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A simplified model is introduced to study finite-amplitude thermo-acoustic oscillations in
-periodic annular combustion devices. Such oscillations yield undesirable effects and can be triggered by a positive feedback between heat-release and pressure fluctuations. The proposed model, comprising the governing equations linearized in the acoustic limit, and with each burner modelled as a one-dimensional system with acoustic damping and a compact heat source, is used to study the instability caused by cross-sector coupling. The coupling between the sectors is included by solving the one-dimensional acoustic jump conditions at the locations where the burners are coupled to the annular chambers of the combustion device. The analysis takes advantage of the block-circulant structure of the underlying stability equations to develop an efficient methodology to describe the onset of azimuthally synchronized motion. A modal analysis reveals the dominance of global instabilities (encompassing the large-scale dynamics of the entire system), while a non-modal analysis reveals a strong response to harmonic excitation at forcing frequencies far from the eigenfrequencies, when the overall system is linearly stable. In all presented cases, large-scale, azimuthally synchronized (coupled) motion is observed. The relevance of the non-modal response is further emphasized by demonstrating the subcritical nature of the system’s Hopf point via an asymptotic expansion of a nonlinear model representing the compact heat source within each burner.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.
Child maltreatment has been associated with various cumulative risk factors. However, little is known about the extent to which genetic and environmental factors contribute to individual differences between parents in perpetrating child maltreatment. To estimate the relative contribution of genetic and environmental factors to perpetrating maltreatment we used a parent-based extended family design. Child-reported perpetrated maltreatment was available for 556 parents (283 women) from 63 families. To explore reporter effects (i.e., child perspective on maltreatment), child reports were compared to multi-informant reports. Based on polygenic model analyses, most of the variance related to the perpetration of physical abuse and emotional neglect was explained by common environmental factors (physical abuse: c2 = 59%, SE = 12%, p = .006; emotional neglect: c2 = 47%, SE = 8%, p < .001) whereas genetic factors did not significantly contribute to the model. For perpetrated emotional abuse, in contrast, genetic factors did significantly contribute to perpetrated emotional abuse (h2 = 33%, SE = 8%, p < .001), whereas common environment factors did not. Multi-informant reports led to similar estimates of genetic and common environmental effects on all measures except for emotional abuse, where a multi-informant approach yielded higher estimates of the common environmental effects. Overall, estimates of unique environment, including measurement error, were lower using multi-informant reports. In conclusion, our findings suggest that genetic pathways play a significant role in perpetrating emotional abuse, while physical abuse and emotional neglect are transmitted primarily through common environmental factors. These findings imply that interventions may need to target different mechanisms dependings on maltreatment type.
Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated.
We used bacterial 16S rRNA gene deep-sequencing, analysis, and quantification to profile entire bacterial populations on stethoscopes in use in an intensive care unit (ICU), including practitioner stethoscopes, individual-use patient-room stethoscopes, and clean unused individual-use stethoscopes. Two additional sets of practitioner stethoscopes were sampled before and after cleaning using standardized or practitioner-preferred methods.
Bacterial contamination levels were highest on practitioner stethoscopes, followed by patient-room stethoscopes, whereas clean stethoscopes were indistinguishable from background controls. Bacterial communities on stethoscopes were complex, and community analysis by weighted UniFrac showed that physician and patient-room stethoscopes were indistinguishable and significantly different from clean stethoscopes and background controls. Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8%–14% of contaminating bacterial sequences). Other HAI-related genera were also widespread although lower in abundance. Cleaning of practitioner stethoscopes resulted in a significant reduction in bacterial contamination levels, but these levels reached those of clean stethoscopes in only a few cases with either standardized or practitioner-preferred methods, and bacterial community composition did not significantly change.
Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities.
OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
An estimated 293,300 healthcare-associated cases of Clostridium difficile infection (CDI) occur annually in the United States. To date, research has focused on developing risk prediction models for CDI that work well across institutions. However, this one-size-fits-all approach ignores important hospital-specific factors. We focus on a generalizable method for building facility-specific models. We demonstrate the applicability of the approach using electronic health records (EHR) from the University of Michigan Hospitals (UM) and the Massachusetts General Hospital (MGH).
