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In 2018, the Neurodevelopmental and Psychosocial Interventions Working Group of the Cardiac Neurodevelopmental Outcome Collaborative convened through support from an R13 grant from the National Heart, Lung, and Blood Institute to survey the state of neurodevelopmental and psychosocial intervention research in CHD and to propose a slate of critical questions and investigations required to improve outcomes for this growing population of survivors and their families. Prior research, although limited, suggests that individualised developmental care interventions delivered early in life are beneficial for improving a range of outcomes including feeding, motor and cognitive development, and physiological regulation. Interventions to address self-regulatory, cognitive, and social-emotional challenges have shown promise in other medical populations, yet their applicability and effectiveness for use in individuals with CHD have not been examined. To move this field of research forward, we must strive to better understand the impact of neurodevelopmental and psychosocial intervention within the CHD population including adapting existing interventions for individuals with CHD. We must examine the ways in which dedicated cardiac neurodevelopmental follow-up programmes bolster resilience and support children and families through the myriad transitions inherent to the experience of living with CHD. And, we must ensure that interventions are person-/family-centred, inclusive of individuals from diverse cultural backgrounds as well as those with genetic/medical comorbidities, and proactive in their efforts to include individuals who are at highest risk but who may be traditionally less likely to participate in intervention trials.
We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.
Identifying factors that influence the functional outcome is an important goal in schizophrenia research. The 22q11.2 deletion syndrome (22q11DS) is a unique genetic model with high risk (20–25%) for schizophrenia. This study aimed to identify potentially targetable domains of neurocognitive functioning associated with functional outcome in adults with 22q11DS.
We used comprehensive neurocognitive test data available for 99 adults with 22q11DS (n = 43 with schizophrenia) and principal component analysis to derive four domains of neurocognition (Verbal Memory, Visual and Logical Memory, Motor Performance, and Executive Performance). We then investigated the association of these neurocognitive domains with adaptive functioning using Vineland Adaptive Behavior Scales data and a linear regression model that accounted for the effects of schizophrenia status and overall intellectual level.
The regression model explained 46.8% of the variance in functional outcome (p < 0.0001). Executive Performance was significantly associated with functional outcome (p = 0.048). Age and schizophrenia were also significant factors. The effects of Executive Performance on functioning did not significantly differ between those with and without psychotic illness.
The findings provide the impetus for further studies to examine the potential of directed (early) interventions targeting Executive Performance to improve long-term adaptive functional outcome in individuals with, or at high risk for, schizophrenia. Moreover, the neurocognitive test profiles may benefit caregivers and clinicians by providing insight into the relative strengths and weaknesses of individuals with 22q11DS, with and without psychotic illness.
Neurodevelopmental impairment is increasingly recognised as a potentially disabling outcome of CHD and formal evaluation is recommended for high-risk patients. However, data are lacking regarding the proportion of eligible children who actually receive neurodevelopmental evaluation, and barriers to follow-up are unclear. We examined the prevalence and risk factors associated with failure to attend neurodevelopmental follow-up clinic after infant cardiac surgery.
Survivors of infant (<1 year) cardiac surgery at our institution (4/2011-3/2014) were included. Socio-demographic and clinical characteristics were evaluated in neurodevelopmental clinic attendees and non-attendees in univariate and multivariable analyses.
A total of 552 patients were included; median age at surgery was 2.4 months, 15% were premature, and 80% had moderate–severe CHD. Only 17% returned for neurodevelopmental evaluation, with a median age of 12.4 months. In univariate analysis, non-attendees were older at surgery, had lower surgical complexity, fewer non-cardiac anomalies, shorter hospital stay, and lived farther from the surgical center. Non-attendee families had lower income, and fewer were college graduates or had private insurance. In multivariable analysis, lack of private insurance remained independently associated with non-attendance (adjusted odds ratio 1.85, p=0.01), with a trend towards significance for distance from surgical center (adjusted odds ratio 2.86, p=0.054 for ⩾200 miles).
The majority of infants with CHD at high risk for neurodevelopmental dysfunction evaluated in this study are not receiving important neurodevelopmental evaluation. Efforts to remove financial/insurance barriers, increase access to neurodevelopmental clinics, and better delineate other barriers to receipt of neurodevelopmental evaluation are needed.
