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.
Presenteeism, or working while ill, by healthcare personnel (HCP) experiencing influenza-like illness (ILI) puts patients and coworkers at risk. However, hospital policies and practices may not consistently facilitate HCP staying home when ill.
Objective and methods:
We conducted a mixed-methods survey in March 2018 of Emerging Infections Network infectious diseases physicians, describing institutional experiences with and policies for HCP working with ILI.
Of 715 physicians, 367 (51%) responded. Of 367, 135 (37%) were unaware of institutional policies. Of the remaining 232 respondents, 206 (89%) reported institutional policies regarding work restrictions for HCP with influenza or ILI, but only 145 (63%) said these were communicated at least annually. More than half of respondents (124, 53%) reported that adherence to work restrictions was not monitored or enforced. Work restrictions were most often not perceived to be enforced for physicians-in-training and attending physicians. Nearly all (223, 96%) reported that their facility tracked laboratory-confirmed influenza (LCI) in patients; 85 (37%) reported tracking ILI. For employees, 109 (47%) reported tracking of LCI and 53 (23%) reported tracking ILI. For independent physicians, not employed by the facility, 30 (13%) reported tracking LCI and 11 (5%) ILI.
More than one-third of respondents were unaware of whether their institutions had policies to prevent HCP with ILI from working; among those with knowledge of institutional policies, dissemination, monitoring, and enforcement of these policies was highly variable. Improving communication about work-restriction policies, as well as monitoring and enforcement, may help prevent the spread of infections from HCP to patients.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
To describe the use of balloon dilation with non-invasive ventilation in the treatment of pregnant patients with idiopathic subglottic stenosis.
The medical charts of four consecutive patients who underwent jet ventilation or high-flow nasal cannula oxygenation with balloon dilation for the treatment of idiopathic subglottic stenosis during pregnancy were reviewed.
Objective improvement of subglottic stenosis was seen in all four cases, with end-result Myer–Cotton grade 1 lesions down from pre-procedure grade 3 lesions. Patients also reported subjective improvements in symptomatology, with no further airway issues. All patients delivered normally, at term.
Laryngeal dilation with continuous radial expansion pulmonary balloons using non-invasive ventilation for the treatment of idiopathic subglottic stenosis in pregnant patients is safe and efficacious, and should be the first line treatment option for this patient population. The improvement in symptoms, and lack of labour and pregnancy complications, distinguish this method of treatment from others reported in the literature.
Every four years leading researchers gather to survey the latest developments in all aspects of group theory. Initially held in St Andrews, these meetings have become the premier forum for group theory across the whole of the UK. Since 1981, the proceedings of 'Groups St Andrews' have provided a regular snapshot of the state-of-the-art in group theory and helped to shape the direction of research in the field. This volume contains papers from the 2017 meeting held in Birmingham. It includes expository articles from the invited speakers, and further surveys contributed by the participants. Topics include: generation of finite simple groups, block theory, fusion systems, algebraic groups, one-relator groups, geometric group theory, and Beauville groups.
OBJECTIVES/SPECIFIC AIMS: The primary goal of the project was to conduct a narrative review of the published literature to identify and summarize best practices for developing oncology-focused research and training experiences for AI/AN undergraduate, graduate and professional students. A secondary goal was to identify methodological limitations and areas for future research related to rigorous educational program evaluation. METHODS/STUDY POPULATION:. Published literature was searched using databases relevant to oncology (PubMed, Web of Science) and sociology (PsychINFO, SocIndex). The bibliographies of identified relevant papers were searched for additional references by title. Search terms included synonyms and commonly used terms for three general areas: (1) target population (e.g., American Indian), (2) training area (e.g., oncology), and (3) educational program (e.g., undergraduate). RESULTS/ANTICIPATED RESULTS:. A current total of 107 original publications and 33 review papers that are relevant to the project goals have been identified. Key areas of program development and implementation relate to advertising and recruitment; didactic curriculum in research methods, cancer health disparities, and professional development and career planning; research immersion experiences through shadowing, networking, application of research skills, and opportunities to develop oral and written communication skills; ongoing career development support; mentoring by faculty, advanced trainees, and peers; and culture-specific enrichment. Important areas for program evaluation relate to measures of reaction, knowledge, practice and long-term outcomes. Evaluation design approaches include observational and experimental designs with recommendations for identifying relevant control groups. Strategies to ensure complete long-term follow-up are also summarized. DISCUSSION/SIGNIFICANCE OF IMPACT:.Successful programs address barriers related to perceived lack of abilities, lack of AI role models, limited culture-specific enrichment, and limited mentoring and ongoing career development support. Program directors should work with local tribal and community leaders when creating a new program. A high degree of coordination is needed to create a bicultural program to interest students in a research career and avoid the creation of barriers hidden to the program director. There are opportunities to improve the rigor of educational program evaluation in this setting by including measures beyond self-reported reaction and knowledge to focus on educational program enrollment and completion and long-term career outcomes. Methodologic challenges include identification of relevant control groups for comparison and the use of experimental designs.