We utilized EHR data from 191,014 adult admissions to UM and 65,718 adult admissions to MGH. We extracted patient demographics, admission details, patient history, and daily hospitalization details, resulting in 4,836 features from patients at UM and 1,837 from patients at MGH. We used L2 regularized logistic regression to learn the models, and we measured the discriminative performance of the models on held-out data from each hospital.
Using the UM and MGH test data, the models achieved area under the receiver operating characteristic curve (AUROC) values of 0.82 (95% confidence interval [CI], 0.80–0.84) and 0.75 ( 95% CI, 0.73–0.78), respectively. Some predictive factors were shared between the 2 models, but many of the top predictive factors differed between facilities.
A data-driven approach to building models for estimating daily patient risk for CDI was used to build institution-specific models at 2 large hospitals with different patient populations and EHR systems. In contrast to traditional approaches that focus on developing models that apply across hospitals, our generalizable approach yields risk-stratification models tailored to an institution. These hospital-specific models allow for earlier and more accurate identification of high-risk patients and better targeting of infection prevention strategies.
Predicting recurrent Clostridium difficile infection (rCDI) remains difficult. METHODS. We employed a retrospective cohort design. Granular electronic medical record (EMR) data had been collected from patients hospitalized at 21 Kaiser Permanente Northern California hospitals. The derivation dataset (2007–2013) included data from 9,386 patients who experienced incident CDI (iCDI) and 1,311 who experienced their first CDI recurrences (rCDI). The validation dataset (2014) included data from 1,865 patients who experienced incident CDI and 144 who experienced rCDI. Using multiple techniques, including machine learning, we evaluated more than 150 potential predictors. Our final analyses evaluated 3 models with varying degrees of complexity and 1 previously published model.
Despite having a large multicenter cohort and access to granular EMR data (eg, vital signs, and laboratory test results), none of the models discriminated well (c statistics, 0.591–0.605), had good calibration, or had good explanatory power.
Our ability to predict rCDI remains limited. Given currently available EMR technology, improvements in prediction will require incorporating new variables because currently available data elements lack adequate explanatory power.
The illegal trade in rhinoceros horn, driven largely by the demand from East and South-east Asia, is a major impediment to the conservation of rhinoceroses globally. We surveyed the town of Mong La, in eastern Myanmar on the border with China, for the presence of rhinoceros horn. No rhinoceros horn was observed in 2006 or 2009, and other African wildlife was rare or absent. During visits in 2014 and 2015 we observed two horns, presumed to be of the white rhinoceros Ceratotherium simum, and one horn tip, small discs from the horn core, horn powder and horn bangles. Shops selling rhinoceros horn all specialized in high-end and high-value wildlife, mostly for decorative purposes, including whole elephant tusks, carved elephant ivory, carved hippopotamus Hippopotamus amphibius canines, and tiger Panthera tigris skins. Organized criminal syndicates are involved in the wildlife trade between Myanmar and Africa, possibly via China. Mong La's geographical position on the border with China, limited control by the central Myanmar Government, and the presence of the Chinese entertainment industry provide ideal conditions for a global wildlife trade hub catering for the Chinese market. Solutions require more intense collaboration between the Myanmar and Chinese authorities to curb the trade in African rhinoceros horn in this part of Asia.
Historically, community engagement (CE) in research has been implemented in the fields of public health, education and agricultural development. In recent years, international discussions on the ethical and practical goals of CE have been extended to human genomic research and biobanking, particularly in the African context. While there is some consensus on the goals and value of CE generally, questions remain about the effectiveness of CE practices and how to evaluate this. Under the auspices of the Human Heredity and Health in Africa Initiative (H3Africa), the H3Africa CE working group organized a workshop in Stellenbosch, South Africa in March 2016 to explore the extent to which communities should be involved in genomic research and biobanking and to examine various methods of evaluating the effectiveness of CE. In this paper, we present the key themes that emerged from the workshop and make a case for the development of a rigorous application, evaluation and learning around approaches for CE that promote a more systematic process of engaging relevant communities. We highlight the key ways in which CE should be embedded into genomic research and biobanking projects.
