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Anomalous right coronary artery from pulmonary artery (ARCAPA) is a rare congenital heart disease that can lead to abnormal coronary perfusion and a need for surgical repair. Here, we report the outcomes of patients who underwent ARCAPA surgery within the Pediatric Cardiac Care Consortium (PCCC), a North American registry of interventions for paediatric heart diseases. We queried the PCCC for patients undergoing surgical repair for ARCAPA at <18 years of age between 1982 and 2003. Outcomes were obtained from the PCCC and after linkage with the National Death Index (NDI) and the Organ Procurement and Transplantation Network (OPTN) through 2019. Twenty-four patients (males: 15) were identified having surgery for ARCAPA at a median age of 5.8 (IQR 2.7–10.3) years. Of them, 23 cases were considered “simple” (without major intracardiac disease) and one “complex” (co-existing with tetralogy of Fallot). Five patients presented with symptoms [chest pain (1), dyspnoea on exertion (2) or history of syncope (2)]; while the remaining 19 patients were referred for evaluation of either murmur or co-existing CHD. There was no in-hospital mortality after the surgical repair. Fourteen patients had sufficient identifiers for NDI/OPTN linkage; among them, only one death occurred from unrelated non-cardiac causes within a median period of 19.4 years of follow-up (IQR: 18–24.6). Outcomes were excellent after reimplantation up to 25 years later and further longitudinal monitoring is important to understand the interaction of pre-existing coronary pathology with the effects of ageing.
Metabolic syndrome and impaired insulin sensitivity may occur as side effects of atypical antipsychotic drugs. However, studies of peripheral insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) or oral glucose tolerance tests (OGTT) suggest that abnormal glucose metabolism is already present in drug-naive first-episode schizophrenia (DNFES). We hypothesized impairments of neuronal insulin signaling in DNFES.
To gain insight into neuronal insulin-signaling in vivo, we analyzed peripheral blood extracellular vesicles enriched for neuronal origin (nEVs). Phosphorylated insulin signal transduction serine-threonine kinases pS312-IRS-1, pY-IRS-1, pS473-AKT, pS9-GSK3β, pS2448-mTOR, pT389-p70S6K and respective total protein levels were determined in plasma nEVs from 48 DNFES patients and healthy matched controls after overnight fasting.
Upstream pS312-IRS-1 was reduced at trend level (p = 0.071; this condition may amplify IRS-1 signaling). Exploratory omnibus analysis of downstream serine-threonine kinases (AKT, GSK3β, mTOR, p70S6K) revealed lower phosphorylated/total protein ratios in DNFES vs. controls (p = 0.013), confirming decreased pathway activation. Post-hoc-tests indicated in particular a reduced phosphorylation ratio of mTOR (p = 0.027). Phosphorylation ratios of p70S6K (p = 0.029), GSK3β (p = 0.039), and at trend level AKT (p = 0.061), showed diagnosis-dependent statistical interactions with insulin blood levels. The phosphorylation ratio of AKT correlated inversely with PANSS-G and PANSS-total scores, and other ratios showed similar trends.
These findings support the hypothesis of neuronal insulin resistance in DNFES, small sample sizes notwithstanding. The counterintuitive trend towards reduced pS312-IRS-1 in DNFES may result from adaptive feedback mechanisms. The observed changes in insulin signaling could be clinically meaningful as suggested by their association with higher PANSS scores.
Guidelines recommend empowering patients and families to remind healthcare workers (HCWs) to perform hand hygiene (HH). The effectiveness of empowerment tools for patients and their families in Southeast Asia is unknown.
We performed a prospective study in a pediatric intensive care unit (PICU) of a Vietnamese pediatric referral hospital. With family and HCW input, we developed a visual tool for families to prompt HCW HH. We used direct observation to collect baseline HH data. We then enrolled families to receive the visual tool and education on its use while continuing prospective collection of HH data. Multivariable logistic regression was used to identify independent predictors of HH in baseline and implementation periods.