Five cases of STEC O157 phage type (PT) 21/28 reported consumption of raw cows' drinking milk (RDM) produced at a dairy farm in the South West of England. STEC O157 PT21/28 was isolated from faecal specimens from milking cows on the implicated farm. Whole genome sequencing (WGS) showed that human and cattle isolates were the same strain. Further analysis of WGS data confirmed that sequences of isolates from an additional four cases (who did not report consumption of RDM when first questioned) fell within the same five single nucleotide polymorphism cluster as the initial five cases epidemiologically linked to the consumption of RDM. These four additional cases identified by WGS were investigated further and were, ultimately, associated with the implicated farm. The RDM outbreak strain encoded stx2a, which is associated with increased pathogenicity and severity of symptoms. Further epidemiological analysis showed that 70% of isolates within a wider cluster containing the outbreak strain were from cases residing in, or linked to, the same geographical region of England. During this RDM outbreak, use of WGS improved case ascertainment and provided insights into the evolution of a highly pathogenic clade of STEC O157 PT21/28 stx2a associated with the South West of England.
Clinical databases in congenital and paediatric cardiac care provide a foundation for quality improvement, research, policy evaluations and public reporting. Structured audits verifying data integrity allow database users to be confident in these endeavours. We report on the initial audit of the Pediatric Cardiac Critical Care Consortium (PC4) clinical registry.
Materials and methods
Participants reviewed the entire registry to determine key fields for audit, and defined major and minor discrepancies for the audited variables. In-person audits at the eight initial participating centres were conducted during a 12-month period. The data coordinating centre randomly selected intensive care encounters for review at each site. The audit consisted of source data verification and blinded chart abstraction, comparing findings by the auditors with those entered in the database. We also assessed completeness and timeliness of case submission. Quantitative evaluation of completeness, accuracy, and timeliness of case submission is reported.
We audited 434 encounters and 29,476 data fields. The aggregate overall accuracy was 99.1%, and the major discrepancy rate was 0.62%. Across hospitals, the overall accuracy ranged from 96.3 to 99.5%, and the major discrepancy rate ranged from 0.3 to 0.9%; seven of the eight hospitals submitted >90% of cases within 1 month of hospital discharge. There was no evidence for selective case omission.
Based on a rigorous audit process, data submitted to the PC4 clinical registry appear complete, accurate, and timely. The collaborative will maintain ongoing efforts to verify the integrity of the data to promote science that advances quality improvement efforts.
Genetic testing in psychiatry promises to improve patient care through
advances in personalised medicine. However, there are few clinically
To determine whether patients with a well-established genetic subtype of
schizophrenia show a different response profile to the antipsychotic
clozapine than those with idiopathic schizophrenia.
We retrospectively studied the long-term safety and efficacy of clozapine
in 40 adults with schizophrenia, half with a 22q11.2 deletion (22q11.2DS
group) and half matched for age and clinical severity but molecularly
confirmed to have no pathogenic copy number variant (idiopathic
Both groups showed similar clinical improvement and significant
reductions in hospitalisations, achieved at a lower median dose for those
in the 22q11.2DS group. Most common side-effects were similarly prevalent
between the two groups, however, half of the 22q11.2DS group experienced
at least one rare serious adverse event compared with none of the
idiopathic group. Many were successfully retried on clozapine.
Individuals with 22q11.2DS-schizophrenia respond as well to clozapine
treatment as those with other forms of schizophrenia, but may represent a
disproportionate number of those with serious adverse events, primarily
seizures. Lower doses and prophylactic (for example anticonvulsant)
management strategies can help ameliorate side-effect risks. This first
systematic evaluation of antipsychotic response in a genetic subtype of
schizophrenia provides a proof-of-principle for personalised medicine and
supports the utility of clinical genetic testing in schizophrenia.
Some of the illustrative concepts for the disposal of intermediate-level waste in a geological disposal facility in the UK employ a cementitious backfill around the waste packages. The concept for higher strength rocks would use a highly alkaline backfill composed of Portland cement (now known as CEM I), hydrated lime and limestone flour, referred to as Nirex reference vault backfill (NRVB).