Atrazine has been the most widely used herbicide in North American
processing sweet corn for decades; however, increased restrictions in recent
years have reduced or eliminated atrazine use in certain production areas.
The objective of this study was to identify the best stakeholder-derived
weed management alternatives to atrazine in processing sweet corn. In field
trials throughout the major production areas of processing sweet corn,
including three states over 4 yr, 12 atrazine-free weed management
treatments were compared to three standard atrazine-containing treatments
and a weed-free check. Treatments varied with respect to herbicide mode of
action, herbicide application timing, and interrow cultivation. All
treatments included a PRE application of dimethenamid. No single weed
species occurred across all sites; however, weeds observed in two or more
sites included common lambsquarters, giant ragweed, morningglory species,
velvetleaf, and wild-proso millet. Standard treatments containing both
atrazine and mesotrione POST provided the most efficacious weed control
among treatments and resulted in crop yields comparable to the weed-free
check, thus demonstrating the value of atrazine in sweet corn production
systems. Timely interrow cultivation in atrazine-free treatments did not
consistently improve weed control. Only two atrazine-free treatments
consistently resulted in weed control and crop yield comparable to standard
treatments with atrazine POST: treatments with tembotrione POST either with
or without interrow cultivation. Additional atrazine-free treatments with
topramezone applied POST worked well in Oregon where small-seeded weed
species were prevalent. This work demonstrates that certain atrazine-free
weed management systems, based on input from the sweet corn growers and
processors who would adopt this technology, are comparable in performance to
standard atrazine-containing weed management systems.
A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7–27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29–23·4) and 5·65 (95% CI 1·09–29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.
The objective of this study was to report procedural characteristics and adverse events on the data collected in the IMproving Paediatric and Adult Congenital Treatment registry.
The IMproving Paediatric and Adult Congenital Treatment– registry is a catheterisation registry focussed on paediatric and adult patients with congenital heart disease who are undergoing diagnostic catheterisations and catheter-based interventions. This study reports procedural characteristics and adverse events of patients who have undergone selected catheterisation procedures from January, 2011 to June, 2013.
Demographic, clinical, procedural, and institutional data elements were collected at participating centres and entered via either a web-based platform or software provided by the American College of Cardiology-certified vendors, and were collected in a secure, centralised database. For the purpose of this study, procedures that were not classified as one of the ‘core’ IMproving Paediatric and Adult Congenital Treatment procedures originally chosen for additional data collection were identified and selected for further data analysis.
During the time frame of data collection, a total of 8021 cases were classified as other procedures and/or multiple procedures. The most commonly performed case types – isolated or in combination with other procedures – were right ventricular biopsy in 3433 (42.8%), conduit/MPA interventions in 979 (12.3%), and systemic pulmonary artery collateral occlusion in 601 (7.5%). For the whole cohort, adverse events of any severity occurred in 957 (12.0%) cases, whereas major adverse events occurred in 113 (1.4%) cases; six patients (0.1%) died in the catheterisation laboratory.
The IMproving Paediatric and Adult Congenital Treatment registry has provided important data on the frequency and spectrum of cardiac catheterisation procedures performed in the present era. For many procedures, more data and work are needed to identify more subtle differences between case categories, especially as it relates to the incidence of major adverse events, and to further develop a risk-adjustment methodology to allow equitable comparisons among institutions.
Suicide is a leading cause of death for young people. Children living in sub-Saharan Africa, where HIV rates are disproportionately high, may be at increased risk.
To identify predictors, including HIV status, of suicidal ideation and behaviour in Rwandan children aged 10–17.
Matched case–control study of 683 HIV-positive, HIV-affected (seronegative children with an HIV-positive caregiver), and unaffected children and their caregivers.
Over 20% of HIV-positive and affected children engaged in suicidal behaviour in the previous 6 months, compared with 13% of unaffected children. Children were at increased risk if they met criteria for depression, were at high-risk for conduct disorder, reported poor parenting or had caregivers with mental health problems.
