To save 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 saving content to .
To save 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 saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved 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.
With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist.
HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions?
This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected.
This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.
As COVID-19 was declared a health emergency in March 2020, there was immense demand for information about the novel pathogen. This paper examines the clinician-reported impact of Project ECHO COVID-19 Clinical Rounds on clinician learning. Primary sources of study data were Continuing Medical Education (CME) Surveys for each session from the dates of March 24, 2020 to July 30, 2020 and impact surveys conducted in November 2020, which sought to understand participants’ overall assessment of sessions. Quantitative analyses included descriptive statistics and Mann-Whitney testing. Qualitative data were analyzed through inductive thematic analysis. Clinicians rated their knowledge after each session as significantly higher than before that session. 75.8% of clinicians reported they would ‘definitely’ or ‘probably’ use content gleaned from each attended session and clinicians reported specific clinical and operational changes made as a direct result of sessions. 94.6% of respondents reported that COVID-19 Clinical Rounds helped them provide better care to patients. 89% of respondents indicated they ‘strongly agree’ that they would join ECHO calls again.COVID-19 Clinical Rounds offers a promising model for the establishment of dynamic peer-to-peer tele-mentoring communities for low or no-notice response where scientifically tested or clinically verified practice evidence is limited.
Burn patients are particularly vulnerable to infection, and an estimated half of all burn deaths are due to infections. This study explored risk factors for healthcare-associated infections (HAIs) in adult burn patients.
Retrospective cohort study.
Tertiary-care burn center.
Adults (≥18 years old) admitted with burn injury for at least 2 days between 2004 and 2013.
HAIs were determined in real-time by infection preventionists using Centers for Disease Control and Prevention criteria. Multivariable Cox proportional hazards regression was used to estimate the direct effect of each risk factor on time to HAI, with inverse probability of censor weights to address potentially informative censoring. Effect measure modification by burn size was also assessed.
Overall, 4,426 patients met inclusion criteria, and 349 (7.9%) patients had at least 1 HAI within 60 days of admission. Compared to <5% total body surface area (TBSA), patients with 5%–10% TBSA were almost 3 times as likely to acquire an HAI (hazard ratio [HR], 2.92; 95% CI, 1.63–5.23); patients with 10%–20% TBSA were >6 times as likely to acquire an HAI (HR, 6.38; 95% CI, 3.64–11.17); and patients with >20% TBSA were >10 times as likely to acquire an HAI (HR, 10.33; 95% CI, 5.74–18.60). Patients with inhalational injury were 1.5 times as likely to acquire an HAI (HR, 1.61; 95% CI, 1.17–2.22). The effect of inhalational injury (P=.09) appeared to be larger among patients with ≤20% TBSA.
Larger burns and inhalational injury were associated with increased incidence of HAIs. Future research should use these risk factors to identify potential interventions.
Background: Depression and anxiety are the two most frequently studied emotional outcomes of stroke. However, few previous studies have been carried out at a population level or beyond 6 months post stroke. The aim of this study was to describe depression and anxiety across the first year following incident ischemic stroke (IS), and identify predictive factors in a population-based study.
Method: The Hospital Anxiety Depression Scale (HADS) was administered at baseline (within 2 weeks of onset), and again at 1-month, 6-months and 12-months after IS in a sample (N = 365) drawn from a population-based study.
Results: Over 75% of those assessed experienced depression or anxiety symptoms below cut-offs for probable disorder across the year post stroke. Moderate to severe symptoms for anxiety were approximately twice as likely (range 4.1%–10.6%) as compared to depression (range 2.5%–5.0%) at each assessment. The greatest improvement in anxiety occurred within the first month post stroke. In contrast, the greatest reduction in depression occurred between 1- to 6-months post stroke.
Conclusions: Anxiety symptoms in the moderate to severe range were twice as common as depression, and improved over the first month post stroke, whilst depression symptoms persisted for up to 6 months, indicating a need to target these two issues at different points in the recovery process.
Ventilator-associated pneumonia (VAP) is a frequent complication of severe burn injury. Comparing the current ventilator-associated event-possible VAP definition to the pre-2013 VAP definition, we identified considerably fewer VAP cases in our burn ICU. The new definition does not capture many VAP cases that would have been reported using the pre-2013 definition.
Taphonomic processes in deep-water environments differ markedly from those in shallow waters. These differences are illustrated by the preservational style of a large cetacean skeleton lying at the bottom of the Santa Catalina Basin in 1,240 m of water. The degree of skeletal articulation contrasts with that documented in the shallow North Sea where gas-filled, buoyant carcasses disarticulated during flotation. Increased hydrostatic pressure at greater depth is presumed to have prevented the whale carcass from floating and promoted increased levels of preservation. We present a model that relates gas evolution during decay to carcass buoyancy with depth. Application of this model may ultimately allow the degree of skeletal articulation to be used as a rough index of paleobathymetry.
