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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.
Oxidative stress is implicated in the etiology of schizophrenia, and the antioxidant defense system may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain, and its correlates with clinical and demographic variables, in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r=-.46, p=.015), and a trend-level positive relationship between GSH and duration of illness (r=.34, p=.076).
Our findings are consistent with a possible compensatory upregulation of the antioxidant defense system with longer duration of illness, and suggests the antioxidant defense system may play a role in schizophrenia.
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.
Antimicrobial stewardship programs typically use days of therapy to assess antimicrobial use. However, this metric does not account for the antimicrobial spectrum of activity. We applied an antibiotic spectrum index to a population of very-low-birth-weight infants to assess its utility to evaluate the impact of antimicrobial stewardship interventions.
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.
We used multivariable analyses to assess whether meeting core elements was associated with antibiotic utilization. Compliance with 7 elements versus not doing so was associated with higher use of broad-spectrum agents for community-acquired infections [days of therapy per 1,000 patient days: 155 (39) vs 133 (29), P = .02] and anti-methicillin-resistant S. aureus agents [days of therapy per 1,000 patient days: 145 (37) vs 124 (30), P = .03].
The aim of this study was to (1) assess the long-term mental and behavioral health outcomes of the Deepwater Horizon Oil Spill of residents in the Gulf Coast and to (2) identify populations that may be particularly vulnerable to future disasters.
The Survey of Trauma, Resilience, and Opportunity in Neighborhoods in the Gulf (STRONG) is a population-representative sample of 2520 coastal residents surveyed in Texas, Louisiana, Alabama, Mississippi, and Florida in 2016. We present prevalence estimates for positive screens of depression, anxiety, and alcohol misuse, as well as receipt of health care services. We examine differences in these outcomes across states, affected occupational groups, and demographic groups.
Resource loss attributed to the spill was associated with positive screens for depression and anxiety. Almost 50% of adults screened positive for depression, anxiety, or alcohol misuse, but less than 20% of these currently access mental health care. Black residents were less likely to have health insurance and a usual source of care but were more likely to have visited the emergency room in the past 12 months.
Surveillance data from STRONG can help policy-makers and other stakeholders develop targeted approaches to foster resilience, particularly among vulnerable populations, and thereby mitigate the effects of future disasters.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
Reflection high-energy electron diffraction (RHEED) is one of the most robust and widespread techniques used for in-situ monitoring during molecular beam epitaxy (MBE) growth. Thus, all MBE systems have an electron gun allowing additional electron-beam stimulated in-situ characterizations. At WVU we are developing two such techniques, spectral analysis of cathodoluminescence (CL) in wide bandgap semiconductors and reflection high-energy electron diffraction-total reflection angle x-ray spectroscopy (RHEED-TRAXS) for in-situ composition monitoring and control.A pressing issue remaining for epitaxial growth is real-time compositional control to a high level of accuracy. For many materials, such as multi-element nitrides and oxides with unity sticking coefficients, it would be extremely beneficial to monitor the composition to a fraction of a monolayer. This technique needs to be both element-specific and surface-sensitive. RHEED-TRAXS is a leading contender as such a technique. The electron beam from a RHEED gun impinges on the sample at a small angle of incidence approximately equal to the critical angle for x-ray reflection. This geometry ensures that the measurement is extremely surface sensitive. This technique can be used to obtain both structural information, via RHEED, and chemical information, via x-ray detection. We are currently developing a compact RHEED-TRAXS using a state-of-the-art Si P-intrinsic-N (PIN) photodiode technology. We have used this system to investigate Ga and In coverage during the growth of GaN, and have observed Ga bi-layer evolution during growth, Mg destabilization of the Ga wetting layer, and significant In surface segregation. We are also investigating the in-situ, real-time composition measurements in complex oxide systems such as YMnO3 with promising initial results.In-situ cathodoluminescence (CL) occurring during RHEED is a strong candidate to determine the growth temperature and alloy composition for wide bandgap semiconductors. CL is easily detected up to and beyond typical growth temperatures for GaN and InGaN, accurately and reproducibly determining sample temperature during growth. Room CL measurement at room temperature can also be used as a means to check the quality of the substrate by comparing intensities of the GaN band edge energy peak and defect peaks. We have performed a detailed study of the factors influencing high temperature CL, and find the reproducibility of CL data and ability for fast CL scanning provide strong advantages for use in the growth of GaN films. CL could also be observed during growth using a ccd camera. This could be used to see temperature inhomogenaities, and potentially to map alloy composition fluctuations. Using tunable narrow bandpass optical filters, we can obtain a spatial/spectral map of sample CL. We will present CL images of samples at differing temperatures.This work was supported by the AFOSR MURI F49620-03-1-0330 and by ONR Grant N00014-02-1-0974.