In total, 2,014 baseline and 2,498 implementation-period HH opportunities were observed. During the implementation period, 73 families were enrolled. Overall, HCW HH was 46% preimplementation, which increased to 73% in the implementation period (P < .001). The lowest HH adherence in both periods occurred after HCW contact with patient surroundings: 16% at baseline increased to 24% after implementation. In multivariable analyses, the odds of HCW HH during the implementation period were significantly higher than baseline (adjusted odds ratio [aOR], 2.94; 95% confidence interval [CI], 2.54–3.41; P < .001) after adjusting for observation room, HCW type, time of observation (weekday business hours vs evening or weekend), and HH moment.
The introduction of a visual empowerment tool was associated with significant improvement in HH adherence among HCWs in a Vietnamese PICU. Future research should explore acceptability and barriers to use of similar tools in low- and middle-income settings.
OBJECTIVES/SPECIFIC AIMS: Low cancer clinical trial (CCTs) enrollment may contribute to the poor survival improvement for adolescents and young adults (AYAs, aged 15–39 years) with cancer. Treatment site is thought to exacerbate this problem. This study evaluated whether differences in CCT availability explain lower CCT enrollment depending on treatment site for AYAs. METHODS/STUDY POPULATION: This prospective, observational cohort study was conducted at an academic children’s hospital and an adult cancer hospital, 2 affiliated sites within a NCI-designated Comprehensive Cancer Center over 13 months. In consecutive AYA patients newly diagnosed with cancer at both site, it was determined whether an appropriate CCT existed nationally, was available locally, and if enrollment occurred. The proportions of AYAs in these categories were compared by site using the χ2 test. RESULTS/ANTICIPATED RESULTS: Among 152 consecutive AYA patients, 68 and 84 were treated at the children’s hospital and adult cancer hospital, respectively. AYAs treated at the children’s hospital had similar CCT existence nationally compared with AYAs treated at the adult hospital [36/68 (52.9%) vs. 45/84 (53.6%), p=0.938]. However, a significantly higher percentage of children’s hospital treated AYAs than adult hospital treated AYAs had an available CCT [30/68 (44.1%) vs. 14/84 (16.7%), p<0.001]. Enrollment percentages were similarly low in both groups [8/68 (11.8%) vs. 6/84 (7.1%), p=0.327]. DISCUSSION/SIGNIFICANCE OF IMPACT: Significantly fewer AYAs treated at the adult hospital had a CCT available, but national existence was similar at both sites. This suggests that institutional barriers to opening CCT have more importance at adult centers.
Lateral memristors consisting of planar Ag electrodes (with sub-micrometer separation) supported on thin films of amorphous zinc-tin-oxide have been characterized. After an initial filament-forming process, each device exhibited volatile, resistive switching. In the low resistance state, the transport mechanism and conductance depended on prior activity and on the imposed current limit, mimicking biologic synaptic plasticity. Microscopic observations performed on each device revealed nanoscale filaments between the electrodes. These filaments were subject to Rayleigh instability and exhibited relaxation times determined by their effective radii. The relaxation times and on:off resistance ratios suggest suitability for threshold switching selector devices.
We introduce the asprilo1 framework to facilitate experimental studies of approaches addressing complex dynamic applications. For this purpose, we have chosen the domain of robotic intra-logistics. This domain is not only highly relevant in the context of today's fourth industrial revolution but it moreover combines a multitude of challenging issues within a single uniform framework. This includes multi-agent planning, reasoning about action, change, resources, strategies, etc. In return, asprilo allows users to study alternative solutions as regards effectiveness and scalability. Although asprilo relies on Answer Set Programming and Python, it is readily usable by any system complying with its fact-oriented interface format. This makes it attractive for benchmarking and teaching well beyond logic programming. More precisely, asprilo consists of a versatile benchmark generator, solution checker and visualizer as well as a bunch of reference encodings featuring various ASP techniques. Importantly, the visualizer's animation capabilities are indispensable for complex scenarios like intra-logistics in order to inspect valid as well as invalid solution candidates. Also, it allows for graphically editing benchmark layouts that can be used as a basis for generating benchmark suites.
Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups.
Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects.
The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants.
Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.
Suicide prevention organisations frequently use websites to educate the public, but evaluations of these websites are lacking.
To examine the effects of educative websites and the moderating effect of participant vulnerability.
A total of 161 adults were randomised to either view an educative website on suicide prevention or an unrelated website in a single-blinded randomised controlled trial (trial registration with the American Economic Association's registry: RCT-ID: 000924). The primary outcome was suicidal ideation; secondary outcomes were mood, suicide-prevention-related knowledge and attitudes towards suicide/seeking professional help. Data were collected using questionnaires before (T1), immediately after exposure (T2), and 1 week after exposure (T3) and analysed using linear mixed models.
