Search

Ischaemic brain infarction can occur without acute neurological symptoms (covert strokes) or with symptoms (overt strokes), both associated with poor health outcomes. We conducted a pilot study of the incidence of preoperative and postoperative (intraoperative or postoperative) covert strokes, and explored the relationship of postoperative ischaemic brain injury to blood levels of neurofilament light, a biomarker of neuronal damage.We analysed 101 preoperative (within 2 weeks of surgery) and 58 postoperative research MRIs on postoperative days 2-9 from two prospective cohorts collected at the University of Wisconsin (NCT01980511 and NCT03124303). Participants were aged65 yr and undergoing non-intracranial, non-carotid surgery.Preoperative covert stroke was identified in 2/101 participants (2%; Bayesian 95% confidence interval [CI], 0.2-5.4). This rate was statistically different from the postoperative ischaemic brain injury rate of 7/58 (12%, 4.9-21.3%; P=0.01) based on postoperative imaging. However, in a smaller group of participants with paired imaging (n=30), we did not identify the same effect (P=0.67). Patients with postoperative brain injury had elevated peak neurofilament light levels (median [inter-quartile range], 2.34 [2.24-2.64] logAlthough limited by a small sample size, these data suggest that preoperative covert stroke occurs more commonly than previously anticipated. Plasma neurofilament light is a potential screening biomarker for postoperative ischaemic brain injury.

Case-control studies have associated delirium with blood-brain barrier (BBB) permeability. However, this approach cannot determine whether delirium is attributable to high pre-existing permeability or to perioperative changes. We tested whether perioperative changes in cerebrospinal fluid/plasma albumin ratio (CPAR) and plasma S100B were associated with delirium severity.Participants were recruited to two prospective cohort studies of non-intracranial surgery (NCT01980511, NCT03124303, and NCT02926417). Delirium severity was assessed using the Delirium Rating Scale-98. Delirium incidence was diagnosed with the 3D-Confusion Assessment Method (3D-CAM) or CAM-ICU (CAM for the ICU). CSF samples from 25 patients and plasma from 78 patients were analysed for albumin and S100B. We tested associations between change in CPAR (n=11) and S100B (n=61) and delirium, blood loss, CSF interleukin-6 (IL-6), and CSF lactate.The perioperative increase in CPAR and S100B correlated with delirium severity (CPAR ρ=0.78, P=0.01; S100B ρ=0.41, P0.001), delirium incidence (CPAR P=0.012; S100B P0.001) and CSF IL-6 (CPAR ρ=0.66 P=0.04; S100B ρ=0.75, P=0.025). Linear mixed-effect analysis also showed that decreased levels of S100B predicted recovery from delirium symptoms (P=0.001). Linear regression demonstrated that change in plasma S100B was independently associated with surgical risk, cardiovascular surgery, blood loss, and hypotension. Blood loss also correlated with CPAR (ρ=0.64, P=0.04), S100B (ρ=0.70, P0.001), CSF lactate (R=0.81, P=0.01), and peak delirium severity (ρ=0.36, P=0.01).Postoperative delirium is associated with a breakdown in the BBB. This increased permeability is dynamic and associated with a neuroinflammatory and lactate response. Strategies to mitigate blood loss may protect the BBB.

The inclusion of engineering in science learning standards draws attention to the need to support pre-service teachers’ ability to teach engineering to young learners. The purpose of this study was...

BACKGROUND: Myocardial and neuronal injury occur commonly after noncardiac surgery. We examined whether patients who had perioperative myocardial injury (PMI) also incurred neuronal injury, and whether myocardial and neuronal injury were associated with similar changes in inflammatory markers or overlapping clinical predictors. METHODS: A total of 114 individuals >65 yr old were recruited from two ongoing perioperative cohort studies (NCT02926417; NCT03124303). Plasma samples were collected before and daily after surgery to process assays for troponin I (PMI), neurofilament light (NfL; neuronal injury) and multiplexed plasma cytokines (inflammation). The primary outcome was the change in NfL in individuals with PMI (>40 pg ml(−1) increase in troponin above preoperative values). We conducted logistic regression to identify if there were shared clinical predictors for myocardial and neuronal injury. RESULTS: Ninety-six patients had paired NfL and troponin data. Twenty-three of 94 subjects (24%) with PMI had greater increases in NfL (median [inter-quartile range, IQR]: 29 pg ml(−1) [3–95 pg ml(−1)]; 2.8-fold increase) compared with subjects with no troponin increase (8 pg ml(−1) [3–20]; 1.3-fold increase; P=0.008). PMI was associated with increased interleukin (IL)-1ra (P=0.005), IL-2 (P=0.045), IL-8 (P=0.002), and IL-10 (P