This paper reports a study of the extensive leaching of cured NRVB in a range of generic leachant compositions (deionized water, 0.1 M and 1 M NaCl solutions) under flow-through conditions using a flexible wall permeameter. The experiments were designed to run for up to two years and to pass at least 1000 volumes of leachant (defined as the cumulative leachate volume produced/NRVB solid specimen volume) through the NRVB samples. Results for the pH evolution profiles of the leachates and the microstructural analysis of the unleached and leached samples are presented.
Hafnium oxide-based resistive memory devices have been fabricated on copper bottom electrodes. The HfOx active layers in these devices were deposited by atomic layer deposition at 250 °C with tetrakis(dimethylamido)hafnium(IV) as the metal precursor and an O2 plasma as the reactant. Depth profiles of the HfOx by x-ray photoelectron spectroscopy and secondary ion mass spectroscopy revealed a copper concentration on the order of five atomic percent throughout the HfOx film. This phenomenon has not been previously reported in resistive switching literature and therefore may have gone unnoticed by other investigators. The MIM structures fabricated from the HfOx exhibited non-polar behavior, independent of the top metal electrode (Ni, Pt, Al, Au). These results are analogous to the non-polar switching behavior observed by Yang et al.  for intentionally Cu-doped HfOx resistive memory devices. The distinguishing characteristic of the material structure produced in this research is that the copper concentration increases to 60 % in a conducting surface copper oxide layer ~20 nm thick. Lastly, the results from both sweep- and pulse-mode current-voltage measurements are presented and preliminary work on fabricating sub-100 nm devices is summarized.
Symptomatic extracranial internal carotid artery stenosis poses a high short-time risk of ischemic cerebral stroke, as high as 20% to 30% in the first three months. Timely performed carotid endarterectomy (CEA) has been shown to be highly effective in reducing this risk although, in recent years, there has been great interest in replacing this procedure with less invasive carotid angioplasty and stenting (CAS). In this update we review recent studies and provide recommendations regarding the indications, methods and timing of surgical intervention as well as the anaesthetic management of CEA, and we report on recently published randomized controlled trials comparing CEA to CAS. We also provide recommendations regarding the sometime neglected but important medical management of patients undergoing carotid intervention, including antithrombotic and antihypertension therapy, lipid lowering agents, assistance with smoking cessation, and diabetes control.
The clinical significance of different genetic subtypes or assemblages of Giardia lamblia is uncertain. Cases of giardiasis in south-west London between 1999 and 2005 were studied, comparing molecular-typing results with clinical and epidemiological findings from routine surveillance. We identified 819 cases, of whom 389 returned surveillance questionnaires. A subset of 267 faecal samples was submitted for typing by sequencing of the triose phosphate isomerase (tpi) and ribosomal RNA genes, and/or a separate duplex PCR of the tpi gene. Typing was successful in 199 (75%) samples by at least one of the molecular methods. Assemblage A accounted for 48 (24%) samples and Assemblage B for 145 (73%); six (3%) were mixed. Both assemblages had similar seasonality, age distribution and association with travel. Clinical features were available for 59 successfully typed cases: both assemblages caused similar illness, but Assemblage A was significantly more frequently associated with fever than Assemblage B.
The current study examined whether a traditional exposure-based treatment for blood-injection-injury (BII) phobia would be effective at reducing disgust responses to BII stimuli and whether the addition of modules targeting disgust would provide incremental efficacy. Participants, many of whom reported subclinical BII phobia symptoms, underwent one of two single-session exposure protocols, one targeting fear alone, and the other targeting both fear and disgust. Both treatments consisted of education components (fear-only or fear-disgust) and in vivo exposure (fear-only or fear-disgust). Both the fear-only and the fear-disgust treatment groups significantly decreased fear and avoidance behaviour toward BII stimuli over time. The two groups also experienced similar reductions in disgust responses to BII-related stimuli and global as well as domain-specific disgust sensitivity. The effect sizes indicated that the fear-disgust group evidenced greater reduction in symptoms than did the fear-only group. The implications of the results for models of phobia maintenance and treatment are discussed.
We evaluated the performance of the food-frequency questionnaire (FFQ) administered to participants in the US NIH–AARP (National Institutes of Health–American Association of Retired Persons) Diet and Health Study, a cohort of 566 404 persons living in the USA and aged 50–71 years at baseline in 1995.
The 124-item FFQ was evaluated within a measurement error model using two non-consecutive 24-hour dietary recalls (24HRs) as the reference.