No significant intervention effect was identified for the entire intervention group with regard to suicidal ideation, but a significant and sustained increase in suicide-prevention-related knowledge (T3v. T1P< 0.001, d = 1.12, 95% CI 0.96 to 1.28) and a non-sustained worsening of mood (P< 0.001, T2v. T1, d = −0.59, −0.75 to −0.43) were observed. Participants with increased vulnerability experienced a partially sustained reduction of suicidal ideation (T3v. T1, P<0.001, d = −0.34, −0.50 to −0.19).
Educative professional suicide prevention websites appeared to increase suicide-prevention-related knowledge, and among vulnerable individuals website exposure may be associated with a reduction of suicidal ideation.
This article describes a formal proof of the Kepler conjecture on dense sphere packings in a combination of the HOL Light and Isabelle proof assistants. This paper constitutes the official published account of the now completed Flyspeck project.
A 10-year-old boy presented with pain and soft tissue swelling of the left cheek. A CT scan demonstrated an extensive soft tissue mass centered in the left maxilla with associated cortical erosion of the left alveolar ridge and left maxillary sinus walls. Contralateral involvement of the right alveolar ridge and anterior maxillary sinus wall was also noted. Several teeth appeared to be “floating” within the maxilla. There was absence of adjacent soft tissue fat stranding (Fig. 9.1a–c).
A five-month-old infant presented with bi-parietal scalp swelling. CT of the head showed bi-parietal calvarial lytic lesions with associated soft tissue masses and a characteristic “beveled edge” appearance with greater destruction of the outer table of the calvarium relative to the inner table (Fig. 9.2a, b). On MRI, mixed T1 and T2 intensities and heterogeneous enhancement of the soft tissue mass was seen (Fig. 9.2c–e).
Langerhans cell histiocytosis (LCH) was confirmed pathologically in both cases.
To determine whether increases in contact isolation precautions are associated with decreased adherence to isolation practices among healthcare workers (HCWs).
Prospective cohort study from February 2009 to October 2009.
Eleven teaching hospitals.
One thousand thirteen observations conducted on HCWs. Additional data included the number of persons in isolation, types of HCWs, and hospital-specific contact precaution practices. Main outcome measures included compliance with individual components of contact isolation precautions (hand hygiene before and after patient encounter, donning of gown and glove upon entering a patient room, and doffing upon exiting) and overall compliance (all 5 measures together) during varying burdens of isolation.
Compliance with hand hygiene was as follows: prior to donning gowns/gloves, 37.2%; gowning, 74.3%; gloving, 80.1%; doffing of gowns/gloves, 80.1%; after gown/glove removal, 61%. Compliance with all components was 28.9%. As the burden of isolation increased (20% or less to greater than 60%), a decrease in compliance with hand hygiene (43.6%—4.9%) and with all 5 components (31.5%—6.5%) was observed. In multivariable analysis, there was an increase in noncompliance with all 5 components of the contact isolation precautions bundle (odds ratio [OR], 6.6 [95% confidence interval (CI), 1.15-37.44]; P = .03) and in noncompliance with hand hygiene prior to donning gowns and gloves (OR, 10.1 [95% CI, 1.84—55.54]; P = .008) associated with increasing burden of isolation.
As the proportion of patients in contact isolation increases, compliance with contact isolation precautions decreases. Placing 40% of patients under contact precautions represents a tipping point for noncompliance with contact isolation precautions measures.
Phosphorus is incorporated into single crystal diamond during epitaxial growth at higher concentrations on the (111) crystallographic surface than on the (001) crystallographic surface. To form n+-type regions in diamond for semiconductor devices it is beneficial to deposit on the (111) surface. However, diamond deposition is faster and of higher quality on the (001) surface. A preferential etch method is described that forms inverted pyramids on the (001) surface of a substrate diamond crystal, which opens (111) faces for improved phosphorus incorporation. The preferential etching occurs on the surface in regions where a nickel film is deposited. The etching is performed in a microwave generated hydrogen plasma operating at 160 Torr with the substrate temperature in the range of 800-950 °C. The epitaxial growth of diamond with high phosphorus concentrations exceeding 1020 cm-3 is performed using a microwave plasma-assisted chemical vapor deposition process. Successful growth conditions were achieved with a feedgas mixture of 0.25% methane, 500 ppm phosphine and hydrogen at a pressure of 160 Torr and a substrate temperature of 950-1000°C. The room temperature resistivity of the phosphorus-doped diamond is 120-150 Ω-cm and the activation energy is 0.027 eV.
