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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.
To evaluate the clinical impact of an antimicrobial stewardship program (ASP) on high-risk pediatric patients.
Retrospective cohort study.
Free-standing pediatric hospital.
This study included patients who received an ASP review between March 3, 2008, and March 2, 2017, and were considered high-risk, including patients receiving care by the neonatal intensive care (NICU), hematology/oncology (H/O), or pediatric intensive care (PICU) medical teams.
The ASP recommendations included stopping antibiotics; modifying antibiotic type, dose, or duration; or obtaining an infectious diseases consultation. The outcomes evaluated in all high-risk patients with ASP recommendations were (1) hospital-acquired Clostridium difficile infection, (2) mortality, and (3) 30-day readmission. Subanalyses were conducted to evaluate hospital length of stay (LOS) and tracheitis treatment failure. Multivariable generalized linear models were performed to examine the relationship between ASP recommendations and each outcome after adjusting for clinical service and indication for treatment.
The ASP made 2,088 recommendations, and 50% of these recommendations were to stop antibiotics. Recommendation agreement occurred in 70% of these cases. Agreement with an ASP recommendation was not associated with higher odds of mortality or hospital readmission. Patients with a single ASP review and agreed upon recommendation had a shorter median LOS (10.2 days vs 13.2 days; P < .05). The ASP recommendations were not associated with high rates of tracheitis treatment failure.
ASP recommendations do not result in worse clinical outcomes among high-risk pediatric patients. Most ASP recommendations are to stop or to narrow antimicrobial therapy. Further work is needed to enhance stewardship efforts in high-risk pediatric patients.
Patients with cardiovascular diseases are common in the emergency department (ED), and continuity of care following that visit is needed to ensure that they receive evidence-based diagnostic tests and therapy. We examined the frequency of follow-up care after discharge from an ED with a new diagnosis of one of three cardiovascular diseases.
We performed a retrospective cohort study of patients with a new diagnosis of heart failure, atrial fibrillation, or hypertension, who were discharged from 157 non-pediatric EDs in Ontario, Canada, between April 2007 and March 2014. We determined the frequency of follow-up care with a family physician, cardiologist, or internist within seven and 30 days, and assessed the association of patient, emergency physician, and family physician characteristics with obtaining follow-up care using cause-specific hazard modeling.
There were 41,485 qualifying ED visits. Just under half (47.0%) had follow-up care within seven days, with 78.7% seen by 30 days. Patients with serious comorbidities (renal failure, dementia, COPD, stroke, coronary artery disease, and cancer) had a lower adjusted hazard of obtaining 7-day follow-up care (HRs 0.77-0.95) and 30-day follow-up care (HR 0.76-0.95). The only emergency physician characteristic associated with follow-up care was 5-year emergency medicine specialty training (HR 1.11). Compared to those whose family physician was remunerated via a primarily fee-for-service model, patients were less likely to obtain 7-day follow-up care if their family physician was remunerated via three types of capitation models (HR 0.72, 0.81, 0.85) or via traditional fee-for-service (HR 0.91). Findings were similar for 30-day follow-up care.
Only half of patients discharged from an ED with a new diagnosis of atrial fibrillation, heart failure, and hypertension were seen within a week of being discharged. Patients with significant comorbidities were less likely to obtain follow-up care, as were those with a family physician who was remunerated via primarily capitation methods.
The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.
OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.
EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).
Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.
The high prevalence of mild cognitive impairment (MCI) in Hong Kong, as previously reported, requires verification. Furthermore, the relationship between loneliness, depression, and cognitive impairment with regards to MCI are unclear. The present study aims to establish the prevalence of MCI in a community sample in Hong Kong and determine if participants with MCI feel significantly lonelier, even after depression has been taken into consideration.
Participants from a community sample (N = 376) were assessed with subjective and objective measures of cognitive impairments to determine whether the criteria had been met for MCI. The MCI cases are then compared with age, sex, and education-matched controls on subjective measures of loneliness and depression.
A total of 66 (17.6%) participants were diagnosed with MCI. These participants reported significantly higher levels of perceived loneliness and depression compared to the matched controls. Differences between groups in loneliness remained significant, even after depression levels have been controlled.
Loneliness is implicated in MCI. The relationship between loneliness and MCI is, at least, partially independent of depression. The implications of these finding are discussed.
