Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery.

BACKGROUND: While fetal growth is a tightly regulated process, it is sensitive to environmental exposures that occur during pregnancy. Many commonly used consumer products contain chemicals that can disturb processes underlying fetal growth. However, mixtures of these chemicals have been minimally examined. We investigated associations between prenatal exposure to 33 consumer product chemicals (nine organophosphate ester flame retardant [OPE] metabolites, 12 phthalate metabolites, and 12 phenols) and the odds of small- or large-for-gestational age (SGA and LGA) births. METHODS: This case-control study was comprised of SGA (N = 31), LGA (N = 28), and appropriate for gestational age control (N = 31) births selected from the larger LIFECODES cohort. Biomarkers of exposure to consumer product chemicals were quantified in maternal urine collected from up to three study visits during pregnancy. In a single-pollutant approach, odds ratios (OR) and 95% confidence intervals (CI) of SGA and LGA associated with an interquartile range (IQR)-increase in exposure biomarkers were estimated using multinomial logistic regression. In a multi-pollutant approach, quantile g-computation was used to jointly estimate the OR (95% CI) of SGA and LGA per simultaneous one quartile-change in all biomarkers belonging to each chemical class. RESULTS: Among the 33 biomarkers analyzed, 20 were detected in at least 50% of the participants. After adjusting for potential confounders, we observed reduced odds of LGA in association with higher urinary concentrations of several exposure biomarkers. For example, an IQR-increase in the OPE metabolite, diphenyl phosphate, was associated with lower odds of LGA (OR: 0.40 [95% CI: 0.18, 0.87]). Using quantile g-computation, we estimated lower odds of an LGA birth for higher OPE metabolite concentrations (OR: 0.49 [95% CI: 0.27, 0.89]) and phthalate metabolite concentrations (OR: 0.23 [95% CI: 0.07, 0.73]). Associations between consumer product chemicals and SGA were largely null. CONCLUSIONS: Joint exposure to OPEs and phthalates was associated with lower odds of delivering LGA. Associations with LGA could indicate a specific impact of these exposures on the high end of the birth weight spectrum. Future work to understand this nuance in the associations between consumer product chemical mixtures and fetal growth is warranted.

Indian agriculture, air pollution, and public health in the age of COVID.

Emerging evidence supports the intuitive link between chronic health conditions associated with air pollution and the vulnerability of individuals and communities to COVID-19. Poor air quality already imposes a highly significant public health burden in Northwest India, with pollution levels spiking to hazardous levels in November and early December when rice crop residues are burned. The urgency of curtailing the COVID-19 pandemic and mitigating a potential resurgence later in the year provides even more justification for accelerating efforts to dramatically reduce open agricultural burning in India.

Impact of mapping points in high-density mapping of the left atrium.

PURPOSE: Currently, high-density mapping techniques are being discussed for more precise voltage mapping, lesion validation after pulmonary vein isolation (PVI) and superior left atrial tachycardia (LAT) mapping. However, the quality of high-density maps varies according to different mapping systems, multipolar catheter (MPC) types and numbers of mapping points. The aim of this study was to evaluate the impact of different numbers of mapping points in high-density mapping on validity. METHODS: From February 2016 to August 2018, 154 patients with previous PVI ablation and recurrent atrial fibrillation (AF) or left atrial tachycardia (LAT) were mapped by Orion™ multipolar catheter and Rhythmia HDx™ mapping system at our centre. Of those, 90 maps from 25 patients [11 male patients/14 female patients; age 76 ± 12 years] with 8000 to 16,000 mapping points in the primary map were collected. All maps were evaluated offline by two independent and blinded electrophysiologists regarding the following issues: (1) Is PVI observable in all veins? (2) Does voltage map cover the whole left atrium? (3) Does activation map display one or more isthmuses? The 90 maps consist of 30 maps with deactivated 24 of 64 electrodes of MPC with < 1000 mapping points (A), 30 maps with deactivated 16 of 64 electrodes of MPC and 2000 to 6000 mapping points (B) and 30 primary maps with 8000 to 16,000 mapping points (C). RESULTS: For (A), only in one map (3.3%), for (B) in 20 maps (66.7%, p < 0.05) and for (C) in 24 maps (80%) both investigators agreed with evaluable PVI in all veins. Investigators were able to assess whether the voltage map covered the whole left atrium and the same low voltage areas in (A) in 0 maps, in (B) in 16 maps (53%, p < 0.05) and in (C) in 23 maps (77%, p < 0.05). Also, investigators were able to locate the same critical isthmuses in the activation maps in (A) in 0 maps, in (B) in 2 maps (7%) and in (C) in 20 maps (67%, p < 0.05). CONCLUSIONS: In order to achieve comparable high-density maps which are verified by independent investigators, a minimum of 2000 to 6000 mapping points are required in the majority of voltage maps to evaluate PVI and low voltage areas. To define the critical isthmuses in activations maps, 8000 mapping points or more might be necessary. High-density maps with more than 8000 points increase the interrater reliability.