The Glasgow area has a combination of highly variable superficial deposits and a legacy of heavy industry, quarrying and mining. These factors create complex foundation and hydrological conditions, influencing the movement of contaminants through the subsurface and giving rise locally to unstable ground conditions. Digital geological three-dimensional models developed by the British Geological Survey are helping to resolve the complex geology underlying Glasgow, providing a key tool for planning and environmental management. The models, covering an area of 3200km2 to a depth of 1.2km, include glacial and post-glacial deposits and the underlying, faulted Carboniferous igneous and sedimentary rocks. Control data, including 95,000 boreholes, digital mine plans and published geological maps, were used in model development. Digital outputs from the models include maps of depth to key horizons, such as rockhead or depth to mine workings. The models have formed the basis for the development of site-scale high-resolution geological models and provide input data for a wide range of other applications from groundwater modelling to stochastic lithological modelling.
Background: Congenital Myasthenic Syndromes (CMS) are heterogeneous disorders caused by genetically determined structural or functional differences in proteins involved with the neuromuscular junctions. Clinical and molecular genetics studies of CMS patients have revealed significant locus heterogeneity; there are 21 known genes related to CMS, but other genes may mimic the phenotype, justifying the use of a multi-gene panel for genetic testing Methods: Our group developed custom sequence capture probes designed to flank 27 different genes associated with CMS, including enrichment for all coding exons as well the flanking intronic regions. We enrolled 20 patients from the paediatric and adult neuromuscular clinic with a clinical phenotype of CMS. Using custom analytical, we -assessed the sequence variants and exon-level CNVs for each patient. Results: Thirteen male and seven female patients with median age of 12.25 years (range 1.5-39y) were assessed. We identified missense and CNVs in 17 patients, including established pathogenic mutations confirming the diagnosis in 5 patients Conclusions: The use of Next Generation Sequence with CNV for CMS can help determine the underlying causes of most CMS disorders and allow appropriate medical treatment, refined genetic counseling, and improved understanding of prognosis, justifying the implementation in the standard clinical screening of CMS.
OBJECTIVES/SPECIFIC AIMS: The overall goal of this project is to enhance the use of GCRA in Latina breast cancer survivors at high risk of hereditary breast and ovarian cancer to reduce disparities in GCRA uptake. The aims of the study are to (1) develop a cultural adaptation of an evidence-based TGC intervention that consists of phone genetic counseling and a booklet, (2) evaluate the impact of TGC Versus Usual Care, and (3) explore the communication patterns in TGC and genetic counseling sessions with an interpreter. METHODS/STUDY POPULATION: We are conducting a 2-phase, mixed methods study. In Phase I we will develop a cultural adaption of an evidence-based intervention (TGC) for high-risk Latina breast cancer survivors using the Learner Verification and Revision Framework (n=15). In Phase II we will use a cluster randomized design with four community sites randomized to Spanish TGC (n=2 sites) or usual care (n=2 sites) (n=60; 15 per site). The primary outcome is genetic counseling uptake. Among women who receive genetic counseling either through TGC (n~30) or with an interpreter (n~15), we will assess counseling quality by reviewing 20 randomly selected audiotaped sessions (10 TGC; 10 interpreters). We will evaluate women’s HBOC knowledge and satisfaction with counseling. Communication processes and outcomes will be assessed using gold standard RIAS quantitative coding system and qualitative discourse analysis. RESULTS/ANTICIPATED RESULTS: We elicited input from transdisciplinary team members to develop an initial adaptation of a TGC print booklet and intervention protocol for use with high-risk Latina breast cancer survivors with limited English proficiency. The booklet contains low-literacy information about HBOC, risk factors, pros and cons of testing, and management strategies. Based on these materials and prior work, we anticipate TGC will consist of one 1 hour or less TGC session by phone. Participants interested in pursuing testing will receive a saliva kit and will participate in a second TGC session (30 min) to discuss test results and management options. DISCUSSION/SIGNIFICANCE OF IMPACT: Given access barriers and the shortage of Spanish-speaking genetic counselors, adapting and translating TGC intervention is a promising strategy that could reduce disparities by broadening the reach and accessibility to genetic counseling while enhancing the quality of the service for Latinas with limited English proficiency.