Participants were from six states (California, Florida, Pennsylvania, New Jersey, North Carolina and Louisiana) and two metropolitan areas (Atlanta, Georgia and Detroit, Michigan).
A subgroup of the cohort consisting of 2053 individuals.
For the 26 nutrient constituents examined, estimated correlations with true intake (not energy-adjusted) ranged from 0.22 to 0.67, and attenuation factors ranged from 0.15 to 0.49. When adjusted for reported energy intake, performance improved; estimated correlations with true intake ranged from 0.36 to 0.76, and attenuation factors ranged from 0.24 to 0.68. These results compare favourably with those from other large prospective studies. However, previous biomarker-based studies suggest that, due to correlation of errors in FFQs and self-report reference instruments such as the 24HR, the correlations and attenuation factors observed in most calibration studies, including ours, tend to overestimate FFQ performance.
The performance of the FFQ in the NIH–AARP Diet and Health Study, in conjunction with the study’s large sample size and wide range of dietary intake, is likely to allow detection of moderate (≥1.8) relative risks between many energy-adjusted nutrients and common cancers.
Auger Electron Spectroscopy (AES) is one of the few techniques that has surface sensitivity and small analysis volume to make it the ideal analytical technique for the compositional characterization of submicron defects. However, the integration of defect inspections at only a few processing steps during device fabrication results in the detection of many buried defects. In order to identify these defects, it is necessary to determine their composition. Combined with Focused Ion Beam (FIB) technique to expose the cross section of the buried defect, Auger analysis provides accurate identification of buried defects that are critical for quickly ramping to higher yields and recovering from yield excursions. This paper reports two examples of the use of AES combined with FIB to diagnose processing problems.
Magnetoresistive random-access memory (MRAM) is a new memory technology that is nearing commercialization. MRAM integrates a magnetic tunnel junction (MTJ) device with standard silicon-based microelectronics, resulting in a combination of qualities not found in other memory technologies. For example, MRAM is nonvolatile, has unlimited read and write endurance, and is capable of high-speed read and write operations. In this article, we will describe the fundamentals of an MTJ-based MRAM as well as recent important technology developments in the areas of magnetic materials and memory cell architecture. In addition, we will compare the present and future capabilities of MRAM to those of existing memory technologies such as static RAM and flash memory.
Hemodialysis-dependent patients are an important VRE source. After implementation of active surveillance for VRE targeting hemodialysis patients, the hospital-wide nosocomial VRE rate increased by 41%, but decreased by 41% among non-hemodialysis patients (P = .05). To assess the effectiveness of active surveillance, patients undergoing active surveillance should be analyzed separately from other patients.
The band-gap of indium nitride has long been believed to be about 1.9eV with slight variations due to band-tailing in polycrystalline samples and degenerate doping. Recently, other values as low as 0.7 eV have apparently been observed. We have compared samples spanning this apparent range of band-gap using secondary ion mass spectroscopy (SIMS), X-ray Photoelectron Spectroscopy (XPS) and heavy ion elastic recoil detection analysis (ERDA), in conjunction with spectral optical density measurements. Once structural inhomogeneiteies are taken into account, we show that much of the conflicting data are compatible with direct photoionisation with a threshold energy of about 1.0eV. This feature was first reported in polycrystalline indium nitride over 15 years ago and attributed to a ∣p> like defect state. We ask whether the feature may instead be a direct band-gap.
PRD1 is a ds-DNA bacteriophage from the Tectiviridae family with an unusual structural feature: the viral genome is enclosed by a protein-rich membrane, which is in turn enclosed by an external icosahedral protein shell (capsid). Three-dimensional reconstructions from cryo-electron microscopy (cryo-EM) images have revealed the structure of the PRD1 capsid at moderate resolution (28 Å), while X-ray crystallographic studies have recently provided a high resolution (1.85 Å) picture of the major coat protein, P3. We have now combined these results from different imaging methods to obtain a more detailed understanding of the virion organization. The combination has been made in a cyclic process: a preliminary fitting of the atomic structure of P3 to each one of its independent positions in the cryo-EM maps of the capsids provided initial models that could be used to improve the reconstructions; the refined maps then served as a base frame for an optimized fit. This process allows us to study the viral particle structure at “quasi-atomic” resolution.