Sleepless and desynchronized: Impaired inter trial phase coherence of steady-state potentials following sleep deprivation.

Sleep loss has detrimental effects on cognitive and emotional functioning. These impairments have been associated with alterations in EEG measures of power spectrum and event-related potentials, however the impact of sleep loss on inter trial phase coherence (ITPC), a measure of phase consistency over experimental trials, remains mostly unknown. ITPC is thought to reflect the ability of the neural response to temporally synchronize with relevant events, thus optimizing information processing. In the current study we investigated the effects of sleep deprivation on information processing by evaluating the phase consistency of steady-state visual evoked potentials (ssVEPs) as well as amplitude-based measures of ssVEPs, obtained from a group of 18 healthy individuals following 24 h of total sleep deprivation and after a night of habitual sleep. An ssVEP task was utilized, which included the presentation of dots flickering at 7.5 Hz, along with a cognitive-emotional task. Our results show that ITPC is significantly reduced under sleep deprivation relative to habitual sleep. Interestingly, decreased ITPC under sleep deprivation was associated with decreased behavioral performance in the psychomotor vigilance task (PVT), a validated measure of reduced vigilance following a lack of sleep. The results suggest that the capability of the brain to synchronize with rhythmic stimuli is disrupted without sleep. Thus, decreased ITPC may represent an objective and mechanistic measure of sleep loss, allowing future work to study the relation between brain-world synchrony and the specific functional impairments associated with sleep deprivation.

Using record linkage to examine testing patterns for respiratory viruses among children born in Western Australia.

Changes in respiratory pathogen testing can affect disease burden estimates. Using linked data, we describe changes in respiratory virus testing among children born in Western Australia in 1996-2012. We extracted data on respiratory specimens from these children from birth to age 9 years. We estimated testing rates by age, year, Aboriginal status and geographical location. Predictors of testing among children hospitalised at least once before their 10th birthday were identified using logistic regression. We compared detection methods for respiratory viruses from nasal/nasopharyngeal (NP) specimens by age and year. Of 83 199 virology testing records in 2000-2012, 80% were nasal/NP specimens. Infants aged <1 month had the highest testing rates. Testing rates in all children increased over the study period with considerable yearly fluctuations. Among hospitalised children, premature children <32 weeks gestation had over three times the odds of being tested (95% CI 3·47-4·13) than those born at term. Testing using molecular methods increased from 5% to 87% over the study period. Proportion of positive samples increased from 36·3% to 44·4% (P < 0·01); this change was greatest in children aged 2-9 years. These findings will assist in interpreting results from future epidemiology studies assessing the pathogen-specific burden of disease.

Clostridium difficile infection diagnosis in a paediatric population: comparison of methodologies.

