 1-y childhood [Formula: see text] and [Formula: see text] exposure, LTL shortened by [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) and [Formula: see text] (95% CI: [Formula: see text], 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL. CONCLUSION: Lower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. https://doi.org/10.1289/EHP4148.

8.
BMC Public Health ; 19(1): 939, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300003

RESUMO

BACKGROUND: Born in Bradford (BiB) is a prospective multi-ethnic pregnancy and birth cohort study that was established to examine determinants of health and development during childhood and, subsequently, adult life in a deprived multi-ethnic population in the north of England. Between 2007 and 2010, the BiB cohort recruited 12,453 women who experienced 13,776 pregnancies and 13,858 births, along with 3353 of their partners. Forty five percent of the cohort are of Pakistani origin. Now that children are at primary school, the first full follow-up of the cohort is taking place. The aims of the follow-up are to investigate the determinants of children's pre-pubertal health and development, including through understanding parents' health and wellbeing, and to obtain data on exposures in childhood that might influence future health. METHODS: We are employing a multi-method approach across three data collection arms (community-based family visits, school based physical assessment, and whole classroom cognitive, motor function and wellbeing measures) to follow-up over 9000 BiB children aged 7-11 years and their families between 2017 and 2021. We are collecting detailed parent and child questionnaires, cognitive and sensorimotor assessments, blood pressure, anthropometry and blood samples from parents and children. Dual x-ray absorptiometry body scans, accelerometry and urine samples are collected on subsamples. Informed consent is collected for continued routine data linkage to health, social care and education records. A range of engagement activities are being used to raise the profile of BiB and to disseminate findings. DISCUSSION: Our multi-method approach to recruitment and assessment provides an efficient method of collecting rich data on all family members. Data collected will enhance BiB as a resource for the international research community to study the interplay between ethnicity, socioeconomic circumstances and biology in relation to cardiometabolic health, mental health, education, cognitive and sensorimotor development and wellbeing.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Pobreza/etnologia , Determinantes Sociais da Saúde/etnologia , Criança , Inglaterra , Feminino , Seguimentos , Humanos , Masculino , Gravidez , Estudos Prospectivos , Inquéritos e Questionários
9.
Anesthesiology ; 131(3): 477-491, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31166241

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Postoperative delirium and postoperative cognitive dysfunction both occur in a substantial number of older surgical patientsPostoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, although their relationship is unclear WHAT THIS ARTICLE TELLS US THAT IS NEW: Postoperative delirium increased the risk of postoperative cognitive dysfunction at 1 month postoperatively but there was no association between postoperative delirium and cognitive dysfunction at 2 and 6 months after major noncardiac surgeryPostoperative delirium and longer-term postoperative cognitive dysfunction may be different disorders BACKGROUND:: Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up. METHODS: This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method-based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months. RESULTS: One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07-1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72-1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71-2.09). CONCLUSIONS: Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

10.
Pediatr Allergy Immunol ; 30(6): 604-613, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31188509

RESUMO

BACKGROUND: The prevalence of allergic diseases has increased in recent decades, but the causes remain unclear. Changes in the epidemiology of childhood infections could have contributed, but the current evidence is inconclusive. This study aims to investigate whether age at cytomegalovirus (CMV), Epstein-Barr virus (EBV) or varicella zoster virus (VZV) infection is associated with the development of atopy. METHODS: A total of 2559 children were enrolled in the Born in Bradford Allergy and Infection Study. Serum samples collected at 12 and 24 months were tested for CMV-IgG, EBV-IgG and VZV-IgG for 1000 children to establish age at infection. Skin prick testing (SPT) was conducted at age 4 years. RESULTS: Serology and SPT results were available for 740 children. Of these, 135 (18%) were atopic. In girls, there was a strong association of CMV infection in the second year with increased odds of atopy (adjusted OR 4.38, 95% CI 1.87-10.29) but this was not observed in boys. Age at EBV or VZV infection was not associated with risk of atopy in unadjusted analysis, but there was effect modification by sex; girls infected with VZV in the second year of life had increased odds of atopy (adjusted OR 2.85, 95% CI 1.29-6.30). CONCLUSIONS: Our results highlight potential sex-specific effects of age at CMV infection and age at VZV infection on risk of atopy, which provide insight into the mechanisms involved in the development of atopy.

