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Maternal systemic inflammation during pregnancy may restrict embryo−fetal growth, but the extent of this effect remains poorly established in undernourished populations. In a cohort of 653 maternal−newborn dyads participating in a multi-armed, micronutrient supplementation trial in southern Nepal, we investigated associations between maternal inflammation, assessed by serum α1-acid glycoprotein and C-reactive protein, in the first and third trimesters of pregnancy, and newborn weight, length and head and chest circumferences. Median (IQR) maternal concentrations in α1-acid glycoprotein and C-reactive protein in the first and third trimesters were 0.65 (0.53–0.76) and 0.40 (0.33–0.50) g/l, and 0.56 (0.25–1.54) and 1.07 (0.43–2.32) mg/l, respectively. α1-acid glycoprotein was inversely associated with birth size: weight, length, head circumference and chest circumference were lower by 116 g (P = 2.3 × 10−6), and 0.45 (P = 3.1 × 10−5), 0.18 (P = 0.0191) and 0.48 (P = 1.7 × 10−7) cm, respectively, per 50% increase in α1-acid glycoprotein averaged across both trimesters. Adjustment for maternal age, parity, gestational age, nutritional and socio-economic status and daily micronutrient supplementation failed to alter any association. Serum C-reactive protein concentration was largely unassociated with newborn size. In rural Nepal, birth size was inversely associated with low-grade, chronic inflammation during pregnancy as indicated by serum α1-acid glycoprotein.
Several life-threatening diseases of the kidney have their origins in mutational events that occur during embryonic development. In this study, we investigate the role of the Wolffian duct (WD), the earliest embryonic epithelial progenitor of renal tubules, in the etiology of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is associated with a germline mutation of one of the two Pkd1 alleles. For the disease to occur, a second event that disrupts the expression of the other inherited Pkd1 allele must occur. We postulated that this secondary event can occur in the pronephric WD. Using Cre-Lox recombination, mice with WD-specific deletion of one or both Pkd1 alleles were generated. Homozygous Pkd1-targeted deletion in WD-derived tissues resulted in mice with large cystic kidneys and serologic evidence of renal failure. In contrast, heterozygous deletion of Pkd1 in the WD led to kidneys that were phenotypically indistinguishable from control in the early postnatal period. High-throughput sequencing, however, revealed underlying gene and microRNA (miRNA) changes in these heterozygous mutant kidneys that suggest a strong predisposition toward developing ADPKD. Bioinformatic analysis of this data demonstrated an upregulation of several miRNAs that have been previously associated with PKD; pathway analysis further demonstrated that the differentially expressed genes in the heterozygous mutant kidneys were overrepresented in signaling pathways associated with maintenance and function of the renal tubular epithelium. These results suggest that the WD may be an early epithelial target for the genetic or molecular signals that can lead to cyst formation in ADPKD.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors—arousal and attention—via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.
While much research has focused on crop damage following foliar exposure to auxin herbicides, reports documenting the risk posed by exposure via root uptake of irrigation water are lacking. Herbicide residues circulated in tailwater recovery systems may pose threats of cross-crop impacts to nonresistant cultivars with known sensitivity to auxins. An auxin-susceptible soybean [Glycine max (L.) Merr.] cultivar was grown in a controlled growth chamber environment and exposed to dicamba dissolved in irrigation water applied to the soil surface, simulating furrow irrigation. Five herbicide treatment concentrations, ranging from 0.05 to 5.0 mg L−1 and encompassing estimated field doses of 3.1 to 310g ha−1, were applied to the soil of potted soybean plants at V3/V4 or R1 growth stages. Plant injury (0% to 100%), dry mass, height, number of pods, and number of pod-bearing nodes were measured. Kruskal-Wallis and logistic regression analyses were performed to determine treatment differences and examine dose effects. Yield losses were projected using (1) 14 d after treatment plant injury assessments based on injury–yield relationships described for foliar exposures and (2) pod counts. Dicamba concentration was the main significant factor affecting all growth response metrics, and growth stage was a significant explanatory variable only for the height response metric. A nonlinear response to dicamba dose was observed, with the threshold response dose required to affect 50% of plants being three times greater for 40% crop injury compared with 20% injury. Yield projections derived from plant response to root uptake compared with foliar exposure indicate that soybean may express both magnitude of injury and specific symptomology differently when exposure occurs via root uptake. Drift exposure–based models may be incompatible to predict soybean yield loss when injury results from irrigation. Data are needed to develop correlations for predicting yield losses based on field-scale exposure to dicamba in irrigation water, as well as assessment of real-world concentrations of herbicide residues in tailwater recovery systems.