BACKGROUND: Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium. METHODS: A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity. RESULTS: GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P

Altered predictive coding may underlie the reduced auditory mismatch negativity amplitude observed in patients with dementia. We hypothesized that accumulating dementia-associated pathologies, including amyloid and tau, lead to disturbed predictions of our sensory environment. This would manifest as increased reliance on ‘observed’ sensory information with an associated increase in feedforward, and decrease in feedback, signalling. To test this hypothesis, we studied a cross-sectional cohort of participants who underwent PET imaging and high-density EEG during an oddball paradigm, and used dynamic casual modelling and Bayesian statistics to make inferences about the neuronal architectures (generators) and mechanisms (effective connectivity) underlying the observed auditory-evoked responses. Amyloid-β imaging with [C-11] Pittsburgh Compound-B PET was qualitatively rated using established criteria. Tau-positive PET scans, with [F-18]MK-6240, were defined by an MK-6240 standardized uptake value ratio positivity threshold at 2 standard deviations above the mean of the Amyloid(–) group in the entorhinal cortex (entorhinal MK-6240 standardized uptake value ratio > 1.27). The cross-sectional cohort included a total of 56 participants [9 and 13 participants in the Tau(+) and Amyloid(+) subgroups, respectively: age interquartile range of (73.50–75.34) and (70.5–75.34) years, 56 and 69% females, respectively; 46 and 43 participants in the Tau(−) and Amyloid(−) subgroups, respectively: age interquartile range of (62.72–72.5) and (62.64–72.48) years, 67 and 65% females, respectively]. Mismatch negativity amplitudes were significantly smaller in Tau+ subgroup than Tau− subgroup (cluster statistics corrected for multiple comparisons: P = 0.028). Dynamic causal modelling showed that tau pathology was associated with increased feedforward connectivity and decreased feedback connectivity, with increased excitability of superior temporal gyrus but not inferior frontal regions. This effect on superior temporal gyrus was consistent with the distribution of tau disease on PET in these participants, indicating that the observed differences in mismatch negativity reflect pathological changes evolving in preclinical dementia. Exclusion of participants with diagnosed mild cognitive impairment or dementia did not affect the results. These observational data provide proof of concept that abnormalities in predictive coding may be detected in the preclinical phase of Alzheimer’s disease. This framework also provides a construct to understand how progressive impairments lead to loss of orientation to the sensory world in dementia. Based on our modelling results, plus animal models indicating that Alzheimer’s disease pathologies produce hyperexcitability of higher cortical regions through local disinhibition, mismatch negativity might be a useful monitor to deploy as strategies that target interneuron dysfunction are developed.

BACKGROUND: How conscious experience becomes disconnected from the environment, or disappears, across arousal states is unknown. We sought to identify the neural correlates of sensory disconnection and unconsciousness using a novel serial awakening paradigm. METHODS: Volunteers were recruited for sedation with dexmedetomidine i.v., propofol i.v., or natural sleep with high-density EEG monitoring and serial awakenings to establish whether subjects were in states of disconnected consciousness or unconsciousness in the preceding 20 s. The primary outcome was classification of conscious states by occipital delta power (0.5–4 Hz). Secondary analyses included derivation (dexmedetomidine) and validation (sleep/propofol) studies of EEG signatures of conscious states. RESULTS: Occipital delta power differentiated disconnected and unconscious states for dexmedetomidine (area under the curve [AUC] for receiver operating characteristic 0.605 [95% confidence interval {CI}: 0.516; 0.694]) but not for sleep/propofol (AUC 0.512 [95% CI: 0.380; 0.645]). Distinct source localised signatures of sensory disconnection (AUC 0.999 [95% CI: 0.9954; 1.0000]) and unconsciousness (AUC 0.972 [95% CI: 0.9507; 0.9879]) were identified using support vector machine classification of dexmedetomidine data. These findings generalised to sleep/propofol (validation data set: sensory disconnection [AUC 0.743 {95% CI: 0.6784; 0.8050}]) and unconsciousness (AUC 0.622 [95% CI: 0.5176; 0.7238]). We identified that sensory disconnection was associated with broad spatial and spectral changes. In contrast, unconsciousness was associated with focal decreases in activity in anterior and posterior cingulate cortices. CONCLUSIONS: These findings may enable novel monitors of the anaesthetic state that can distinguish sensory disconnection and unconsciousness, and these may provide novel insights into the biology of arousal. CLINICAL TRIAL REGISTRATION: NCT03284307.