The increasing incidence of Clostridium difficile infection (CDI) in paediatric hospitalised populations, combined with the emergence of hypervirulent strains, community-acquired CDI and the need for prompt treatment and infection control, makes the rapid, accurate diagnosis of CDI crucial. We validated commonly used C. difficile diagnostic tests in a paediatric hospital population. From October 2011 to January 2012, 150 consecutive stools were collected from 75 patients at a tertiary paediatric hospital in Perth, Western Australia. Stools were tested using: C. Diff Quik Chek Complete, Illumigene C. difficile, GeneOhm Cdiff, cycloserine cefoxitin fructose agar (CCFA) culture, and cell culture cytotoxin neutralisation assay (CCNA). The reference standard was growth on CCFA or Cdiff Chromagar and PCR on isolates to detect tcdA, tcdB, cdtA, and cdtB. Isolates were PCR ribotyped. The prevalence of CDI was high (43 % of patients). Quik Chek Complete glutamate dehydrogenase (GDH) demonstrated a low negative predictive value (NPV) (93 %). Both CCNA and Quik Chek Complete toxin A/B had poor sensitivity (33 % and 29 % respectively). Molecular methods both had 89 % sensitivity. Algorithms using GDH + Illumigene or GeneOhm reduced the sensitivity to 85 % and 83 % respectively. Ribotype UK014/20 predominated. GDH NPV and GeneOhm and Illumigene sensitivities were reduced compared with adult studies. Quik Chek Complete and CCNA cannot reliably detect toxigenic CDI. A GDH first algorithm showed reduced sensitivity. In a high prevalence paediatric population, molecular methods alone are recommended over the use of GDH algorithm or culture and CCNA, as they demonstrate the best test performance characteristics.

Effects of cross-modal selective attention on the sensory periphery: cochlear sensitivity is altered by selective attention.

There is increasing evidence that alterations in the focus of attention result in changes in neural responding at the most peripheral levels of the auditory system. To date, however, those studies have not ruled out differences in task demands or overall arousal in explaining differences in responding across intermodal attentional conditions. The present study sought to compare changes in the response of cochlear outer hair cells, employing distortion product otoacoustic emissions (DPOAEs), under different, balanced conditions of intermodal attention. DPOAEs were measured while the participants counted infrequent, brief exemplars of the DPOAE primary tones (auditory attending), and while counting visual targets, which were instances of Gabor gradient phase shifts (visual attending). Corroborating an earlier study from our laboratory, the results show that DPOAEs recorded in the auditory-ignoring condition were significantly higher in overall amplitude, compared with DPOAEs recorded while participants attended to the eliciting primaries; a finding in apparent contradiction with more central measures of intermodal attention. Also consistent with our previous findings, DPOAE rapid adaptation, believed to be mediated by the medial olivocochlear efferents (MOC), was unaffected by changes in intermodal attention. The present findings indicate that manipulations in the conditions of attention, through the corticofugal pathway, and its last relay to cochlear outer hair cells (OHCs), the MOC, alter cochlear sensitivity to sound. These data also suggest that the MOC influence on OHC sensitivity is composed of two independent processes, one of which is under attentional control.

SU-E-I-22: Metal Artifact Correction Using KV and Selective MV Imaging.

PURPOSE: To improve the image quality of radiotherapy planning CTs for patients with metal implants or fillings by completing the missing kV projection data with selectively acquired MV data that does not suffer from photon starvation. Using both imaging systems that are available on current radiotherapy devices, streaking artifacts are avoided and the soft tissue contrast is restored, even in areas where the kV photons do not contribute any information. This enables a better delineation of structures of interest in planning CT images for patients with metal objects. METHODS: An algorithm for combining kV and MV projection data from the two on-board imagers of a radiotherapy device is presented in this work. It only requires selective MV imaging with the high energy X-rays being collimated onto the metal implants, ensuring that the patient dose does not increase significantly. The algorithm can cope with non-identical geometries of the two imagers and is based on stitching together kV and MV sinograms by estimating a ratio between them. A numerical head phantom with two dental fillings and two soft tissue patterns was used to quantitatively evaluate the proposed hybrid reconstruction algorithm. A structural similarity index (SSIM) with respect to the ground truth data was computed for two ROIs. Realistic, polychromatic spectra were used for both imagers with 120 keV(p) and 6 MeV(p). The patient dose was limited to about 6 cGy for both acquisitions combined. RESULTS: The reconstruction results yield visually as well as objectively better results (SSIM=74.8%) than a simple sinogram interpolation of the kV data (SSIM=69.7%) or a reconstruction from the original data (SSIM=17.9%). CONCLUSIONS: We have successfully implemented a new reconstruction method for hybrid kV-MV cone beam CT reconstruction that enables a better planning of radiotherapy treatments for patients with metal implants without compromising their safety. This work was funded by NIH grant 1R01CA138426-01A1.