This study aimed to characterise the geometry of the human bilateral spiral cochlea by measuring curvature and length.
Eight subjects were recruited in this study. Magnetic resonance imaging was used to visualise the right and left cochlea. Visualisation of the cochlear spiral was enhanced by T2 weighting and further processing of the raw images. The spirals were divided into three segments: the basal turn, the middle turn and the apex turn. The length and curvature of each segment were non-invasively measured.
The mean left and right cochlear lengths were 3.11 cm and 3.95 cm, respectively. The measured lengths of the cochlear spiral are consistent with data in the literature derived from anatomical dissections. Overall, the apex turn segment of the cochlea had the greatest degree of curvature (p < 0.05). The mean apex turn segment curvatures for left and right cochleae were 9.65 cm−1 and 10.09 cm−1, respectively.
A detailed description of the cochlear spiral is provided, using measurements of curvature and length. These data will provide a valuable reference in the development of cochlear implantation procedures for minimising the potential damage during implantation.
The number of pediatric antimicrobial stewardship programs (ASPs) is increasing and program evaluation is a key component to improve efficiency and enhance stewardship strategies.
To determine the antimicrobials and diagnoses most strongly associated with a recommendation provided by a well-established pediatric ASP.
DESIGN AND SETTING
Retrospective cohort study from March 3, 2008, to March 2, 2013, of all ASP reviews performed at a free-standing pediatric hospital.
ASP recommendations were classified as follows: stop therapy, modify therapy, optimize therapy, or consult infectious diseases. A multinomial distribution model to determine the probability of each ASP recommendation category was performed on the basis of the specific antimicrobial agent or disease category. A logistic model was used to determine the odds of recommendation disagreement by the prescribing clinician.
The ASP made 2,317 recommendations: stop therapy (45%), modify therapy (26%), optimize therapy (19%), or consult infectious diseases (10%). Third-generation cephalosporins (0.20) were the antimicrobials with the highest predictive probability of an ASP recommendation whereas linezolid (0.05) had the lowest probability. Community-acquired pneumonia (0.26) was the diagnosis with the highest predictive probability of an ASP recommendation whereas fever/neutropenia (0.04) had the lowest probability. Disagreement with ASP recommendations by the prescribing clinician occurred 22% of the time, most commonly involving community-acquired pneumonia and ear/nose/throat infections.
Evaluation of our pediatric ASP identified specific clinical diagnoses and antimicrobials associated with an increased likelihood of an ASP recommendation. Focused interventions targeting these high-yield areas may result in increased program efficiency and efficacy.
Over the past decade, large outbreaks of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have occurred in correctional facilities across the country. Although many have been managed with aggressive interventions, response to standard infection control procedures has been variable, highlighting our incomplete understanding of staphylococcal transmission in this setting. Environmental contamination has recently emerged as a possible target for novel prevention and control strategies. This study sought to characterize the relationship between environmental contamination and clinical infection in this vulnerable population.
We conducted a case-control study of S. aureus environmental contamination at 2 New York State (NYS) maximum security prisons: Sing Sing (men) and Bedford Hills (women).
We report a rare case of concurrent myeloid sarcoma and acute fulminant invasive fungal sinusitis in a patient with relapsed acute myeloid leukaemia.
A 73-year-old man was diagnosed with acute myeloid leukaemia and developed relapse one year later. After two courses of azacytidine, he began suffering from a dull pain in the left temporal and orbital regions. Sinus computed tomography showed a localised lesion in the left ethmoid sinus, which rapidly progressed to an extensive intracranial mass within one month. Surgical debridement was performed, and histopathological analysis revealed the coexistence of myeloid sarcoma and acute fulminant invasive fungal sinusitis. The patient responded well to prompt surgical debridement, antifungal medication and radiotherapy.
Coexistence of sinonasal myeloid sarcoma and acute fulminant invasive fungal sinusitis poses an urgent diagnostic and management challenge to clinicians. Timely recognition of this rare comorbid condition is warranted as application of appropriate treatment can save lives.
The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.