Triticale possesses favourable agronomic attributes originating from both its wheat and rye progenitors, including high grain and biomass yields. Triticale, primarily used as animal feed in North America, is an excellent candidate for production of industrial bio-products. Little is known about the coordination of gene expression of rye and wheat genomes in this intergeneric hybrid, but significant DNA losses from the parental genomes have been reported. To clarify the regulation of gene expression in triticale, we carried out 454 sequencing of cDNAs obtained from root, leaf, stem and floral tissues in different lines of triticale and rye exhibiting different phenotypes and assembled reads into contigs. Related to the data assembly were the absence of reference genomes and the paucity of rye sequences in GenBank or other public databases. Consequently, we have sequenced cDNA libraries from roots, seedlings, leaves, floral tissues and immature seeds to facilitate the identification of triticale sequences originating from rye. To further characterize the wheat-derived cDNAs, we also developed a database close to 25,000 non-redundant full-length wheat coding sequence genes, based on existing databases and contigs that were verified against protein sequences from the grass genomes of Brachypodium distachyon, rice, sorghum and maize.
Two common problems with implantation after cancerous tumor resection are cancer recurrence and bacteria infection at the implant site. Tumor resection surgery sometimes can not remove all the cancerous cells, thus, cancer can return after implantation. In addition, bacteria infection is one of the leading causes of implant failure. Therefore, it is desirable to have anti-cancer and anti-bacterial molecules which both rapidly (for anti-infection purposes) and continuously (for anti-cancer purposes) are available at the implant site following implantation. Therefore, the objective of the present in vitro study was to create a multi-functional coating for anti-cancer and anti-bacterial orthopedic implant applications. Elemental selenium was chosen as the biologically active agent in this effort because of its known chemopreventive and anti-bacterial properties. To achieve that objective, titanium (Ti), a conventional orthopedic implant material was coated with selenium (Se) nanoclusters. Different coating densities were achieved by varying Se concentration in the reaction mixture. Titanium substrates coated with Se nanoclusters were shown to enhance healthy osteoblast (bone-forming cell) and inhibit cancerous osteoblast proliferation in co-culture experiments. Functions of S. epidermidis (one of the leading bacteria that infect implants) were inhibited on Ti coated with Se-nanoclusters compared to uncoated materials. Thus, this study provided for the first time a coating material (selenium nanoclusters) to the biomaterials’ community to promote healthy bone cells’ functions, inhibit cancer growth and prevent bacteria infection.
Current orthopedic implants have numerous problems that include poor osseointegration, stress shielding and wear debris-associated bone cell death. In addition, numerous patients receive orthopedic implants as a result of bone cancer resection, yet none of the current orthopedic materials are designed to prevent either the occurrence or reoccurrence of cancer. The objective of this study was to transform a traditional orthopedic material into an implant that can both restore bone and prevent bone cancer growth at the implant-tissue interface. Elemental selenium was chosen as the biologically active agent in this material because of its known chemopreventive and chemotherapeutic properties. It was found that when selenite salts were reduced by glutathione in the presence of an immersed substrate (titanium (Ti), stainless steel (SS) or ultra high molecular weigh polyethylene (UHMWPE)), elemental selenium nucleated and grew into adherent, hemispherical nanoclusters. For each type of substrate (Ti, SS and UHMWPE), three types of surfaces with different selenium surface densities were fabricated. The zero oxidation state of selenium was confirmed on Ti substrates by XPS profiles. Compared to uncoated Ti and SS substrates, the high-density selenium-coated surfaces inhibited cancerous bone cell functions while promoting healthy bone cell functions. Very little selenium was also found to release (about 250ppb) into the cell culture media after 3 days of immersion. These findings showed for the first time the potential of using selenium nanoclusters as a coating to transform a traditional orthopedic material into a bone cancer inhibiting implant.
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