WE-G-217BCD-05: Fiducial Marker-Based Motion Compensation for the Acquisition of 3D Knee Geometry Under Weight-Bearing Conditions Using a C-Arm CT Scanner.

PURPOSE: Imaging the knee under realistic load-bearing conditions can be carried out in a horizontal plane using a C-arm CT scanner. Human subjects can be scanned in a standing position and acquired data successfully reconstructed. However, reconstructing this data is a challenge due to significant artifacts that are induced due to involuntary motion. Here, we propose motion correction methods in 2D and 3D. METHODS: Four volunteers were scanned for 8 seconds while squatting with ∼30 degree flexion. Eight tantalum fiducial markers suitably attached around the knee were used to track motion. The marker position in each projection was semi- automatically detected. Each marker's static 3D position, which served as a reference to correct temporal motion, was estimated by triangulating each marker's 2D position from 248 projections using known projection matrices. Motion was corrected in 3 ways: 1) 2D projection shifting based on the mean position of markers, 2) 2D projection warping using approximate thin- plate splines, 3) 3D rigid body warping. RESULTS: The original reconstruction was severely motion-corrupted which made it impossible to distinguish the boundaries of bones. Reconstruction with projection shifting and warping in 2D improved visualization of edges of soft tissue as well as bone. A simple numerical metric of residual bead deviation from static position was reduced from 3.2mm to 0.4mm. The 2D-based methods are inherently limited in that they cannot fully accommodate different 3D movements at different depths from the X-ray source. Reconstruction with 3D warping shows clearer edges and less streak artifact than the 2D methods. CONCLUSIONS: The proposed three motion correction methods effectively reduced motion-induced artifacts in the reconstruction and are therefore suitable for weight-bearing scanning. Future work includes scanning patients in standing position after contrast injection for evaluating the soft tissue structure and constructing 3D finite element models for the estimation of joint cartilage stress. This study was supported by Center for Biomedical Imaging at Stanford, by Siemens AG, Healthcare Sector, and by the Lucas Foundation at Stanford. The concepts and contents proposed here are based on research and are not commercially available.

Eosinopenia as a diagnostic marker of bloodstream infection in hospitalised paediatric and adult patients: a case-control study.

The objective of this study was to assess whether eosinopenia was a reliable diagnostic marker of bloodstream infection in hospitalised adult and paediatric patients. The design was a case-control study, set in a tertiary adult and paediatric hospital. A total of 157 adult and 85 paediatric patients with bloodstream infection ('cases') were compared to 195 and 94 randomly selected adult and paediatric patients who had clinical suspicion of bloodstream infection but with a negative blood culture ('controls') respectively. Patients with haematological or immunosuppressive disease and control patients who were treated with antibiotics within one week prior to the blood culture were excluded. Eosinopenia, or undetectable eosinophil count (<0.01 x 10(9) or <10/mm3), was more common among the cases than the controls (46.5% vs 21.5%, respectively). The specificity of eosinopenia to predict bloodstream infection in adult patients was reasonable (79%, 95% confidence interval [CI] 74 to 82), but its sensitivity was low (47%, 95% CI 41 to 52). The absolute eosinophil count only had a modest ability to discriminate bloodstream infections from controls in adult patients (area under receiver operating characteristic curve 0.349, 95% CI 0.288 to 0.411). Eosinophil counts had very little overall predictive ability (area under receiver operating characteristic curve 0.448, 95% CI 0.363 to 0.533, P=0.237), and the sensitivity (54%, 95% CI 47 to 61) and specificity (56%, 95% CI 49 to 63) of eosinopenia to predict bloodstream infection in paediatric patients were both low. In the multivariate analyses, only C-reactive protein concentrations and neutrophil counts, but not eosinopenia, were significantly associated with the presence of bloodstream infection in both adult and paediatric patients. The presence of eosinopenia can be considered as an inexpensive warning test for bloodstream infection in hospitalised adult patients so that further investigations can be initiated. An absence of eosinopenia is, however not sensitive enough to exclude bloodstream infection. C-reactive protein concentrations and neutrophil counts were both better markers of bloodstream infection than eosinopenia in hospitalised paediatric and adult patients.