Dye type solar cells, especially those incorporating low cost dyes suffer from a very narrow photo-response wavelength range. Motivated by natural photosynthesis research, energy relay dyes (ERDs) appear to offer a possibility to broaden the dye-cell spectral response. In-turn photovoltaic cells can be an extremely sensitive tool for investigation of dye ERD photochemistry. Sensitive Chlorophyll based dye-type solar cells were prepared from purified natural Chlorophyll A. The importance of Chlorophyll purity is discussed as well as the use of purified Chlorophyll A in combination with ERD’s. . Results shed light on many interesting phenomenon including the nature of purified Chlorophyll A excitation and absorption. Importantly, it was found by this work that the ERD architecture when combined with a photosensitizer do not appear to having greater absorption in the infrared region of the spectrum than the ERD alone indicating a lack of cooperative absorption.
Previous studies with nonhuman species have shown that animals exposed to early adversity show differential DNA methylation relative to comparison animals. The current study examined differential methylation among 14 children raised since birth in institutional care and 14 comparison children raised by their biological parents. Blood samples were taken from children in middle childhood. Analysis of whole-genome methylation patterns was performed using the Infinium HumanMethylation27 BeadChip assay (Illumina), which contains 27,578 CpG sites, covering approximately 14,000 gene promoters. Group differences were registered, which were characterized primarily by greater methylation in the institutionalized group relative to the comparison group, with most of these differences in genes involved in the control of immune response and cellular signaling systems, including a number of crucial players important for neural communication and brain development and functioning. The findings suggest that patterns of differential methylation seen in nonhuman species with altered maternal care are also characteristic of children who experience early maternal separation.
To investigate the association between cooking behaviour and long-term survival among elderly Taiwanese.
Cohort study. The duration of follow-up was the interval between the date of interview and the date of death or 31 December 2008, when censored for survivors. Information used included demographics, socio-economic status, health behaviours, cooking frequencies, physical function, cognitive function, nutrition knowledge awareness, eating out habits and food and nutrient intakes. These data were linked to death records. Cox proportional-hazards models were used to evaluate cooking frequency on death from 1999 to 2008 with related covariate adjustments.
Elderly Nutrition and Health Survey in Taiwan, 1999–2000.
Nationally representative free-living elderly people aged ≥65 years (n 1888).
During a 10-year follow-up, 695 participants died. Those who cooked most frequently were younger, women, unmarried, less educated, non-drinkers of alcohol, non-smokers, without chewing difficulty, had spouse as dinner companion, normal cognition, who walked or shopped more than twice weekly, who ate less meat and more vegetables. Highly frequent cooking (>5 times/week, compared with never) predicted survival (hazard ratio (HR) = 0·47; 95 % CI, 0·36, 0·61); with adjustment for physical function, cognitive function, nutrition knowledge awareness and other covariates, HR was 0·59 (95 % CI, 0·41, 0·86). Women benefited more from cooking more frequently than did men, with decreased HR, 51 % v. 24 %, when most was compared with least. A 2-year delay in the assessment of survivorship led to similar findings.
Cooking behaviour favourably predicts survivorship. Highly frequent cooking may favour women more than men.
To investigate genetic and lifestyle factors and their interactions on plasma homocysteine (Hcy) concentrations in the Boston Puerto Rican population.
Cross-sectional study. Plasma concentrations of Hcy, folate, vitamin B12 and pyridoxal phosphate were measured, and genetic polymorphisms were determined. Data on lifestyle factors were collected in interviews.
A population survey of health and nutritional measures.
A total of 994 Puerto Rican men and women residing in the Boston metropolitan area.
Smoking status was positively associated with plasma Hcy. Genetic polymorphisms MTHFR 677C→T, FOLH1 1561C→T, FOLH1 rs647370 and PCFT 928A→G interacted significantly with smoking for Hcy. MTHFR 1298A→C (P = 0·040) and PCFT 928A→G (P = 0·002) displayed significant interactions with alcohol intake in determining plasma Hcy. Subjects with PCFT928GG genotype had significantly higher plasma Hcy concentrations compared with carriers of the A allele (AA+AG; P = 0·030) among non-drinking subjects. When consuming alcohol, GG subjects had lower plasma Hcy levels compared with AA+AG subjects. Physical activity interacted significantly with MTR 2756A→G in determining plasma Hcy (P for interaction = 0·002). Smoking interacted with physical activity for plasma Hcy (P for interaction = 0·023).
Smoking and drinking were associated plasma Hcy concentrations. Genetic variants involved in folate metabolism further modify the effects of lifestyle on plasma Hcy.
