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 firstname.lastname@example.org
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.
The control of stationary convective instabilities in the rotating disk boundary layer via a time-periodic modulation of the disk rotation rate is investigated. The configuration provides an archetypal example of a three-dimensional temporally periodic boundary layer, encompassing both the von Kármán and Stokes boundary layers. A velocity–vorticity formulation of the governing perturbation equations is deployed, together with a numerical procedure that utilises the Chebyshev-tau method. Floquet theory is used to determine the linear stability properties of these time-periodic flows. The addition of a time-periodic modulation to the otherwise steady disk rotation rate establishes a stabilising effect. In particular, for a broad range of modulation frequencies, the growth of the stationary convective instabilities is suppressed and the critical Reynolds number for the onset of both the cross-flow and Coriolis instabilities is raised to larger values than that found for the steady disk without modulation. An energy analysis is undertaken, where it is demonstrated that time-periodic modulation induces a reduction in the Reynolds stress energy production and an increase in the viscous dissipation across the boundary layer. Comparisons are made with other control techniques, including distributed surface roughness and compliant walls.
This paper describes a computational investigation of multimode instability growth and multimaterial mixing induced by multiple shock waves in a high-energy-density (HED) environment, where pressures exceed 1 Mbar. The simulations are based on a series of experiments performed at the National Ignition Facility (NIF) and designed as an HED analogue of non-HED shock-tube studies of the Richtmyer–Meshkov instability and turbulent mixing. A three-dimensional computational modelling framework is presented. It treats many complications absent from canonical non-HED shock-tube flows, including distinct ion and free-electron internal energies, non-ideal equations of state, radiation transport and plasma-state mass diffusivities, viscosities and thermal conductivities. The simulations are tuned to the available NIF data, and traditional statistical quantities of turbulence are analysed. Integrated measures of turbulent kinetic energy and enstrophy both increase by over an order of magnitude due to reshock. Large contributions to enstrophy production during reshock are seen from both the baroclinic source and enstrophy–dilatation terms, highlighting the significance of fluid compressibility in the HED regime. Dimensional analysis reveals that Reynolds numbers and diffusive Péclet numbers in the HED flow are similar to those in a canonical non-HED analogue, but conductive Péclet numbers are much smaller in the HED flow due to efficient thermal conduction by free electrons. It is shown that the mechanism of electron thermal conduction significantly softens local spanwise gradients of both temperature and density, which causes a minor but non-negligible decrease in enstrophy production and small-scale mixing relative to a flow without this mechanism.
ABSTRACT IMPACT: Circadian disruption is known to cause significant human pathology but has not been evaluated in pancreas cancer carcinogenesis; through understanding how disruption of circadian rhythms can lead to pancreas cancer development and spread, preventive and therapeutic strategies can be devised. OBJECTIVES/GOALS: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer due to early spread and poor response to therapy. Identifying factors driving PDAC growth could lead to new therapeutic strategies. Thus, we evaluated the extent to which circadian rhythm disruption, a factor strongly associated with cancer formation, contributes to PDAC pathogenesis. METHODS/STUDY POPULATION: To achieve the objective, we evaluated mice with pancreas lineage Kras-mutation (KC mice), which are predisposed to develop the full spectrum of pancreas cancer precursor lesions (pancreatic intra-epithelial neoplasia or PANIN-1, 2, 3) and PDAC. We subjected KC mice to a light-dark phase shift protocol known to induce circadian disruption (KCCD, n = 18), and another group to standard lighting conditions (KCNC, n = 31), with equal numbers of males and females in each group. The mice were allowed access to food and water ad libitum until sacrifice at age 9 months. Histopathologic evaluation of the pancreas was then performed to assess for pancreatic inflammation, pancreatic precursor lesions (PANIN) and PDAC. Fisher’s Exact Test was used to evaluate differences in incidence. RESULTS/ANTICIPATED RESULTS: As expected, both groups of mice demonstrated 100% incidence of chronic pancreatitis and PANIN-1 (low-grade precursor lesion) at age 9 months. This is consistent with the KC phenotype. However, the KCCD mice demonstrated a significant increase in acute pancreatic inflammation (61.1% vs 19.4%, p = 0.005) compared to KCNC mice. Furthermore, intermediate grade precursor lesions (PANIN-2) were also significantly increase in the KCCD mice (38.9% vs 6.5%, p = 0.006). Incidence of high-grade precursor lesions (PANIN-3, or carcinoma in situ: 22.2% vs 9.7%) and PDAC (27% vs 19%) were also increased, but these were not statistically significant. These results are notable given the established progression from higher grade premalignant PANIN lesions (PANIN-2, PANIN-3) to PDAC. DISCUSSION/SIGNIFICANCE OF FINDINGS: Insight into how circadian disruption leads to increased PANIN-2 formation and increase in acute inflammation may be advantageous for understanding circadian disruption in PDAC carcinogenesis. The circadian clock is present in immune cells and disruption can induce immune dysregulation. This mechanism will be evaluated in follow up studies.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Antibiotics are among the most common medications prescribed in nursing homes. The annual prevalence of antibiotic use in residents of nursing homes ranges from 47% to 79%, and more than half of antibiotic courses initiated in nursing-home settings are unnecessary or prescribed inappropriately (wrong drug, dose, or duration). Inappropriate antibiotic use is associated with a variety of negative consequences including Clostridioides difficile infection (CDI), adverse drug effects, drug–drug interactions, and antimicrobial resistance. In response to this problem, public health authorities have called for efforts to improve the quality of antibiotic prescribing in nursing homes.