BACKGROUND: Asthma is a common respiratory disorder with a highly heterogeneous nature that remains poorly understood. The objective was to use whole genome sequencing (WGS) data to identify regions of common genetic variation contributing to lung function in individuals with a diagnosis of asthma. METHODS: WGS data were generated for 1,053 individuals from trios and extended pedigrees participating in the family-based Genetic Epidemiology of Asthma in Costa Rica study. Asthma affection status was defined through a physician’s diagnosis of asthma, and most participants with asthma also had airway hyperresponsiveness (AHR) to methacholine. Family-based association tests for single variants were performed to assess the associations with lung function phenotypes. RESULTS: A genome-wide significant association was identified between baseline FEV(1)/FVC ratio and a single-nucleotide polymorphism in the top hit cysteine-rich secretory protein LCCL domain-containing 2 (CRISPLD2) (rs12051168; P = 3.6 × 10(−8) in the unadjusted model) that retained suggestive significance in the covariate-adjusted model (P = 5.6 × 10(−6)). Rs12051168 was also nominally associated with other related phenotypes: baseline FEV(1) (P = 3.3 × 10(−3)), postbronchodilator (PB) FEV(1) (7.3 × 10(−3)), and PB FEV(1)/FVC ratio (P = 2.7 × 10(−3)). The identified baseline FEV(1)/FVC ratio and rs12051168 association was meta-analyzed and replicated in three independent cohorts in which most participants with asthma also had confirmed AHR (combined weighted z-score P = .015) but not in cohorts without information about AHR. CONCLUSIONS: These findings suggest that using specific asthma characteristics, such as AHR, can help identify more genetically homogeneous asthma subgroups with genotype-phenotype associations that may not be observed in all children with asthma. CRISPLD2 also may be important for baseline lung function in individuals with asthma who also may have AHR.

This study aims to describe the psychological needs in children with celiac disease (CD) and to examine the feasibility of psychological consultation in a multidisciplinary clinic. Participants (N = 69) included children with CD and their parents who completed a pre-clinic mental health survey and a 30-min psychological consultation as part of a multidisciplinary clinic (including gastroenterology, nutrition, education, neurology, and neuropsychology). Quantitative and qualitative analyses examined psychological needs, experiences, and satisfaction. The psychologist identified clinically significant symptoms and provided referrals in 49% of children. There were no significant differences by time since CD diagnosis. During the psychology consultation, families discussed emotional adjustment, impact on life and physical well-being, and management of the gluten-free diet. Parents reported high levels of satisfaction from the clinic visit. We identified frequent psychological needs in pediatric CD. The multidisciplinary approach may be a feasible model for specialized, optimal treatment in this population.

Background Cerebral folate deficiency (CFD) syndrome is characterised by a low concentration of 5-methyltetrahydrofolate in cerebrospinal fluid, while folate levels in plasma and red blood cells are in the low normal range. Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha, FRα), DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter) have been previously identified in patients with CFD.Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios.Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Using 48 sporadic CFD samples as a validation cohort, we identified three additional rare variants in CIC that are putatively deleterious mutations. Functional analysis indicates that CIC binds to an octameric sequence in the promoter regions of folate transport genes: FOLR1, PCFT and reduced folate carrier (Slc19A1; RFC1). The CIC nonsense variant (p.R353X) downregulated FOLR1 expression in HeLa cells as well as in the induced pluripotent stem cell (iPSCs) derived from the original CFD proband. Folate binding assay demonstrated that the p.R353X variant decreased cellular binding of folic acid in cells.Conclusion This study indicates that CIC loss of function variants can contribute to the genetic aetiology of CFD through regulating FOLR1 expression. Our study described the first mutations in a non-folate pathway gene that can contribute to the aetiology of CFD.

Delirium is associated with cognitive decline and subsequent dementia, and rises in plasma total tau (tTau) and neurofilament light (NfL), providing links to Amyloid-Tau-Neurodegeneration (ATN) pathophysiology. We investigated whether changes in delirium severity after surgery correlated with changes in cerebrospinal fluid (CSF) ATN biomarkers. Thirty-two thoracic vascular surgical patients were recruited into a prospective biomarker cohort study with assessment of delirium severity and incidence (NCT02926417). CSF (n = 54) and plasma (n = 118) samples were sent for biomarker analysis for tTau, phosphorylated tau-181 (pTau) (plasma n = 53), NfL, and amyloid-β 42/40 ratio (Ab42/40-ratio). The primary outcome was the correlation of preoperative to postoperative change in ATN biomarkers with the highest postoperative Delirium Rating Scale-98 score. CSF and plasma biomarkers all increased postoperatively (all p < .05, n = 13 paired preoperative–postoperative samples). Delirium severity was associated with peak changes in CSF tTau (p = .007, r = .710) and pTau (p = .01, r = .667) but not NfL (p = .09, ρ = .491) or Ab42/40-ratio (p = .18, ρ = .394). Sensitivity analysis with exclusion of participants with putative spinal cord ischemia shifted the NfL result to significance (p < .001, ρ = .847). Our data show that changes in tau and biomarkers of neurodegeneration in the CSF are associated with delirium severity. These data should be considered hypothesis-generating and future studies should identify if these changes are robust to confounding.