For the development of cytotoxic anticancer pharmaceuticals, the initial phase 1 clinical trials in patients with advanced cancer disease usually include determining a maximum tolerated dose (MTD) and identifying dose-limiting toxicity (DLT). The MTD is usually defined as the dose tolerated by five out of six patients with acceptable levels of DLT and dose levels above which result in unacceptable DLT in two or more patients. The dose–response curve for many pharmaceuticals in this class is steep. Traditionally, the dose recommended for phase 2 trials of cytotoxic agents is based on the MTD determined in phase 1. The inherent assumption in establishing and using an MTD is that the therapeutic effect and the associated toxicities are correlated and that the mechanism of action of both the toxic and therapeutic effects is the same – higher doses result in greater efficacy. Therefore, it is not uncommon for the efficacious dose of anticancer pharmaceuticals to be at or near the MTD. Predicting the dose and exposure at which DLT will likely occur in humans provides value in designing and conducting the first clinical trial for a cytotoxic anticancer pharmaceutical.
Before testing in patients, the toxicities of these pharmaceutical candidates are studied in nonclinical species in toxicology studies to determine the DLT. Toxicokinetics (TK) represent the assessment of systemic exposure in toxicity studies, in which pharmacokinetic data are generated, either from the same animals used in the main toxicology study (usually for larger species such as dogs or monkeys) or from a satellite group (usually for smaller species such as rats or mice) at each dose level used in the main toxicology study.
Three antidot arrays with FeNi alloy thickness of 20, 50 and 100 nm have been patterned using magnetron sputtering followed by the electron-beam lithography and lift-off technique. Ferromagnetic resonance technique was used to study dynamic properties of the antidot arrays. These results were compared with the measurements of continuous films with the same composition and thickness. Two distinct resonant fields have been observed for the bias field aligned with the edges of the square holes. Resonance peaks shifted towards each other and eventually merged when the in-plane bias field was rotated towards diagonal of the squares. This dependence has been explained in terms of magnetostatic energy associated with the square holes. The magnitude of this effect was decreasing for the arrays with the reduced thickness. The perpendicular and lateral quantized standing spin wave modes were detected in the reference films and the antidot arrays due to the perpendicular and lateral dimensional confinements.
Surface plasmon resonance (SPR) biosensors are widely used in sensitive chemical, biological and environmental sensing. Recently, the studies of nano-plasmonics in metallic structures have shown that surface plasmons can also be excited by the metallic nanostructures films which can be used for high-throughput and chip-based SPR type sensing. We developed a class of plasmonic crystal-like structures consisting of a film with arrays of periodic nanoslit geometry. Because the engineered array ensures multiple resonance modes, we use the multispectral analysis to evaluate the refractive index sensing capability. Different from the common method monitoring a single peak shift, the multispectral analysis, observing all the peak shifts and intensity changes in the multiple plasmonic resonances in the spectra, can improve the signal-to-noise ratio of the system and enhance the sensing capabilities. In this investigation, we studied the best condition for the gold nanoslit arrays by testing their ability for refractive index sensing, and a high sensitivity of up to 28586 %T nm/RIU was obtained by multispectral analysis (RIU = refreactive index unit, and T= transmission).
Bulk silicon-germanium (SiGe) alloys and two SiGe thick films (4 and 5 μm) on Si wafers were tested with the electron probe microanalyzer (EPMA) using wavelength dispersive spectrometers (WDS) for heterogeneity and composition for use as reference materials needed by the microelectronics industry. One alloy with a nominal composition of Si0.86Ge0.14 and the two thick films with nominal compositions of Si0.90Ge0.10 and Si0.75Ge0.25 on Si, evaluated for micro- and macroheterogeneity, will make good microanalysis reference materials with an overall expanded heterogeneity uncertainty of 1.1% relative or less for Ge. The bulk Ge composition in the Si0.86Ge0.14 alloy was determined to be 30.228% mass fraction Ge with an expanded uncertainty of the mean of 0.195% mass fraction. The thick films were quantified with WDS-EPMA using both the Si0.86Ge0.14 alloy and element wafers as reference materials. The Ge concentration was determined to be 22.80% mass fraction with an expanded uncertainty of the mean of 0.12% mass fraction for the Si0.90Ge0.10 wafer and 43.66% mass fraction for the Si0.75Ge0.25 wafer with an expanded uncertainty of the mean of 0.25% mass fraction. The two thick SiGe films will be issued as National Institute of Standards and Technology Reference Materials (RM 8905).