Through diversity of composition, sequence, and interfacial structure, hybrid materials greatly expand the palette of materials available to access novel functionality. The NSF Division of Materials Research recently supported a workshop (October 17–18, 2019) aiming to (1) identify fundamental questions and potential solutions common to multiple disciplines within the hybrid materials community; (2) initiate interfield collaborations between hybrid materials researchers; and (3) raise awareness in the wider community about experimental toolsets, simulation capabilities, and shared facilities that can accelerate this research. This article reports on the outcomes of the workshop as a basis for cross-community discussion. The interdisciplinary challenges and opportunities are presented, and followed with a discussion of current areas of progress in subdisciplines including hybrid synthesis, functional surfaces, and functional interfaces.
We examined Clostridioides difficile infection (CDI) prevention practices and their relationship with hospital-onset healthcare facility-associated CDI rates (CDI rates) in Veterans Affairs (VA) acute-care facilities.
From January 2017 to February 2017, we conducted an electronic survey of CDI prevention practices and hospital characteristics in the VA. We linked survey data with CDI rate data for the period January 2015 to December 2016. We stratified facilities according to whether their overall CDI rate per 10,000 bed days of care was above or below the national VA mean CDI rate. We examined whether specific CDI prevention practices were associated with an increased risk of a CDI rate above the national VA mean CDI rate.
All 126 facilities responded (100% response rate). Since implementing CDI prevention practices in July 2012, 60 of 123 facilities (49%) reported a decrease in CDI rates; 22 of 123 facilities (18%) reported an increase, and 41 of 123 (33%) reported no change. Facilities reporting an increase in the CDI rate (vs those reporting a decrease) after implementing prevention practices were 2.54 times more likely to have CDI rates that were above the national mean CDI rate. Whether a facility’s CDI rates were above or below the national mean CDI rate was not associated with self-reported cleaning practices, duration of contact precautions, availability of private rooms, or certification of infection preventionists in infection prevention.
We found considerable variation in CDI rates. We were unable to identify which particular CDI prevention practices (i.e., bundle components) were associated with lower CDI rates.