Contains fulltext : 194255.pdf (Publisher’s version ) (Open Access) BACKGROUND: Emphysema has considerable variability in its regional distribution. Craniocaudal emphysema distribution is an important predictor of the response to lung volume reduction. However, there is little consensus regarding how to define upper lobe-predominant and lower lobe-predominant emphysema subtypes. Consequently, the clinical and genetic associations with these subtypes are poorly characterized. METHODS: We sought to identify subgroups characterized by upper-lobe or lower-lobe emphysema predominance and comparable amounts of total emphysema by analyzing data from 9,210 smokers without alpha-1-antitrypsin deficiency in the Genetic Epidemiology of COPD (COPDGene) cohort. CT densitometric emphysema was measured in each lung lobe. Random forest clustering was applied to lobar emphysema variables after regressing out the effects of total emphysema. Clusters were tested for association with clinical and imaging outcomes at baseline and at 5-year follow-up. Their associations with genetic variants were also compared. RESULTS: Three clusters were identified: minimal emphysema (n = 1,312), upper lobe-predominant emphysema (n = 905), and lower lobe-predominant emphysema (n = 796). Despite a similar amount of total emphysema, the lower-lobe group had more severe airflow obstruction at baseline and higher rates of metabolic syndrome compared with subjects with upper-lobe predominance. The group with upper-lobe predominance had greater 5-year progression of emphysema, gas trapping, and dyspnea. Differential associations with known COPD genetic risk variants were noted. CONCLUSIONS: Subgroups of smokers defined by upper-lobe or lower-lobe emphysema predominance exhibit different functional and radiological disease progression rates, and the upper-lobe predominant subtype shows evidence of association with known COPD genetic risk variants. These subgroups may be useful in the development of personalized treatments for COPD.

The use of antidepressants in pregnant women is rising, with rates up to 7.5% in the United States. Selective serotonin reuptake inhibitors (SSRIs) are currently the most common antidepressant prescribed to pregnant women. The teratogenic effects of SSRI exposure are debated because of discrepancies in epidemiological studies. As an alternative to epidemiological and animal studies, human embryonic stem cell research (hESC) provides a human-based experimental model to examine the risks of prenatal SSRI exposure. Neural crest stem cells (NCSCs) play an important role in craniofacial and cardiac development as precursors to craniofacial bones and heart septa. This study examines the effects of paroxetine (Paxil) and sertraline (Zoloft) exposure on proliferation, migration, and AP-2α protein expression of NCSC in vitro. hESCs were exposed to paroxetine and sertraline at three concentrations while undergoing directed differentiation into NCSCs. Our results indicate exposure to paroxetine significantly increased proliferation, migration, and AP-2α protein expression in NCSCs. Exposure to sertraline significantly decreased proliferation and significantly increased AP-2α protein expression in NCSC. This evidence suggests paroxetine and sertraline alter normal NCSC behavior and may thereby disrupt cardiac and craniofacial development.

Quantify associations of human milk feeding with in-hospital growth and examine differences by human milk type (maternal or donor).We included infants born33 weeks' gestation and1500 g from 9 Neonatal Intensive Care Units (n = 1429). We estimated associations of percent of visit days fed any human milk (maternal or donor) and percent of days fed donor milk with weight, length, and head z-scores at discharge or transfer using a linear mixed model, adjusting for birth size and other covariates.Any human milk feeding was not associated with growth outcomes. Infants fed donor milk on ≥50% of days had less favorable growth vs. those fed50% [z-scores-weight: -1.1 vs. -0.7 (p = 0.04); length: -1.5 vs. -1.1 (p = 0.04); head -1.0 vs. -0.3 (p 0.01)].Fortified human milk was not associated with impaired growth compared with preterm formula.

