To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
The mass balance of Glacier de Sarennes, French Alps, has been measured since 1949, using the glaciological method based on core and ablation stake data, and area extrapolations, to find the overall glacier balance. The cumulative balance obtained in this way is very dependent on systematic errors that can increase linearly with the number, N, of measurement years, whereas random errors rise with . The volumetric-balance method based on aerial photogrammetry provides results whose errors do not depend on the number of years. This method was used to test field measurements for the period 1952–2003 and gives a mass balance of −32.30 ± 1.04 m w.e. compared to −34.89 ± 1.15 m w.e. based on field data. The discrepancy between the two methods is discussed on the basis of a careful error analysis. Moreover, the possibility of using the volumetric method to detect biases in field measurements is evaluated in terms of two types of errors. The number and locations of measurement sites required to account for all the spatial and temporal variabilities of the mass balance is discussed by variance analysis. Methodological implications and recommendations are presented to provide mass-balance measurements of the best possible accuracy.
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.
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 0.5m refracting telescope of the Van Vleck Observatory has been active in the determination of trigonometric parallaxes since its first observations in 1922. Its lenses were ground by C.A.R. Lundin of the Alvan Clark Co. for photographic use. Coma was minimized across the field and vignetting was also kept to a minimum. Partly as a consequence the focal curve is very steep in the blue and green regions of the spectrum, as is shown in Fig. 1. A Wratten No. 12 minus blue filter is used to filter out all wavelengths to the blue of about 5200 å. The region between 5200 å and 6000 å is very flat with the focal plane varying over a range of about one millimeter. Towards the red region it steepens, although not enough to impair images on photographic plates of emulsion types 103a-D and IIIa-F, the two in widespread use in recent years.
We review the state of the Onsala blind survey of the galactic plane, searching for new 6.7 GHz methanol masers. We also describe preliminary results of millimeter follow-up observations of the new detections and high resolution observations using the EVN. We conclude that blind surveys are important to complement targeted searches done until now and give the possibility to detect new classes of objects.
Observations show that glaciers around the world are in retreat and losing mass. Internationally coordinated for over a century, glacier monitoring activities provide an unprecedented dataset of glacier observations from ground, air and space. Glacier studies generally select specific parts of these datasets to obtain optimal assessments of the mass-balance data relating to the impact that glaciers exercise on global sea-level fluctuations or on regional runoff. In this study we provide an overview and analysis of the main observational datasets compiled by the World Glacier Monitoring Service (WGMS). The dataset on glacier front variations (∼42 000 since 1600) delivers clear evidence that centennial glacier retreat is a global phenomenon. Intermittent readvance periods at regional and decadal scale are normally restricted to a subsample of glaciers and have not come close to achieving the maximum positions of the Little Ice Age (or Holocene). Glaciological and geodetic observations (∼5200 since 1850) show that the rates of early 21st-century mass loss are without precedent on a global scale, at least for the time period observed and probably also for recorded history, as indicated also in reconstructions from written and illustrated documents. This strong imbalance implies that glaciers in many regions will very likely suffer further ice loss, even if climate remains stable.
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.
Measurements made during the Ross Ice Shelf Geophysical and Glaciological Survey (RIGGS, 1973–78) are used to determine the large-scale rheological conditions of the Ross Ice Shelf, Antarctica. Our method includes a numerical ice-shelf model based on the stress-equilibrium equations and control theory. We additionally perform a few tests on simplified geometries to investigate the precision of our method. Our results consist of a map of the depth-averaged viscosity of the central part of the Ross Ice Shelf to within an uncertainty of 20%. We find that the viscosity variations are consistent with Glen’s flow law. Application of a more realistic flow law in our study provides little enhancement of ice-shelf model accuracy until uncertainties associated with basal melting conditions and with temperature profiles at inflow boundaries are addressed. Finally, our results suggest a strong viscosity anomaly in the west-central part of the ice shelf, which is interpreted to be associated with changes in the dynamics of Ice Stream A or B at least 1000 years ago. This feature conforms to the prevailing notion that the West Antarctic ice streams are unsteady.
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.