To determine the factors related to multiple ventilation tube insertions in children with otitis media with effusion.
A retrospective review was performed of 126 ears of 81 children aged less than 12 years who had undergone insertion of a Paparella type 1 ventilation tube for the first time between August 2012 and March 2018.
Mean age at the first operation was 4.0 ± 2.2 years, and the mean duration of otitis media with effusion before the first ventilation tube insertion was 5.4 ± 4.5 months. Among 126 ears, 80 (63.5 per cent) had a single ventilation tube insertion and 46 (36.5 per cent) had multiple insertions. On multivariate logistic regression, tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion were independent predictive factors of multiple ventilation tube insertions.
Tympanic membrane retraction, serous middle-ear discharge, and early recurrence of otitis media with effusion after the first tube extrusion are associated with multiple ventilation tube insertions.
A new ESCA (electron spectroscopy for chemical analysis) instrument has been developed to provide high sensitivity and efficient operation for laboratory analysis of composition and chemical bonding in very thin surface layers of solid samples. High sensitivity is achieved by means of the high-intensity, efficient X-ray source described by Davies and Herglotz at the 1968 Denver X-Ray Conference, in combination with the new electron energy analyzer described by Lee at the 1972 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. A sample chamber designed to provide for rapid introduction and replacement of samples has adequate facilities for various sample treatments and conditioning followed immediafely by ESCA analysis of the sample.
Examples of application are presented, demonstrating the sensitivity and resolution achievable with this instrument. Its usefulness in trace surface analysis is shown and some “chemical shifts” measured by the instrument are compared with those obtained by X-ray spectroscopy.
The use of transdiagnostic mental health treatments in low resource settings has been proposed as a possible aid in scaling up mental health services. Modular, multi-problem transdiagnostic treatments can be used to treat a range of mental health problems and are designed to handle comorbidity. Two randomized controlled trials have been completed on one treatment – the Common Elements Treatment Approach, or CETA – delivered by lay counsellors in Iraq and Thailand. This paper utilizes data from two clinical trials to explore the delivery of CETA by lay providers, examining fidelity and flexibility of element use. Data were collected at every therapy session. Clients completed a short symptom assessment and providers described the clinical elements delivered during sessions. Analyses included descriptive statistics of delivery including selection and sequencing of treatment elements, and the variance in element dose, clustering at the counsellor level, using multi-level models. Results indicate that lay providers in low resource settings (with supervision) demonstrated fidelity to the recommended CETA elements, order and dose, and occasionally added in elements and flexed dosage based on client presentation (i.e. flexibility). This modular approach did not result in significantly longer treatment duration. Our analysis suggests that lay providers were able to learn decision-making processes of CETA based on client presentation and adjust treatment as needed with supervision. As modular multi-problem transdiagnostic treatments continue to be explored in low resource settings, research should continue to focus on ‘unpacking’ lay counsellor delivery of these interventions, decision-making processes, and the level of supervision required.
A 1108.6 m long core was recovered at Site U1457 located on the Indus Fan in the Laxmi Basin of the eastern Arabian Sea during IODP Expedition 355. Shipboard examinations defined five lithologic units (I to V) of the lower Paleocene to Holocene sedimentary sequence. In this study, δ13C values of sedimentary organic matter (SOM) confirm the differentiation of the lithologic units and further divide units III and IV into two subunits (1 and 2). Based on the underlying assumption that the SOM is decided primarily by a mixture of marine and terrestrial origins, δ13CSOM values at Site U1457 provide information on the terrestrial catchment conditions since late Miocene time. Low δ13CSOM values from late Miocene to late Pleistocene times are similar (c. −22.0 ‰) for the most part, reflecting a consistent contribution of terrestrial organic matter from the catchment areas characterized by dominant C3 land plants. Significantly lower δ13CSOM values (c. −24.0 ‰) in Unit III-2 (∼8 to ∼7 Ma) might be due to a greater input of C3 terrestrial organic matter. The increase in δ13CSOM values at ∼7 Ma and the appearance of high δ13CSOM values (c. −18.0 ‰) within Unit III-1 (∼7 to ∼2 Ma) indicate that C4 biomass overwhelmed the terrestrial catchment environment as a result of enhanced terrestrial aridity in the Himalayan foreland. The three-end-member simple mixing model, estimating the relative contributions of SOM from terrestrial C3 and C4 plants and marine phytoplankton, supports our interpretation of the distribution of C3 and C4 land plants in the terrestrial catchment environment.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.