Policies and programmes that address mental health concerns and support positive parenting may prevent suicidal ideation and behaviour in children at increased risk related to HIV.
The Critically Endangered Black-winged Myna Acridotheres melanopterus is being pushed towards the brink of extinction in Indonesia due to continued demand for it as a cage bird and the lack of enforcement of national laws set in place to protect it. The trade in this species is largely to supply domestic demand, although an unknown level of international demand also persists. We conducted five surveys of three of Indonesia’s largest open bird markets (Pramuka, Barito and Jatinegara), all of which are located in the capital Jakarta, between July 2010 and July 2014. No Black-winged Mynas were observed in Jatinegara, singles or pairs were observed during every survey in Barito, whereas up to 14 birds at a time were present at Pramuka. The average number of birds observed per survey is about a quarter of what it was in the 1990s when, on average, some 30 Black-winged Mynas were present at Pramuka and Barito markets. Current asking prices in Jakarta are high, with unbartered quotes averaging USD 220 per bird. Our surveys of the markets in Jakarta illustrate an ongoing and open trade. Dealers blatantly ignore national legislation and are fearless of enforcement actions. Commercial captive breeding is unlikely to remove pressure from remaining wild populations of Black-winged Mynas. Efforts to end the illegal trade in this species and to allow wild populations to recover are urgently needed. We also recommend the immediate inclusion of Black-winged Mynas in Appendix III of CITES to allow for international support to Indonesia in clamping down on international trade of the species.
Systematic collecting through the upper Wenlock (upper Homerian) and lower Ludlow (Gorstian and lowermost Ludfordian) Silurian rock succession of the Long Mountain, Powys, Wales, identifies some 48 chitinozoan species that distinguish four biozones, two subzones and an interregnum. Consideration of the chitinozoan biozones together with those of the graptolites enables a local three-fold subdivision of the late Homerian lundgreni graptolite Biozone, and the distinction of lower and upper intervals for the Gorstian incipiens graptolite Biozone. The base of the Ludlow Series in the Long Mountain more or less equates to the base of the Cingulochitina acme chitinozoan Biozone, although no key chitinozoan first or last appearance datums are associated with the series boundary itself. The new graptolite–chitinozoan biozonation allows enhanced correlation between upper Wenlock and lower Ludlow sedimentary deposits of the Lower Palaeozoic Welsh depositional basin and those of the palaeo-shelf in the stratotype Wenlock and Ludlow areas of Shropshire. Chitinozoans seem affected by the phenomena that caused the late Wenlock ‘Mulde extinction’ in graptolites but, with the final disappearance of 9 species and re-appearance of 11 species following an interval of overall low diversity, they seem to have suffered less severely than their macro-zooplanktonic contemporaries.
Bradoriids are small bivalved arthropods that had global distribution for about 20 million years beginning at Cambrian Epoch 2 (c. 521 Ma). The majority of bradoriids are considered to be benthic, favouring oxygenated waters, as suggested by their anatomy, lithofacies distribution, faunal associates and provinciality. Most bradoriids were extinct by the end of the Drumian Age (middle of Cambrian Epoch 3). The post-Drumian is characterized by widespread dysoxic shelf lithofacies in southern Britain and Scandinavia and by the abundance of phosphatocopid arthropods. This interval is also associated with two bradoriid species with wide intercontinental distribution: Anabarochilina primordialis, which had a geographical range from the palaeo-tropics to high southern palaeo-latitude, and Anabarochilina australis, which extended through the palaeo-tropics from Laurentia to Gondwana. The wide environmental and geographical range of these species, coupled with a carapace anatomy that suggests an active lifestyle, is used to infer a zooplanktonic lifestyle. A possible driver of this widespread Cambrian bradoriid zooplankton was sea-level rise coupled to the periodic spread of low oxygen conditions onto continental shelves, acting in tandem with anatomical pre-adaptations for swimming. Parallels exist with the myodocope ostracod colonization of the water column during Silurian time, which may also have been influenced by extrinsic environmental controls acting on anatomical pre-adaptations for swimming. Similar biological and environmental mechanisms may have facilitated arthropod zooplankton colonizations across Phanerozoic time.