Our principal focus in this paper is on ways that a Fast Close process (or indeed any reserving process) can be structured to maximise the value added within the process given the time and resource available. This builds on the use of actual vs. expected techniques investigated in our previous paper, and also looks at forces external to the reserving function that may derail smooth progress. We highlight a number of practical ways that the balance can be restored in favour of adding value rather than crunching numbers. This paper forms the second in the TORP series.
Burn injuries are a common source of morbidity and mortality in the United States, with an estimated 450,000 burn injuries requiring medical treatment, 40,000 requiring hospitalization, and 3,400 deaths from burns annually in the United States. Patients with severe burns are at high risk for local and systemic infections. Furthermore, burn patients are immunosuppressed, as thermal injury results in less phagocytic activity and lymphokine production by macrophages. In recent years, multidrug-resistant (MDR) pathogens have become major contributors to morbidity and mortality in burn patients.
Since only limited data are available on the incidence of both device- and nondevice-associated healthcare-associated infections (HAIs) in burn patients, we undertook this retrospective cohort analysis of patients admitted to our burn intensive care unit (ICU) from 2008 to 2012.
Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting females almost exclusively and is characterized by a wide spectrum of clinical manifestations. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene have been found in up to 95% of classical RTT cases and a lesser proportion of atypical cases. Recently, mutations in another X-linked gene, CDKL5 (cyclin-dependent kinase-like 5) have been found to cause atypical RTT, in particular the early onset seizure (Hanefeld variant) and one female with autism. In this study we screened several cohorts of children for CDKL5 mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative for MECP2 mutations (n = 102), males with X-linked mental retardation (n = 9), patients with West syndrome (n = 52), patients with autism (n = 59), patients with epileptic encephalopathy (n = 33), patients with Aicardi syndrome (n = 7) and other patients with intellectual disability with or without seizures (n = 54). In all, seven polymorphic variations and four de novo mutations (c.586C>T [p.S196L]; c.58G>C [p.G20R]; c.2504delC [p.P835fs]; deletion of exons 1 - 3) were identified, and in all instances of the latter the clinical phenotype was that of an epileptic encephalopathy. These results suggest that pathogenic CDKL5 mutations are unlikely to be identified in the absence of severe early-onset seizures and highlight the importance of screening for large intragenic and whole gene deletions.
Cognitive reserve is thought to reflect life experiences. Which experiences contribute to reserve and their relative importance is not understood. Subjects were 652 autopsied cases from the Rush Memory and Aging Project and the Religious Orders Study. Reserve was defined as the residual variance of the regressions of cognitive factors on brain pathology and was captured in a latent variable that was regressed on potential determinants of reserve. Neuropathology variables included Alzheimer's disease markers, Lewy bodies, infarcts, microinfarcts, and brain weight. Cognition was measured with six cognitive domain scores. Determinants of reserve were socioeconomic status (SES), education, leisure cognitive activities at age 40 (CA40) and at study enrollment (CAbaseline) in late life. The four exogenous predictors of reserve were weakly to moderately inter-correlated. In a multivariate model, all except SES had statistically significant effects on Reserve, the strongest of which were CA40 (β = .31) and CAbaseline (β = .28). The Education effect was negative in the full model (β = –.25). Results suggest that leisure cognitive activities throughout adulthood are more important than education in determining reserve. Discrepancies between cognitive activity and education may be informative in estimating late life reserve. (JINS, 2011, 17, 615–624)
Studies of neuropathology-cognition associations are not common and have been limited by small sample sizes, long intervals between autopsy and cognitive testing, and lack of breadth of neuropathology and cognition variables. This study examined domain-specific effects of common neuropathologies on cognition using data (N = 652) from two large cohort studies of older adults. We first identified dimensions of a battery of 17 neuropsychological tests, and regional measures of Alzheimer’s disease (AD) neuropathology. We then evaluated how cognitive factors were related to dimensions of AD and additional measures of cerebrovascular and Lewy Body disease, and also examined independent effects of brain weight. All cognitive domains had multiple neuropathology determinants that differed by domain. Neocortical neurofibrillary tangles were the strongest predictors of most domains, while medial temporal tangles showed a weaker relationship with episodic memory. Neuritic plaques had relatively strong effects on multiple domains. Lewy bodies and macroscopic infarcts were associated with all domains, while microscopic infarcts had more limited associations. Brain weight was related to all domains independent of specific neuropathologies. Results show that cognition is complexly determined by multiple disease substrates. Neuropathological variables and brain weight contributed approximately a third to half of the explained variance in different cognitive domains. (JINS, 2011, 17, 602–614).
Short stories are written by individuals but they are influenced by other writers, critics and publishers. More than other literary genres, short stories are dependent on newspapers and magazines or anthologies for first publication. The literary activity of short story writers may therefore be represented as an individual struggling for self-expression, but a more comprehensive and realistic view includes writers, editors, publishers and readers in a continual process of interaction – each adjusting or readjusting their role in relation to the others’ needs and requirements. This interactive process may affect the length of stories, whether they entertain or instruct, and their shape or form.