Electroencephalography signatures of amyloid-β, tau and neurodegenerative pathologies would aid in screening for, tracking progression of, and critically, understanding the pathogenesis of dementia. We hypothesized that slowing of the alpha peak frequency, as a signature of hyperpolarization-activated cyclic nucleotide gated ‘pacemaker’ channel activity, would correlate with amyloid and tau pathology burden measured by amyloid (Pittsburgh Compound B) and tau (MK-6240) positron emission tomography or CSF biomarkers. We also hypothesized that EEG power would be associated with neurodegeneration (CSF neurofilament light and hippocampal volume). Wakeful high-density EEG data were collected from 53 subjects. Both amyloid-β and tau pathology were associated with slowing in the alpha peak frequency [Pittsburgh Compound B (+) vs. Pittsburgh Compound B (−) subjects, P = 0.039 and MK-6240 (+) vs. MK-6240 (−) subjects, P = 0.019]. Furthermore, slowing in the peak alpha frequency correlated with CSF Aβ42/40 ratio (r2 = 0.270; P = 0.003), phosphoTau (pTau181, r2 = 0.290; P = 0.001) and pTau181/Aβ42 (r2 = 0.343; P, EEG signatures of amyloid-β, tau, and neurodegenerative pathologies would aid in the understanding the pathogenesis of dementia. Both amyloid-β and tau pathology were associated with slowing in the alpha peak frequency while neurodegeneration was associated with lower EEG power., Graphical Abstract Graphical Abstract

OBJECTIVES Celiac disease (CeD) has been associated with increased mental health disorders (MHD) and psychosocial distress in children, which may complicate treatment with the gluten-free diet (GFD). This single-center cross-sectional study examined psychological comorbidities in children with CeD to assess psychological needs in CeD care. METHODS Participants were 73 parents (95% mothers) of children (ages 3-18) attending a multidisciplinary celiac disease clinic. Parents completed electronic surveys about their child's MHD history, psychological symptoms, and GFD experiences. Rates of MHD were calculated and compared with National Institute of Mental Health population-level data. Differences in psychosocial symptoms and GFD experiences were examined based on child age, time since CeD diagnosis, and MHD. RESULTS Thirty-four percentage of children had at least 1 MHD; anxiety disorders (16%, P

The effects of prenatal exposure to Polychlorinated biphenyls (PCBs) on the development of asthma, frequent ear infections, and eczema/hay fever are not well understood. We aim to investigate associations between prenatal PCB exposure and these health outcomes in the offspring of women who worked at the LaSalle Electrical Utilities Company (EUC).A retrospective cohort with at least one live birth and known employment time at EUC was eligible for this analysis. Exposure was defined and categorized by the number of fiscal quarters worked during the PCB era (1952-1981). A total of 288 women with 800 live births were included. A Chi-Square test was used to compare maternal and child characteristics across exposure groups and repeated measures logistic regression, controlling for clustering among siblings, was used to assess the associations between prenatal PCB exposure and these outcomes.After adjustment for confounding and independent maternal predictors, 1-4 quarters of prenatal exposure to PCBs increased the odds for asthma (OR 3.24[1.30-8.09]), eczema/hay fever (OR 3.29[1.54-7.04]), and frequent ear infections (OR 2.24[1.19-4.22]) when compared with persons unexposed/exposed only to naphthalenes. The significance of the associations varied by exposure period and level of exposure, with the strongest associations in those employed exclusively after 1952 when PCBs were introduced.These results support previous findings of associations of prenatal exposure to PCBs with asthma, eczema/hay fever, and frequent ear infections. Additional prospective studies are needed to confirm these findings. Also required are more precise PCB exposures to separate them from other exposures in occupational settings.

The heritability of chronic obstructive pulmonary disease (COPD) cannot be fully explained by recognized genetic risk factors identified as achieving genome-wide significance. In addition, the combined contribution of genetic variation to COPD risk has not been fully explored. We sought to determine: (1) whether studies of variants from previous studies of COPD or lung function in a larger sample could identify additional associated variants, particularly for severe COPD; and (2) the impact of genetic risk scores on COPD. We genotyped 3,346 single-nucleotide polymorphisms (SNPs) in 2,588 cases (1,803 severe COPD) and 1,782 control subjects from four cohorts, and performed association testing with COPD, combining these results with existing genotyping data from 6,633 cases (3,497 severe COPD) and 5,704 control subjects. In addition, we developed genetic risk scores from SNPs associated with lung function and COPD and tested their discriminatory power for COPD-related measures. We identified significant associations between SNPs near PPIC (P = 1.28 X 10(-8)) and PPP4R4/SERPINA1 (P = 1.01 X 10(-8)) and severe COPD; the latter association may be driven by recognized variants in SERPINA1. Genetic risk scores based on SNPs previously associated with COPD and lung function had a modest ability to discriminate COPD (area under the curve, similar to 0.6), and accounted for a mean 0.9-1.9% lower forced expiratory volume in 1 second percent predicted for each additional risk allele. In a large genetic association analysis, we identified associations with severe COPD near PPIC and SERPINA1. A risk score based on combining genetic variants had modest, but significant, effects on risk of COPD and lung function.