OBJECTIVES/SPECIFIC AIMS: 1) Determine the mutational landscape, including translocation, mutations and mutational signatures as well as copy number variations of pPCL and identify significant differences to non pPCL MM. 2) Determine whether genetic changes pertinent to pPCL could be explored as therapeutic targets to improve the dismal prognosis of this patient population. METHODS/STUDY POPULATION: Samples from overall 19 pPCL patients that presented to the Myeloma Center, UAMS between 2000-2018 were used for this study. We performed gene expression profiling (GEP; Affymetrix U133 Plus 2.0) of matched circulating peripheral PCs and bone marrow (BM) PCs from 13 patients. Whole exome sequencing (WES) was performed on purified CD138+ PCs from BM aspirates from 19 pPCL patients with a median depth of 61x. CD34+ sorted cells, taken at the time of stem cell harvest from the same 19 patients, were used as controls. Translocations and mutations were called using Manta and Strelka and annotated as previously reported. Copy number was determined by Sequenza. RESULTS/ANTICIPATED RESULTS: 1) GEP from the BM and circulating peripheral PCs showed that the expression patterns of the two samples from each individual clustered together, indicating that circulating PCs and BM PCs in pPCL result from the same clone and are biologically clearly related. 2) The clinical characteristics from the patient cohort used for WES analysis were as follows: median age was 58 years (range 36–77), females accounted for 74% (14/19), an elevated creatinine level was found in 78% (14/18) and an elevated LDH level in 71% (10/14). All patients presented with an ISS stage of III. Median OS of the whole dataset was poor at 22 months, which is consistent with OS from previously reported pPCL cohorts. 3) Primary Immunoglobulin translocations were common and identified in 63% (12/19) of patients, including MAF translocations, which are known to carry high risk in 42% (8/19) of patients [t(14;16), 32% and t(14;20), 10%] followed by t(11;14) (16%) and t(4;14) (10%). Furthermore, 32% (6/19) of patients had at least one MYC translocation, which are known to play a crucial role in disease progression. 4) The mutational burden of pPCL consisted of a median of 98 non-silent mutations per sample, suggesting that the mutational landscape of pPCL is highly complex and harbors more coding mutations than non-pPCL MM. 5) Driver mutations, that previously have been described in non-pPCL MM showed a different prevalence and distribution in pPCL, including KRAS and TP53 with 47% (9/19) and 37% (7/19) affected patients respectively compared to 21% and 5% in non-PCL MM. PIK3CA (5%), PRDM1 (10%), EP300 (10%) and NF1 (10%) were also enriched in the pPCL group compared to previously reported cases in non-pPCL MM. 6) Biallelic inactivation of TP53 – a feature of Double Hit myeloma - was found in 6/19 (32%) samples, indicating a predominance of high risk genomic features compared to non-pPCL MM. Furthermore, analysis of mutational signatures in pPCL showed that aberrant APOBEC activity was highly prevalent only in patients with a MAF translocation, but not in other translocation groups. DISCUSSION/SIGNIFICANCE OF IMPACT: In conclusion we present one of the first WES datasets on pPCL with the largest patient cohort reported to date and show that pPCL is a highly complex disease. The aggressive disease behavior can, at least in part, be explained by a high prevalence of MAF and MYC translocations, TP53 and KRAS mutations as well as bi-allelic inactivation of TP53. It is of interest that only KRAS but not NRAS mutations are highly enriched in pPCL. From all highly prevalent genomic alterations in pPCL, only KRAS mutations offer a potential for already available therapeutically targeting with MEK inhibitors, which should be further explored.
Among adults in the US, bipolar disorder affects 2.6% or 5.7 million individuals; 83% of cases are considered to be severe. Even when an accurate diagnosis of bipolar disorder is established, its treatment remains suboptimal, and those with the disorder often fail to receive any care or evidence‐based care.
A continuing medical education (CME)-certified 25-item, multiple choice clinical practice assessment survey was developed to assess recognition and treatment of bipolar disorder, specifically, the use of LAIs in these patients.
The survey included knowledge- and case-based multiple-choice questions completed confidentially online. The survey was launched on December 20, 2017 and hosted on the Medscape Education website. Participant responses were collected through January 31, 2018. Confidentiality was maintained, and responses were de-identified and aggregated before analyses.
(n=1123 psychiatrists; 305 primary care physicians [PCPs]):
- When asked about assessment tools in bipolar disorder, only 43% of psychiatrists and 36% of PCPs could identify the correct use of the MDQ screening instrument, while only 64% of psychiatrists and 51% of PCPs knew that the use of the MDQ can improve recognition of bipolar disorder in patients with depression;
- Psychiatrists were more likely to correctly identify the symptoms that most strongly support a diagnosis of bipolar disorder compared to PCPs (76% vs 43%, respectively);
- When asked about laboratory testing in mood disorders, 52% of psychiatrists and 46% of PCPs knew that laboratory testing can help exclude alternative causes for mood symptoms;
- The majority of both healthcare professionals (73%–75%) did not know that diagnosis of bipolar I disorder relies heavily on changes in activity, energy, and mood;
- 87% of psychiatrists and 76% of PCPs did not identify oral aripiprazole as the only SGA not approved by the FDA for the maintenance treatment of bipolar I disorder;
- 49% of PCPs did not recognize lithium as the first choice for maintenance monotherapy for bipolar I disorder according to the guidelines;
- Only 19% of psychiatrists and 20% of PCPs correctly chose aripiprazole monohydrate and risperidone microspheres as the LAI SGAs indicated for use as monotherapy for patients with bipolar I disorder;
- When asked what is the most common barrier to prescribing LAI antipsychotics in patients with bipolar disorder, 34% of psychiatrists selected “Patients fear of injectables”
This educational research identified psychiatrists and PCPs’ current real-world clinical practices and gaps in the knowledge and competence in the diagnosis and assessment of bipolar disorder, and the treatment options for this condition. Further educational efforts tailored to address identified gaps for each audience are warranted.