Background: When measuring young Duchenne Muscular Dystrophy (DMD) patients’ health-related quality of life (HRQoL), parent-proxy reports are heavily relied on. Therefore, it is imperative that the relationship between parent-proxy and child self-report HRQoL is understood. This study examined the level of agreement between children and their parent-proxy rating of the child’s HRQoL. Methods: We used FOR-DMD clinical trial baseline data. HRQoL, measured using the PedsQL inventory, was reported by 178 parent and child (ages 4 to 7 years) dyads. Intracorrelation coefficients (ICC) measured absolute agreement while paired t-tests determined differences in the average HRQoL ratings between groups. Results: The level of agreement between child and parent-proxy ratings of HRQoL was poor for the generic PedsQL scale (ICC: 0.29) and its subscales; and, similarly low for the neuromuscular disease module (ICC:0.16). On average, parents rated their child’s HRQoL as poorer than the children rated themselves in all scales except for psychosocial and school functioning. Conclusions: Child and parent-proxy HRQoL ratings are discordant in this study sample, as occurs in other chronic pediatric diseases. This should be taken into account when interpreting clinical and research HRQoL findings in this population. Future studies should examine reasons for parents’ perception of poorer HRQoL than that reported by their children.
Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. In June 2017, Health Canada approved Nusinersen, currently the only available drug for SMA. Since 2016, patients in Ontario have been treated clinically with Nusinersen through different access programs. Methods: Retrospective case series of patients with SMA treated clinically with Nusinersen in Ontario, describing clinical characteristics and logistics of intrathecal Nusinersen administration. Results: Twenty patients have been treated across four centres. To date, we have reviewed 8 cases at one centre (seven SMA Type I, one SMA Type II). Age at first dose ranged from 3-156 months and disease duration 9-166 months. Patients had received 4-7 doses at last evaluation. Three patients with scoliosis (2 with spinal rods) required fluoroscopy-guided radiologist administration, and 4 required general anesthesia. No complications/adverse events were reported. At last follow up, 5/8 families reported improved daily activities. Of 5 patients with baseline and follow up motor function testing, 3 demonstrated improved scores. One patient died due to respiratory decline at age 9 months, despite improved motor outcome scores. Conclusions: We describe the first Canadian post-marketing experience with Nusinersen. Timely dissemination of this information is needed to guide clinicians, hospital administrators, and policy-makers.
Background: The goal was to understand factors leading to prolonged wait times for neurological assessment of children with new onset seizures. A second objective was to develop an innovative approach to patient flow through and achieve a reduction in waiting times utilizing limited resources.
Audit of the referrals, flow through, wait times
Identification of bottlenecks
Development of triaging strategy:
Suspected Febrile seizures and non-epileptic events;
Suspected benign and absence epilepsies;
Suspected other Focal epilepsies, generalized epilepsies, epilepsy under 2 years
Initiation of early telephone contact and support
Development of a ketogenic diet
Results: Using a triaging strategy and focusing on timely access to investigations, wait times for clinic evaluations were shortened despite larger numbers of referrals (mean wait time reductions from 179 to 91 days). Limiting factors such increase in referral numbers, attrition in support staff, interfered with sustainability of reduced wait times achieved in the initial phase of the program. Conclusions: This pilot study highlights the effectiveness of an innovative triaging strategy and improvements in patient flow through in achieving the goals of reduction in wait times for clinical evaluation and timely investigations to improve care for children with new onset seizures. Insights into limitations of such strategies and factors determining sustainability are discussed.
Auctions have been used for more than 2,500 years to allocate a single indivisible asset. They are also used to sell multiple units of some commodities, such as rare wine or a new crop of tulip bulbs. There are many different types of auctions in use, and far more that have never been tried but could be employed if we felt that they served some purpose. The aim of this chapter is to determine which type of auction should be used in a particular situation. Accordingly, we need to determine which bidder would get the asset that is up for sale and then howmuch would be paid for it.
When the government sells things at auction – treasury bills, oil-drilling rights, or a TV broadcast frequency, for instance – the appropriate criterion for determining which type of auction should be used is the maximization of general consumer welfare. Because the bidders are usually firms, we recommend the auction type that would put the asset in the hands of the firm that would use it to produce the highest level of consumer welfare. Fortunately, this is correlated with the value of the asset to a bidder: the more valuable the asset is to consumers when it is used by firm X, themore profit X anticipates from owning the asset, and thus the higher the value that X itself places on the asset. (Section 6.1.2 explains why revenue net of cost is a good measure of the benefit that consumers derive from a firm's activities.) The discounted stream of profits that would flow from the asset is the individual firm's reservation value, and it is a hidden characteristic. If the government were to ask each firm to report its reservation value and awarded the asset to the high-value firm it would get nothing resembling truthful revelation. Each would have a strong incentive to overstate the value it places on the asset in an attempt to increase the probability of being awarded the asset.