This thesis is concerned with the chemical modification of polymers in the preparation of a library of materials which exhibit altered surface properties as a result of the surface chemical functionality, with particular emphasis on the development of materials that control biofouling and are antibacterial. Chemical modification of crosslinked polystyrene, in film and microsphere form, was carried out by carbene insertion followed by diazonium coupling. This provided access to a collection of materials with varying surface chemistry, whilst the bulk properties of the polystyrene substrates were maintained. Synthesis of the diaryldiazo and the diazonium salts used to perform the surface modifications is described, as well as the preparation and characterisation of the materials.Analysis of the ability of the materials to adsorb and bind the protein bovine serum albumin (BSA) is presented with data obtained from two methods of observation. Quartz Crystal Microbalance with Dissipation (QCM-D) and a protein assay based on the change in optical density of a BSA/PBS solution are used to demonstrate how the specific surface chemistry of the materials influences the ability to adsorb and bind protein. The behaviour of the materials was time dependent and was rationalised with respect to the surface water contact angle and the calculated parameters polar surface area and % polar surface area of the functional groups added to the surfaces.Finally, penicillin loaded materials were prepared and their antibacterial activity was tested against E. coli and S. aureus, demonstrating that the antibiotic is still active from within the polystyrene scaffold.

Context: The pediatric intensive care unit (PICU) of Stony Brook University Hospital (Stony Brook, NY, USA) developed a family advocacy board to assist staff in providing patientand family-centered care. The PICU Family Advocacy Board works in partnership with the medical center’s leadership to promote and enhance family-centered pediatric care and services. The advocacy board is founded on the understanding that families play a vital role in ensuring the health and well-being of children. Methods: Using the “Are Families Considered Visitors in Our Hospital or Unit?” self-assessment developed by the Institute for Family-Centered Care, we asked pediatric critical care staff to assess how well family presence and participation is supported on the unit. The data obtained from the assessment was used to help determine priorities for the advocacy board. Results: The greatest improvement in the postimplementation assessment concerned questions related to patients and families as advisors. Answers for four questions in this category showed a statistically significant improvement (p ≤ 0.0001) in the postimplementation data in comparison with the preimplementation data. Staff perception of the level of family involvement during anesthesia induction and after induction increased from 42% before implementation to 78% after implementation (p = 0.0343). The perception of inclusion of family members during resuscitation increased from 28% before implementation to 90% after implementation (p ≤ 0.0001). Conclusions: Patients’ family members and unit staff have responded positively to the development of the parent advisory board and the deployment of board members’ recommendations. Family members bring valuable experience and insight into the development of unit processes. Patients’ and family members’ ideas and participation in decision making should be embraced, not feared.

Background Pulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed a genome-wide association study (GWAS) in 9919 current and former smokers in the COPDGene study (6659 non-Hispanic Whites [NHW] and 3260 African Americans [AA]) to identify associations with spirometric measures (post-bronchodilator FEV1 and FEV1/FVC). We also conducted meta-analysis of FEV1 and FEV1/FVC GWAS in the COPDGene, ECLIPSE, and GenKOLS cohorts (total n = 13,532). Results Among NHW in the COPDGene cohort, both measures of pulmonary function were significantly associated with SNPs at the 15q25 locus [containing CHRNA3/5, AGPHD1, IREB2, CHRNB4] (lowest p-value = 2.17 × 10−11), and FEV1/FVC was associated with a genomic region on chromosome 4 [upstream of HHIP] (lowest p-value = 5.94 × 10−10); both regions have been previously associated with COPD. For the meta-analysis, in addition to confirming associations to the regions near CHRNA3/5 and HHIP, genome-wide significant associations were identified for FEV1 on chromosome 1 [TGFB2] (p-value = 8.99 × 10−9), 9 [DBH] (p-value = 9.69 × 10−9) and 19 [CYP2A6/7] (p-value = 3.49 × 10−8) and for FEV1/FVC on chromosome 1 [TGFB2] (p-value = 8.99 × 10−9), 4 [FAM13A] (p-value = 3.88 × 10−12), 11 [MMP3/12] (p-value = 3.29 × 10−10) and 14 [RIN3] (p-value = 5.64 × 10−9). Conclusions In a large genome-wide association study of lung function in smokers, we found genome-wide significant associations at several previously described loci with lung function or COPD. We additionally identified a novel genome-wide significant locus with FEV1 on chromosome 9 [DBH] in a meta-analysis of three study populations. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0299-4) contains supplementary material, which is available to authorized users.