To directly observe healthcare workers in a nursing home setting to measure frequency and duration of resident contact and infection prevention behavior as a factor of isolation practice
SETTING AND PARTICIPANTS
Healthcare workers in 8 VA nursing homes in Florida, Maryland, Massachusetts, Michigan, Washington, and Texas
Over a 15-month period, trained research staff without clinical responsibilities on the units observed nursing home resident room activity for 15–30-minute intervals. Observers recorded time of entry and exit, isolation status, visitor type (staff, visitor, etc), hand hygiene, use of gloves and gowns, and activities performed in the room when visible.
A total of 999 hours of observation were conducted across 8 VA nursing homes during which 4,325 visits were observed. Residents in isolation received an average of 4.73 visits per hour of observation compared with 4.21 for nonisolation residents (P<.01), a 12.4% increase in visits for residents in isolation. Residents in isolation received an average of 3.53 resident care activities per hour of observation, compared with 2.46 for residents not in isolation (P<.01). For residents in isolation, compliance was 34% for gowns and 58% for gloves. Healthcare worker hand hygiene compliance was 45% versus 44% (P=.79) on entry and 66% versus 55% (P<.01) on exit for isolation and nonisolation rooms, respectively.
Healthcare workers visited residents in isolation more frequently, likely because they required greater assistance. Compliance with gowns and gloves for isolation was limited in the nursing home setting. Adherence to hand hygiene also was less than optimal, regardless of isolation status of residents.
We sought to evaluate the first-in-man use of a new system for implantation of covered stents in patients with complex structural and CHD.
Methods and results
Retrospective data were collected of the first 13 NuDEL™ delivery systems used in patients. The NuDEL™ comprises a covered Cheatham-Platinum stent mounted on a balloon-in-balloon and pre-loaded in a long delivery sheath. Data were collected from three centres in the United Kingdom and Ireland. A total of 13 covered stents were delivered via 12 NuDEL™ delivery systems in 12 patients. Among them, six patients had coarctation of the aorta, five patients had right ventricular outflow tract stenosis, and one patient had severe stenosis of a Mustard systemic venous baffle. There were no complications, and all the stents were deployed in the desired position with satisfactory haemodynamic results.
The development of a bespoke system of a pre-mounted, pre-loaded covered stent may negate some of the technical challenges that complicate large-calibre stent deployment. Our preliminary results suggest that the NuDEL™ system is a safe and effective means of covered stent deployment in challenging anatomy.
This study aimed to review available disaster training options for health care providers, and to provide specific recommendations for developing and delivering a disaster-response-training program for non-disaster-trained emergency physicians, residents, and trainees prior to acute deployment.
A comprehensive review of the peer-reviewed and grey literature of the existing training options for health care providers was conducted to provide specific recommendations.
A comprehensive search of the Pubmed, Embase, Web of Science, Scopus, and Cochrane databases was performed to identify publications related to courses for disaster preparedness and response training for health care professionals. This search revealed 7,681 unique titles, of which 53 articles were included in the full review. A total of 384 courses were found through the grey literature search, and many of these were available online for no charge and could be completed in less than six hours. The majority of courses focused on management and disaster planning; few focused on clinical care and acute response.
There is need for a course that is targeted toward emergency physicians and trainees without formal disaster training. This course should be available online and should utilize a mix of educational modalities, including lectures, scenarios, and virtual simulations. An ideal course should focus on disaster preparedness, and the clinical and non-clinical aspects of response, with a focus on an all-hazards approach, including both terrorism-related and environmental disasters.
HansotiB, KelloggDS, AberleSJ, BroccoliMC, FedenJ, FrenchA, LittleCM, MooreB, SabatoJJr., SheetsT, WeinbergR, ElmesP, KangC. Preparing Emergency Physicians for Acute Disaster Response: A Review of Current Training Opportunities in the US. Prehosp Disaster Med. 2016;31(6):643–647.