Tracking neonatal nosocomial infection: the continuous quality improvement cycle.

Neonatal nosocomial infection (NNI) is a major complication of neonatal care, increasing mortality, morbidity and the costs of healthcare. Management of NNI involves attention to many details of care, creating a culture of change within a neonatal unit and the implementation of a continuous quality improvement cycle. This paper describes the initiation of a quality improvement team (QIT) and the aspects of infection control bundles that have been implemented. The setting was a single large perinatal centre over a seven-year period. Statistical tracking of NNI in exceedingly premature infants was by control charting methodology. A steady and statistically significant decline in NNI rates from 13 to seven episodes per 1000 bed-days (censored to day 35) for infants less than 29 weeks of gestation has been recorded. A multidisciplinary QIT has managed the implementation of measures designed to reduce NNI in the unit. These have included raising awareness of the need for asepsis, improved hand hygiene, increased vigilance in using central lines, monitoring blood culture collection techniques and improving the environment. We believe such measures in conjunction with the positive feedback obtained from charting have been responsible for the steady decline in NNI. This study is one of the first to close the QIT loop and to demonstrate statistical improvement in NNI through the introduction of specific care bundles.

Bacterial contamination in solution aspirated from non-sterile packaged fentanyl ampoules: a laboratory study.

Iatrogenic meningitis is a rare complication of spinal anaesthesia. It is mandatory to use a technique which minimises the risk of introducing bacteria into the subarachnoid space. Currently available fentanyl ampoules require a careful drawing-up technique, as the outside of the ampoule is not sterile and there is potential to contaminate the contents in the drawing-up process. We designed a pilot laboratory study to determine the extent of bacterial contamination of fentanyl solutions drawn up from non-sterile packaged glass fentanyl ampoules using three different methods: aspirating through a 5 microm filter needle only, aspirating through a 5 microm filter needle after swabbing the neck of the ampoule with isopropyl alcohol and aspirating through an antibacterial filter in addition to the 5 microm filter needle. Ten anaesthetists used each method once, in randomised order to draw up solution from three different fentanyl ampoules. Samples underwent bacterial culture in blood agar and enrichment broth for 48 hours. No significant growth was seen in any sample. This pilot study did not identify any bacterial contamination of fentanyl solution irrespective of which of the three methods for aspiration was used.

Best practice guidelines for the operation of a donor human milk bank in an Australian NICU.

Until the establishment of the PREM Bank (Perron Rotary Express Milk Bank) donor human milk banking had not occurred in Australia for the past 20 years. In re-establishing donor human milk banking in Australia, the focus of the PREM Bank has been to develop a formal and consistent approach to safety and quality in processing during the operation of the human milk bank. There is currently no existing legislation in Australia that specifically regulates the operation of donor human milk banks. For this reason the PREM Bank has utilised existing and internationally recognised management practices for managing hazards during food production. These tools (specifically HACCP) have been used to guide the development of Standard Operating Procedures and Good Manufacturing Practice for the screening of donors and processing of donor human milk. Donor screening procedures are consistent with those recommended by other human milk banks operating internationally, and also consistent with the requirements for blood and tissue donation in Australia. Controlled documentation and record keep requirements have also been developed that allow complete traceability from individual donation to individual feed dispensed to recipient and maintain a record of all processing and storage conditions. These operational requirements have been developed to reduce any risk associated with feeding pasteurised donor human milk to hospitalised preterm or ill infants to acceptable levels.

Direct comparison of enzyme measurements from dried blood and leukocytes from male and female Fabry disease patients.

Anderson-Fabry disease is an X-linked disorder that is caused by deficiency of the lysosomal enzyme alpha-galactosidase A. Symptoms include chronic progressive painful small-fibre neuropathy, cornea verticillata, renal failure and heart disease. Interestingly, female heterozygous patients may also show severe symptoms. After clinical suspicion, usually the determination of alpha-galactosidase activity in leukocytes is requested first. Alternatively, an enzymatic assay using dried blood specimens has been described. Dried blood samples require less material and are substantially more stable (several months at room temperature) than whole-blood specimens. To validate the new method and to asses its usefulness for diagnosis of female patients, enzyme activities of alpha-galactosidase, beta-galactosidase and beta-glucuronidase from 78 known Fabry patients were compared (29 males, 47 females) between both materials. In summary, the determination of alpha-galactosidase activity using dried blood and leukocytes as well as the ratio of alpha-galactosidase to beta-glucuronidase in dried blood can improve the diagnostic specificity in cases of female patients who are difficult to identify when only leukocyte enzyme activities are considered.