This chapter will give most attention to individual short story writers and collections of their work from the 1890s to about 1950 in their literary, geographic and historical contexts. Special attention will also be given to newspapers and periodical publications as well as books, and responses to them by readers and critics. Questions of evaluation arise. For instance, can any Australian writer of short stories between the 1890s and 1950 be called ‘great’? A combination of favourable critical responses, contemporary popularity and sustained attention by publishers over time would place Henry Lawson in this category. But what does such categorisation mean? In particular, how are such qualitative judgments to be distinguished from commercial considerations? An example is the case of Steele Rudd, whose successful marketing and transmutations of his Dad and Dave stories into plays and films extended his reach beyond Lawson’s.
The recessive lethal T/t-complex haplotype tw75 was isolated from Jena, East Germany, prior to 1973. It was at first thought to be a standard member of the tw5 complementation group because matings of T/tw75 × T/tw5 produced tailless offspring only (Dunn, Bennett & Cookingham, 1973). Cross tests with all other complementation groups and embryological studies have recently been completed, with results demonstrating that tw75 does not complement the members of either the tw5 or the tw1 complementation groups. Histological studies show that compound embryos tw75/tw5 and tw75/tw1 die with symptoms indistinguishable from tw5/tw5 and tw1/tw1 homozygtes respectively. Thus tw75 represents the first confirmed isolation of a t-haplotype that overlaps two complementation groups.
Matings between mice bearing the dominant deletion Thp and mice segregating for the tw73 haplotype failed to produce the expected viable tailless (Thp/tw73) progeny. Histological analysis of litters from Thp / + × + /tw73 matings revealed an abnormal class of embryos which failed to implant normally between days 6·5 and 7·5 of gestation, and were indistinguishable from tw73/tw73 homozygotes. Thp homozygotes displayed a different lethal phenotype, failing to successfully make the transition from morula to blastocyst at day 3·5. These studies indicate that the mutation responsible for the tw73 implantation defect maps within the Thp deletion. Since tw73 is viable with another deletion, Torl, the tw73 defect must occur in the region of non-overlap between Thp and TOrl. The possibility that the tw73-associated implantation defect is a parasitic lethal mutation (p), mapping to the proximal part of the tw73 chromosome, is discussed.
A strong correlation exists between the Li isotopic compositions of CarboniferousTriassic granites from the New England Batholith, and the previously inferred involvement of sedimentary and mantle/infracrustal source components. Isotopically (Nd and Sr) juvenile, low-K, Cordilleran I-type granites of the Clarence River supersuite have δ7 Li= +2·2 to +8‰ similar to those of arc magmas, the inferred source of these granites (Bryant et al. 1997). Isotopic variability within this supersuite probably arises from heterogeneity within primary mantle-derived magmas, combined with subsequent modifications through interactions with crustal materials. Oxidised, high-K granites of the Moonbi Supersuite have more homogenous and slightly lighter Li isotopic compositions (δ7 Li= +1·9 to +4·2‰). The observed range of values lies within the range of arc magmas, and is consistent with partial melting of arc shoshonites within the crust (cf. Chappell 1978) or the involvement of high-K mantle-derived magmas (cf. Shaw & Flood 1981; Landenberger & Collins 1998). S-type granites of the Bundarra (δ7 Li= −0·1 to +2·1‰; average= +1˙3‰; n=6) and Hillgrove supersuites (δ7 Li= +0·4 to +1·7‰; average= +0·8‰) define a narrow range of isotopic compositions which are, overall, lower than those observed in NEB I-type granites or generally observed in primary arc magmas. Their isotopic compositions are equivalent to those typically observed in shales (primarily δ7 Li= −3·2 to +2·0‰; Moriguti & Nakamura 1998; Teng et al. 2004). No difference is evident in the isotopic compositions of the two S-type supersuites despite inferred differences in the degree of weathering experienced by the sedimentary protolith, or differences in mineralogy of the granites. Granites of the Uralla Supersuite, which have been have formed from mixtures of local meta-igneous and meta-sedimentary components, span a broad range of values (δ7 Li= −1·3 to +3·9‰) which overlap with both the sediment-poor New England Batholith I-type intrusions of the Clarence River and Moonbi supersuites, and the S-type granites of the Bundarra and Hillgrove supersuites. Lower δ7 Li values primarily occur in lower-K plutons from the northern portion of the Uralla Supersuite.
Overall, anatexis and magma differentiation do not appear to contribute to significant fractionation of Li isotopes relative to the inferred source components. However, subtly lower δ7 Li values, evident in the three leucogranites analysed herein, imply that subtle Li isotopic fractionation may occur in association with the exsolution of an aqueous fluid. Like most isotopic systems, the Li isotopic composition of rocks is not a definitive guide to source rock compositions, but given the results herein, the present authors suggest that it may play a very useful role in understanding crustal processes.