Introduction: Gastroenteritis accounts for 1.7 million emergency department visits by children annually in the United States. We conducted a double-blind trial to determine whether twice daily probiotic administration for 5 days, improves outcomes. Methods: 886 children aged 348 months with gastroenteritis were enrolled in six Canadian pediatric emergency departments. Participants were randomly assigned to twice daily Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052, 4.0 x 109 CFU, in a 95:5 ratio or placebo. Primary outcome was development of moderate-severe disease within 14 days of randomization defined by a Modified Vesikari Scale score 9. Secondary outcomes included duration of diarrhea and vomiting, subsequent physician visits and adverse events. Results: Moderate-severe disease occurred in 108 (26.1%) participants administered probiotics and 102 (24.7%) participants allocated to placebo (OR 1.06; 95%CI: 0.77, 1.46; P=0.72). After adjustment for site, age, and frequency of vomiting and diarrhea, treatment assignment did not predict moderate-severe disease (OR, 1.11, 95%CI, 0.80 to 1.56; P=0.53). In the probiotic versus placebo groups, there were no differences in the median duration of diarrhea [52.5 (18.3, 95.8) vs. 55.5 (20.2, 102.3) hours; P=0.31], vomiting [17.7 (0, 58.6) vs. 18.7 (0, 51.6) hours; P=0.18], physician visits (30.2% vs. 26.6%; OR 1.19; 95% CI0.87. 1.62; P=0.27), or adverse events (32.9% vs. 36.8%; OR 0.83; 95%CI 0.62. 1.11; P=0.21). Conclusion: In children presenting to an emergency department with gastroenteritis, twice daily administration of 4.0 x 109 CFU of a Lactobacillus rhamnosus/helveticus probiotic does not prevent development of moderate-severe disease or improvements in other outcomes measured.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
From a 45ks Chandra observation of V42G Oph we have obtained high-resolution X-ray spectra at moderate signal-to-noise, and a, good quality, uninterrupted lightcurve. The spectra are reasonably fit with a cooling flow model, similar to EX Hya and U Gem. Our analysis of the Chandra and additional X-ray/optical lightcurves reveals a persistent modulation at 4.2 hr from 1988 to 2003, likely the white dwarf spin period indicating an intermediate polar nature for V426 Oph.
In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting <3 hours from stroke onset and achieving ultra-early reperfusion (<45 minutes from CTP) are reported. CTP thresholds that predict follow-up infarction vary based on time to reperfusion: Tmax >20 to 23 seconds and cerebral blood flow <5 to 7 ml/min−1/(100 g)−1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
The process of the magnetic polarity reversal of the Sun has been an important subject in the solar physics. The objective of this study is to investigate how solar global magnetic field change over solar cycle by tracking the migration of open magnetic flux regions. The results show that the open magnetic fluxes migrate from one pole to the other crossing the equator during a solar cycle. The migration rate is approximately 10 m s−1, comparable to meridional flow. The results have been published in Scientific Reports (Huang et al. (2017)).
Solar activity is observed to fluctuate with time, undergoing a wide range of periodicities from minutes up to thousands of years as evinced from proxies based on cosmogenic isotopes. In this work, we apply Multichannel Singular Spectrum Analysis (MSSA), a data-adaptive, multivariate technique that simultaneously exploits the spatial and temporal correlations of the input data to extract common modes of variability to investigate the intermediate quasi-periodicities of the green coronal emission line at 530.3 nm for the period between 1944 and 2008. A preliminary MSSA analysis confirms the presence of significant quasi-biennial oscillations in the data with amplitude varying significantly with time and latitude. On the other hand, a clear North-South asymmetry is observed both in their intensity and period distribution.
A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.
In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.
An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.
CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.