12.
Environ Res ; 174: 95-104, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055170

RESUMO

The human exposome affects child development and health later in life, but its personal external levels, variability, and correlations are largely unknown. We characterized the personal external exposome of pregnant women and children in eight European cities. Panel studies included 167 pregnant women and 183 children (aged 6-11 years). A personal exposure monitoring kit composed of smartphone, accelerometer, ultraviolet (UV) dosimeter, and two air pollution monitors were used to monitor physical activity (PA), fine particulate matter (PM2.5), black carbon, traffic-related noise, UV-B radiation, and natural outdoor environments (NOE). 77% of women performed the adult recommendation of ≥150 min/week of moderate to vigorous PA (MVPA), while only 3% of children achieved the childhood recommendation of ≥60 min/day MVPA. 11% of women and 17% of children were exposed to daily PM2.5 levels higher than recommended (≥25µg/m3). Mean exposure to noise ranged from Lden 51.1 dB in Kaunas to Lden 65.2 dB in Barcelona. 4% of women and 23% of children exceeded the recommended maximum of 2 Standard-Erythemal-Dose of UV-B at least once a week. 33% of women and 43% of children never reached the minimum NOE contact recommendation of ≥30 min/week. The variations in air and noise pollution exposure were dominated by between-city variability, while most of the variation observed for NOE contact and PA was between-participants. The correlations between all personal exposures ranged from very low to low (Rho < 0.30). The levels of personal external exposures in both pregnant women and children are above the health recommendations, and there is little correlation between the different exposures. The assessment of the personal external exposome is feasible but sampling requires from one day to more than one year depending on exposure due to high variability between and within cities and participants.

13.
J Autism Dev Disord ; 49(8): 3113-3126, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31055684

RESUMO

The use of robots to teach students with autism spectrum disorder communication skills has basis in the literature; however, research investigating the effects of teaching coding or programming of robotics to promote learning in STEM to this population has not yet been conducted. The purpose of the current study was to evaluate the effects of teaching one code explicitly, using model-lead-test on the following dependent variables: (a) acquisition of the explicitly-taught code (i.e., robotic movement); (b) generalization of the explicitly-taught code to other novel codes (i.e., robotic sounds, light effects, complex movements), and (c) self-generated novel sets of codes. Results of the multiple probe across participants design demonstrate that all three students with ASD and challenging behaviors were able to acquire the initial code, generalize the initial code to novel codes, and self-generate (i.e., create, test, and evaluate) their own coding. Implications for practitioners, study limitations, and recommendations for future research are discussed.

14.
Biol Sex Differ ; 10(1): 23, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060622

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence in the developed world, and affects women to a greater degree than men. In the USA, the growth of knee OA has been paralleled by an increase in rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, postoperative trajectories of pain vary widely, with some patients reporting a complete absence of pain, but with a significant minority reporting worsening pain. Biopsychosocial factors, including anxiety and depression, are known to contribute importantly to the experience of joint pain, with women reporting a higher degree of negative affective symptoms. METHODS: This study investigated sex differences in TKA outcomes in age-matched groups of men and women at two academic medical centers. Pain and physical function were assessed in 100 patients (50 men and 50 women) during the perioperative period (preoperative visit-6 weeks postsurgical). The association of preoperative negative affect (anxiety and depression scores) to postoperative pain and function was evaluated, with specific attention to sex differences in this relationship. RESULTS: Overall, women reported more baseline pain-related physical dysfunction (although not higher baseline pain scores), as well as higher acute postoperative pain scores during the 2 weeks following TKA than their male counterparts. By 6 weeks postoperatively, sex differences in reported pain were no longer evident. Interestingly, although women reported higher preoperative levels of emotional distress than men, preoperative anxiety and depression scores were better predictors of severe postoperative pain among men than women, throughout the postoperative test period. CONCLUSIONS: This study underlines the importance of considering sex and psychosocial factors, as well as their interaction, in understanding postsurgical pain trajectories.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31028168

RESUMO

INTRODUCTION: Insertion of intrauterine methods of contraception (IUC) carries an inherent but small risk of perforation of the uterus, usually quoted at 2 in 1000. If perforation occurs, it is usually discovered either when a patient presents with 'missing threads' or with an unplanned pregnancy. Rarely, if the IUC has perforated bowel, patients can present acutely unwell although this sometimes occurs years after insertion. Asymptomatic perforation of the bowel (with IUC insertion or otherwise) is not common. CASE HISTORY: In January 2018, a 41-year-old woman attended our community sexual and reproductive health service requesting removal of her intrauterine system (IUS). The clinic nurse performed this and during the consultation the patient revealed that several days earlier she had passed a previous 'lost' intrauterine device (IUD) when she opened her bowels. She came to believe this was an IUD inserted in 2006 that had been 'lost' and resulted in a pregnancy with her third child. We counselled her about her options and she had the IUS removed as she was worried this could happen again and opted to use condoms. CONCLUSION: This case reports an unusual presentation of a delayed and importantly 'silent' perforation of the uterus and bowel on insertion of IUC. The case highlights the importance of cross-specialty communication when an IUD has perforated or expelled resulting in a continuing pregnancy, so that appropriate imaging can be arranged following delivery of the baby.

16.
Environ Health Perspect ; 127(4): 47007, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31009264

RESUMO

BACKGROUND: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. OBJECTIVE: We evaluated the association of the urban exposome with birth weight. METHODS: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associations with either continuous birth weight or term low birth weight (TLBW) risk, we primarily relied on the Deletion-Substitution-Addition (DSA) algorithm, which is an extension of the stepwise variable selection method. Second, we used an exposure-by-exposure exposome-wide association studies (ExWAS) method accounting for multiple hypotheses testing to report associations not adjusted for coexposures. RESULTS: The most consistent statistically significant associations were observed between increasing green space exposure estimated as Normalized Difference Vegetation Index (NDVI) and increased birth weight and decreased TLBW risk. Furthermore, we observed statistically significant associations among presence of public bus line, land use Shannon's Evenness Index, and traffic density and birth weight in our DSA analysis. CONCLUSION: This investigation is the first large urban exposome study of birth weight that tests many environmental urban exposures. It confirmed previously reported associations for NDVI and generated new hypotheses for a number of built-environment exposures. https://doi.org/10.1289/EHP3971.

