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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.
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.
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.
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.
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.
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.
Semiconductor nitrides grown on substrates with a large lattice mismatch typically contain extended and point defects that prevent the full potential of this material system from being attained. Among allthe substrate options explored so far, freestanding GaN templates appear ideal for homoepitaxial growth of GaN films. To this end, hydride vapor-phase epitaxial (HVPE) grown GaN templates with a thickness of more than 200 μm were thermally lifted off from the sapphire substrate and mechanically polished. The defect densityof such a template is expected to be non-uniform in the growth direction, especially near the back surface which was in close vicinity of the sapphire substrate. We, therefore, studied the transport properties of this template before and after the removal of a 30 μm region from the back-side. For as-prepared GaN, Hall mobilities of 1100 cm2/V-s and 6800 cm2/V-s were obtained at 295 K and 50 K, respectively. A simultaneous fitting of mobility and carrier concentration was used to quantify the contribution ofdifferent scattering mechanisms. When the backside was etched by ∼30 μm, Hall mobilities improved to 1200 cm2/V-s at 295 K and 7385 cmsup2/V-s at 48 K, respectively. A numerical solution of the Boltzmann transport equation (BTE) that deals with the inelastic nature of electron scattering by polar optical mode was employed to determine the acceptor concentration. Raman spectroscopy was employed to obtain LO and TO phonon energies, which were then used in the above-mentioned calculations. The best fittings of the mobility and carrier concentration data yield an average acceptor concentration of 4.9×1015 cm-3 and a donor concentration of 2.1×1016 cm-3 for the as-prepared GaN. The average acceptor concentration decreased to 2.4×1015 cm-3 after etching of the backside, which confirms that the etched-away region contained higher density of defects. The donor activation energy is derived to be 25.2 meV. Our analysis demonstrated high quality of the freestanding GaN substrate with the highest reported electron mobility for wurtzite GaN.
High tensile stresses develop in passivated aluminum line metallizations on silicon substrates after excursion to elevated temperatures. The principal mechanisms to relax these stresses at room temperature are plastic deformation and grain boundary void growth. It is shown that stress relaxation and void growth are intimately connected.
Using void-related compensation in Al-implanted GaAs, high-resistivity isolation regions that are thermally stable to high temperatures (> 700 °C) are demonstrated. The high-temperature thermal stability of the isolation regions allows the simplification of device processing in which a single high-temperature anneal (e.g., at 900 °C) can be used to activate the implant dopants in the device-active regions, and simultaneously to convert the Al-implanted regions highly resistive for electrical isolation. Other advantages of using void-related isolation will also be discussed.
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.
We have studied the spectrum of various types of a-SiGe:H alloys for pin and Schottky barrier photodlodes, in which the band gaps of the a-SiGe:H vary between 1.75 eV and 1.35 eV. It has been found that the spectral re-ponse of the Schottky barrier diode shifts significantly to longer wavelength and the quantum efficiency decreases with an increase in i layer thickness. However, for the pin diode, an increase in the i layer thickness can hardly shift the spectrum to longer wavelength. For both pin and Schottky barrier diodes, the quantum efficiency can be increased by increasing the reverse bias. Therefore, an enhanced spectrum with a maximum at 800nm and a tail to lun can be achieved for a reverse-biased a-SiGe:H Schottky barrier diode. The results indicate that a-SiGe:H has a great potential for a low cost infrared photodetector.