Cardiac catheterisation is commonly used for diagnosis and therapeutic interventions in paediatric cardiology. The inherent risk of the procedure can result in unanticipated admissions to critical care. Our goals were to provide a qualitative description of characteristics and evaluation of children admitted unexpectedly to the cardiac critical care unit (CCCU).
A retrospective single centre review of cardiac catheterisation procedures was done between 1 January, 2003 and 30 April, 2013.
Of 9336 cardiac catheterisations performed, 146 (1.6%) were admitted from the catheterisation laboratory to the CCCU and met inclusion criteria. Of these 146 patients, 117 (1.3%) met criteria for unexpected admission and 29 (0.3%) were planned admissions. The majority admitted unexpectedly were below 1 year of age without co-morbidity aside from heart disease. Patients with planned admissions were significantly more likely to have single ventricle physiology, undergoing angiography or transferred for observation. Most unplanned admissions were triggered by interventional catheterisations or procedure-related complications. Patients received mechanical ventilation as the main CCCU management. Eighteen patients needed either cardiopulmonary resuscitation and/or extracorporeal membrane oxygenation during their catheterisation. About 106/117 (90.6%) patients survived to hospital discharge with no deaths in the planned admission group.
Admission to CCCU following cardiac catheterisation was uncommon and tended to occur in younger children undergoing interventional procedures. Outcomes did not differ between patients experiencing planned and unplanned CCCU admission. Ongoing development of risk stratification tools may help to decrease unplanned CCCU admissions. Further studies are needed to determine whether unplanned admission following paediatric cardiac catheterisation should be utilised as a quality indicator.
Background: Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultra-high frequency (UHF) spinal cord stimulation at 10kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. Methods: We studied the effects of conventional (130Hz) and UHF stimulation in five patients with Parkinson’s disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. Results: Motor performance improved in all six patients with UHF DBS. 10kHz stimulation at amplitudes ≥3.0mA appeared to be as effective as 130Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, p=0.110, N=90 trials). Interestingly, 10kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130Hz stimulation. Conclusions: Our results indicate that DBS at 10kHz produces clinical benefits while possibly reducing stimulation-induced adverse effects in patients with movement disorders.
Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI–GVII, with GII.4 being the most prevalent. However, in 2012–2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013–2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.
We present an account of why we decided to retract a paper. We discovered a lack of adherence to conventional trials registration, execution, interpretation and reporting, and consequently, with the authors, needed to correct the scientific record. We set out our responses in general to strengthen research integrity.
Declaration of interest
K.S.B. is Editor-in-Chief of the British Journal of Psychiatry. W.L., K.R.K. and S.M.L. are members of the senior editorial committee and the research integrity committee for the journal. In the past three years, S.M.L. has received research support from Janssen and Lundbeck, and personal support from Janssen, Otsuka and Sunovion.