17.
Head Neck Pathol ; 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30972634

RESUMO

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss' kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons' responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.

18.
Emerg Med J ; 36(4): 208-212, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30940680

RESUMO

OBJECTIVE: To compare outcome of clinical advice given by emergency physicians (EPs) versus non-physician clinical advisors (NPCAs) on a UK National Health Service 111 centre. METHOD: This was a prospective study conducted between July 2016 and February 2017. We targeted calls in which call handlers using standard NHS 111 clinical decision support software would have advised the caller to attend a hospital ED. These calls were passed to a clinical assessment service (CAS) and reviewed by either an EP (July to November 2016) or an NPCA (December 2016 to February 2017). RESULTS: During the preintervention year, 80.2% of callers were advised to attend the ED within 1 or 4 hours, 1.2% were referred to out of hours (OOH) primary care and 0.3% to self-care. During the study, call handlers designated 2606 calls as needing to attend the ED in 1 or 4 hours and passed these on to the clinical advisors. There was a reduction of 75%-81% in cases advised to attend the ED in both intervention groups; EPs advised 396 of 1558 callers (25.4%) to attend ED; NPCAs advised 194 of 1048 callers (18.5%) to attend ED. For calls not requiring the ED, EPs recommended self/home care management in 38.1% of these calls, NPCAs recommended self-care for 15.7% (difference=22.4%; 95% CI 19.0% to 25.7%). EPs recommended 4.5% to attend OOH primary care, while NPCAs recommended OOH primary care for 42.1% (difference=37.6%, 95% CI 34.3% to 40.8%). CONCLUSIONS: A CAS within NHS 111 using clinicians decreases referrals to the ED. EPs use fewer services and resources. Further work needs to be undertaken to determine the workforce skill mix for an NHS 111 CAS.


Assuntos
Consultores , Medicina de Emergência , Serviço Hospitalar de Emergência/organização & administração , Padrões de Prática Médica/estatística & dados numéricos , Telefone , Triagem/métodos , Algoritmos , Técnicas de Apoio para a Decisão , Inglaterra , Humanos , Estudos Prospectivos , Medicina Estatal
19.
Oral Surg Oral Med Oral Pathol Oral Radiol ; 128(3): e113-e121, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30928327

RESUMO

Ameloblastic carcinoma is a rare odontogenic neoplasm that demonstrates the histologic characteristics of ameloblastoma, accompanied by the cytologic features of malignancy. The spindle-cell variant of ameloblastic carcinoma (SCAC) is exceptionally rare, with a total of 10 cases having been reported in the literature to date. Histologically, a prominent sarcomatoid cell population appears to originate from the epithelial (ameloblastic) component. Like conventional ameloblastic carcinoma, most cases of SCAC occur in individuals older than 40 years of age. Here, 3 additional cases of SCAC are reported, 2 of which occurred in young individuals. Diagnostic criteria to aid in the identification of SCAC are proposed. Finally, histologic and immunohistochemical evidence supporting the occurrence of epithelial-mesenchymal transition in SCAC is presented.

20.
Int J Hyg Environ Health ; 222(5): 864-872, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31010791

RESUMO

BACKGROUND: Human exposure to environmental chemical contaminants at critical periods of development can lead to lifelong health consequences. Traditionally, socioeconomically disadvantaged groups are thought to experience higher contaminant exposures; however, this relationship may not hold for all contaminants. METHODS: Using data from six European birth cohorts (1301 mother-child pairs), we determined biomarkers of exposure to 41 contaminants in biological samples from children (6-12 years) and their mothers during pregnancy, including organochlorine compounds (OCs), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFASs), metals, phthalate metabolites, phenols, and organophosphate (OP) pesticide metabolites. We analyzed these biomarkers with several socioeconomic position (SEP) indicators (maternal education, employment status and family affluence scale). RESULTS: Higher SEP was associated with higher concentrations of several chemicals during pregnancy, including certain PFASs, mercury, arsenic, several phenols, and OP pesticides. Similarly, childhood concentrations of OCs, PFASs, mercury, arsenic, and bisphenol A were higher in higher SEP groups. Conversely, cadmium exposure during pregnancy and exposure to lead and phthalate metabolites in childhood were higher in lower SEP. Principal components representing multiple pollutant exposures showed similar association with SEP. CONCLUSIONS: This study demonstrates that environmental chemical contaminant exposure during fetal and childhood life is not exclusively associated to lower SEP and that for several contaminants higher SEP groups incur higher exposure levels.

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