The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts.Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK.Statistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively.Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate.

We sought to determine what adults in an inner-city setting know about the specific effects of adult cigarette smoking on child health. A cross-sectional survey was conducted at an inner-city community health center in the Bronx, New York; 684 subjects participated. Overall, 21% were current smokers, 19% had quit, and 60% had never smoked. While the majority of subjects knew about the effects of smoking on adult health, they were unaware of the extent to which smoking was harmful to child health. Notably, 72% did not know that cigarette smoking increased the risk for ear infections in children, 68% did not know that smoking increased the risk of colds in children, and 61% did not know that smoking increased the risk of sudden infant death syndrome. The findings suggest a need for public health education about the effects of adult smoking on child health.

Background: There are limited data on the impact of feedback of incidental findings (IFs) from research imaging. We evaluated the impact of UK Biobank’s protocol for handling potentially serious IFs in a multi-modal imaging study of 100,000 participants (radiographer ‘flagging’ with radiologist confirmation of potentially serious IFs) compared with systematic radiologist review of all images. Methods: Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry scans from the first 1000 imaged UK Biobank participants were independently assessed for potentially serious IFs using both protocols. We surveyed participants with potentially serious IFs and their GPs up to six months after imaging to determine subsequent clinical assessments, final diagnoses, emotional, financial and work or activity impacts. Results: Compared to systematic radiologist review, radiographer flagging resulted in substantially fewer participants with potentially serious IFs (179/1000 [17.9%] versus 18/1000 [1.8%]) and a higher proportion with serious final diagnoses (21/179 [11.7%] versus 5/18 [27.8%]). Radiographer flagging missed 16/21 serious final diagnoses (i.e., false negatives), while systematic radiologist review generated large numbers of non-serious final diagnoses (158/179) (i.e., false positives). Almost all (90%) participants had further clinical assessment (including invasive procedures in similar numbers with serious and non-serious final diagnoses [11 and 12 respectively]), with additional impact on emotional wellbeing (16.9%), finances (8.9%), and work or activities (5.6%). Conclusions: Compared with systematic radiologist review, radiographer flagging missed some serious diagnoses, but avoided adverse impacts for many participants with non-serious diagnoses. While systematic radiologist review may benefit some participants, UK Biobank’s responsibility to avoid both unnecessary harm to larger numbers of participants and burdening of publicly-funded health services suggests that radiographer flagging is a justifiable approach in the UK Biobank imaging study. The potential scale of non-serious final diagnoses raises questions relating to handling IFs in other settings, such as commercial and public health screening.

OBJECTIVES Oesophageal pH monitoring is the gold standard technique for the detection of gastro-oesophageal reflux in adults and children. A standard parameter used to define “abnormal” reflux is the percentage of recording time for which the gastric pH is METHODS Simultaneous oesophageal and gastric pH monitoring was carried out on all infants who were milk fed exclusively and admitted to hospital for suspected gastro-oesophageal reflux. In vitro studies were performed to establish the buffering capacities of the fruit juice, Dioralyte (a glucose electrolyte solution), breast milk, and milk formula feeds available on the paediatric wards. RESULTS Complete sets of data were obtained from 30 babies with a mean age of 4 months. Gastric pH was ⩽ 4 for a mean (SEM) of 42.4 (4.9)% of the recording time. The mean (SEM) percentage time that oesophageal pH was 4 increased this value to 17.81 (2.46)%. Using a cut off point of 10%, 11 of the 30 babies would have been diagnosed positive for reflux using the conventional method; however, recalculation by ignoring the time for which gastric pH was high doubled this to 22 positive for reflux. CONCLUSION Combined oesophageal and gastric pH monitoring greatly increases the number of positive results from tests in infants on regular milk feeds. Key messages Reflux of neutral feeds is not easily detectable by conventional pH monitoring procedures Conventional pH monitoring may severely underestimate the incidence of gastro-oesophageal reflux in babies A dual probe approach, which monitors gastric acid and oesophageal pH, leads to a significantly higher diagnosis rate

Significant refractive errors are common among older children and adults with Down syndrome. We examined infants and children with Down syndrome to determine the prevalence of these errors at younger ages. Noncycloplegic retinoscopy was used to determine the refractive state of 92 infants and children with Down syndrome, aged 4 months to 12 years. The results for infants show a similar distribution of refractive errors in patients with Down syndrome and an age-matched control group. However, rather than a narrower distribution for the older age groups, as is the case with the controls, the distribution is wider, and the prevalence of refractive errors (including astigmatism) is higher among young children with Down syndrome than among controls. This high prevalence of refractive defects cannot be explained by the presence of strabismus or other pathologies.