Introduction: According to WHO, one third of patients aged ≥65 fall every year. Those falls account for 25% of all geriatric emergency department (ED) visits. Fear of falling (FOF) is common in older patients who sustained a fall and is associated with a decline in mobility and health issues for patients. We hypothesized that there is an association between FOF and return to ED (RTED) and future falls. Objective: To assess the relation between FOF and RTED and subsequent falls in older ED patients Methods: This research was conducted as part of the Canadian Emergency Team Initiative in elderly (CETIe) multicenter prospective cohort study from 2011 to 2016. Participants: Patients 65 years or older were assessed and discharged from ED following a minor trauma. They had to be independent in all basic activities of daily living and being able to communicate in English or French. Measures: Primary outcome was RTED and secondary outcome was subsequent falls. Both were self-reported at 3 and 6 months. Patients were stratified according to Short Falls Efficacy Scale International (SFES-I) score, assessing FOF in different situations. A total score is calculated to determine the mild, moderate or severe level of FOF. Previous falls and TUG were used to evaluate patients’ mobility. OARS, ISAR and SOF were used to evaluated patient frailty. Descriptive statistical were performed and multiple regression were performed to show the association between SFES-1 score and outcomes. Results: FOF was measured in 2899 participants, of which 2214 participated at the 3 months follow-up and 2009 participated at the 6 months follow-up. Odds Ratio (OR) of return to ED at 3 months was 1.10 for moderate FOF and 1.52 for severe FOF (Type 3 test p = 0.11). At 6 months, OR was 1.03 for moderate FOF and 1.25 for severe FOF (Type 3 test p = 0.63). OR of subsequent fall at 3 months was 1.80 for moderate FOF and 2.18 for severe FOF (Type 3 test p < 0.001). At 6 months, OR of subsequent fall was 1.63 for moderate FOF and 2.37 for severe FOF (Type 3 test p < 0.001). Conclusion: The multicenter cohort study showed that severe fear of falling is strongly associated with subsequent falls over the next 6 months following ED discharge, but not significantly associated with return to ED episodes. Further research should be done to analyze the association between severe FOF and RTED.
Remains of the North American water vole (Microtus richardsoni) have previously been recovered from late Pleistocene and Holocene deposits in southwestern Alberta, western Montana, and north-central Wyoming. All are within the historically documented modern range of the metapopulation occupying the Rocky Mountains; no ancient remains of this large microtine have previously been reported from the metapopulation occupying the Cascade Range. Four lower first molar specimens from the late Holocene Stemilt Creek Village archaeological site in central Washington here identified as water vole are from the eastern slope of the Cascade Range and are extralimital to the metapopulation found in those mountains. There is no taphonomic evidence indicating long-distance transport of the teeth, and modern trapping records suggest the local absence of water voles from the site area today is not a function of sampling error. The precise age of the Stemilt Creek Village water voles is obscure but climate change producing well-documented late Holocene advances of nearby alpine glaciers could have created habitat conditions conducive to the apparent modest shift in the range of the species represented by the remains.
A cost-effective fabrication method to engineer metamaterial structures with micrometersize features and novel mechanical properties, which are suitable for terahertz applications, is reported herein. The effective metamaterial parameter extraction procedure is employed with the Kramers-Kronig relation to analyze the effective parameters of single- and multilayer metamaterial structures.
We have developed a novel strategy for elaborating composite plasmonic nanomaterials in a well controlled manner. Combining several techniques commonly used in microelectronic engineering, namely sputtering deposition, thermal oxidation, ultra low energy ion implantation, focused ion beam lithography, thermal or laser annealing, we have obtained 3D patterned optical layers. Their spatial and spectral responses take benefit of optical interference, plasmonic resonance effects and coupling between excitations in both near and far field regime. Moreover these structures show high level of uniformity, reproducibility and stability, and they preserve flat and chemically uniform surfaces.
The second order nonlinear optical (NLO) properties of two different ionic selfassembled multilayer (ISAM) films combined with Ag nanoparticles have been investigated. The plasmon resonances in the Ag particles concentrate the incident light, markedly increasing in the NLO efficiencies of the films. We find that the efficiency enhancement is significantly larger in conventional ISAM films compared to films made using a hybrid covalent ISAM technique (HCISAM), even though the intrinsic bulk second order non-linear susceptibility (χ(2)) is much larger for HCISAM films. We attribute this to the interfaces in HCISAM films being much easier to disrupt by external perturbations such as the metal deposition by which the nanoparticles are fabricated. We conclude that because the plasmon decay length is very short, the plasmonic enhancement of NLO effects primarily occurs at and near the film-particle interface. To discern the importance of the interfaces, we surrounded thin ISAM and HCISAM films with NLOinactive buffer layers, which confirmed this hypothesis, particularly in the case of HCISAM films.