Programa de atención musculoesquelética (PAME) en atención primaria: propuesta y diseño / Program of musculoskeletal attention in primare care: proposal and design

Las enfermedades musculoesqueléticas (EME), constituyen un grupo importante de patologías de alta prevalencia en nuestro país, capaces de afectar la calidad de vida, produciendo dolor y limitación funcional en las actividades de la vida diaria, principalmente en mujeres y adultos mayores. Su sintomatología asociada, se caracteriza por su cronicidad y su capacidad de generar demanda asistencial. La gran mayoría de los problemas musculoesqueléticos que hoy no tienen acceso a la atención especializada, reflejada en largas listas de espera al nivel secundario, corresponden a patología degenerativa de manejo generalmente conservador. Hoy en día no existe un programa estructurado desde el nivel central que de cuenta del acceso a este problema de salud. Durante los años 2005-2006, en el Servicio de Salud Metropolitano Sur, se desarrolló un piloto de atención musculoesquelética (llamado PAME), basado en estrategias de articulación de la red asistencial y de aumento de la resolutividad de la Atención Primaria. Se crearon flujogramas de manejo y derivación médica de las principales patologías involucradas, y se implementó una sala de manejo kinésico, en un consultorio de Atención Primaria. El presente artículo pretender dar cuenta del diseño, áreas e indicadores de evaluación, propuestos para el piloto mencionado. El PAME, espera constituirse en una estrategia válida para cumplir con el objetivo sanitario señalado para la década 2000-2010, del ítem osteomuscular, respondiendo además a las GES 2006-2007 (garantías explícitas de salud de artrosis de rodilla, cadera, hernia del núcleo pulposo y ayudas técnicas). La inserción del PAME preferentemente en Atención Primaria, permitirá desarrollar los ámbitos preventivos y promocionales de las EME.

The ratio of alpha-galactosidase to beta-glucuronidase activities in dried blood for the identification of female Fabry disease patients.

Female heterozygous patients with Fabry disease are difficult to identify because of the relatively high residual activity of alpha-galactosidase. We systematically evaluated the activities of various lysosomal enzymes in dried blood samples from Fabry patients and found that the beta-glucuronidase activity was frequently elevated. The ratio of alpha-galactosidase to beta-glucuronidase proved to be a helpful tool for the diagnosis of female Fabry disease patients.

One set of sounds, two tonotopic maps: exploring auditory cortex with amplitude-modulated tones.

OBJECTIVE: The possibility of simultaneously observing activation of primary and secondary auditory cortices has been demonstrated by Engelien et al. [Hear Res 2000;148:153-60]. METHODS: Such a dual monitoring by means of neuromagnetic recordings can be achieved when a subject is stimulated by brief pulses of 40Hz-modulated tones. Depending on the frequency filter applied, either the steady-state field (SSF) or the N1m can be extracted from the evoked magnetic field complex. RESULTS: Using this "combined" (two-maps) paradigm with 4 carrier frequencies, we show that it is possible to synchronously screen two tonotopic maps--one map each reflected either by the SSF or the N1m. Indicators are the systematic variation in the location (higher frequencies are more posterior) and orientation (higher frequencies oriented differently in the sagittal plane) of the equivalent current dipole (ECD). These parameters were compared with those obtained from "classic" (one map) paradigms in which either a pure tone elicits an N1m or a 40 Hz continuous (3 s) stimulation produces an SSF. Overall the results were similar, however, systematic differences between the paradigms were found for ECD localization, dipole strength, amplitude, and phase. CONCLUSIONS AND SIGNIFICANCE: One possible interpretation of these results is that different tonotopically arranged cortical fields were involved in the generation of the components.