Crista Chemical Company LLC’s (3C) goal was to develop a novel, low-cost, industrial method of plating titanium on metallic and nonmetallic materials. Crista Chemical Company achieved this goal by developing an innovative technology of titanium electroplating and receiving a patent for the achievement U.S. Patent No. 9,023,187, and soon to be published ASTM B999-15. The innovation was ground breaking as before the discovery, titanium electroplating was considered impossible. Crista Chemical Company’s revolutionary innovation electrodeposits coatings of Titanium and Titanium-zirconium alloys on conductive and non-conductive substrates coated with low, medium, or high phosphate electroless nickel. Two methods of titanium deposition were designed and optimized. One was a conventional electroplating method—which used constant current—and another one was a nanocrystalline electrodeposition (we refer to as the “turbo method”), which uses pulse plating. In both methods electrodeposition of the titanium alloys proceeded from the sulfuric acid solution. The advantages of the method of plating titanium include a) low cost, b) relatively low number of process steps, thus posing minimal effect on the environment (safer and zero discharge process) and c) very broad application. Moreover, Produced materials are characterized by a) light weight, b) high corrosion resistance c) high yield strength, d) wear resistance, e) high resilience, stiffness at room temperature as well as at elevated temperature (e.g. up to 200C). This makes the titanium coating an attractive technology for a variety of industries including: high efficiency batteries, medical applications, biotechnology, aerospace, defense, sports and automotive.

Elevated pre-pregnancy BMI, excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM) are known determinants of fetal growth. The role of placental weight is unclear. We aimed to examine the extent to which placental weight mediates the associations of pre-pregnancy BMI, GWG, and GDM with birth weight-for-gestational age, and whether the relationships differ by preterm status.We examined 1,035 mother-infant pairs at birth from the Boston Birth Cohort. Data were collected by questionnaire and clinical measures. Placentas were weighed without membranes or umbilical cords. We performed sequential models excluding and including placental weight, stratified by preterm status.We found that 21% of mothers were obese, 42% had excessive GWG, and 5% had GDM. Forty-one percent were preterm. Among term births, after adjustment for sex, gestational age, maternal age, race, parity, education, smoking, and stress during pregnancy, birth weight-for-gestational age z-score was 0.55 (0.30, 0.80) units higher for pre-pregnancy obesity vs. normal weight. It was 0.34 (0.13, 0.55) higher for excessive vs. adequate GWG, 0.67 (0.24, 1.10) for GDM vs. no DM, with additional adjustment for pre-pregnancy BMI. Adding placental weight to the models attenuated the estimates for pre-pregnancy obesity by 20%, excessive GWG by 32%, and GDM by 21%. Among preterm infants, GDM was associated with 0.67 (0.34, 1.00) higher birth weight-for-gestational age z-score, but pre-pregnancy obesity and excessive GWG were not. Attenuation by placental weight was 36% for GDM.These results suggest that placental weight partially mediates the effects of pre-pregnancy obesity, GDM, and excessive GWG on fetal growth among term infants.

The relationship between normal body temperature, end-expired breath temperature, and blood alcohol concentration (BAC)/breath alcohol concentration (BrAC) ratio was studied in 98 subjects (84 men, 14 women). Subjects consumed alcohol sufficient to produce a BrAC of at least 0.06 g/210 L 45-75 min after drinking. Breath samples were analyzed using an Intoxilyzer 8000 specially equipped to measure breath temperature. Venous blood samples and body temperatures were then taken. The mean body temperature of the men (36.6 degrees C) was lower than the women (37.0 degrees C); however, their mean breath temperatures were virtually identical (men: 34.5 degrees C; women: 34.6 degrees C). The BAC exceeded the BrAC for every subject. BAC/BrAC ratios were calculated from the BAC and BrAC analytical results. There was no difference in the BAC/BrAC ratios for men (1:2379) and women (1:2385). The correlation between BAC and BrAC was high (r = 0.938, p < 0.0001), whereas the correlations between body temperature and end-expired breath temperature, body temperature and BAC/BrAC ratio, and breath temperature and BAC/BrAC ratio were much lower. Neither normal body temperature nor end-expired breath temperature was strongly associated with BAC/BrAC ratio.