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Objectives/Goals: The timing of neurosurgery is highly variable for post-hemorrhagic hydrocephalus (PHH) of prematurity. We sought to utilize microvascular imaging (MVI) in ultrasound (US) to identify biomarkers to discern the opportune time for intervention and to analyze the cerebrospinal fluid (CSF) characteristics as they pertain to neurosurgical outcome. Methods/Study Population: The inclusion criteria for the study are admission to the neonatal intensive care unit (NICU) with a diagnosis of Papile grade III or IV. Exclusion criteria are congenital hydrocephalus and hydrocephalus secondary to myelomeningocele/brain tumor/vascular malformation. We are a level IV tertiary referral center. Our current clinical care pathway utilizes brain US at admission and at weekly intervals. Patients who meet certain clinical and radiographic parameters undergo temporary or permanent CSF diversion. Results/Anticipated Results: NEL was implemented at our institution for PHH of prematurity in fall 2022. To date, we have had 20 patients who were diagnosed with grade III or IV IVH, of which 12 qualified for NEL. Our preliminary safety and feasibility results as well as the innovative bedside technique pioneered at our institution are currently in revision stages for publication. Preliminary results of the MVI data have yielded that hyperemia may confer venous congestion in the germinal matrix, which should then alert the neurosurgeon to delay any intervention to avoid progression of intraventricular blood. With regard to CSF characteristics, we anticipate that protein, cell count, hemoglobin, iron, and ferritin will decrease with NEL. Discussion/Significance of Impact: The timing of PHH of prematurity is highly variable. We expect that MVI will offer radiographic biomarkers to guide optimal timing of neurosurgical intervention. A better understanding of CSF characteristics could potentially educate the neurosurgeon with regard to optimal timing of permanent CSF diversion based on specific CSF parameters.
The intraclass correlation, ρ, is a parameter featured in much psychological research. Two commonly used estimators of ρ, the maximum likelihood and least squares estimators, are known to be negatively biased. Olkin and Pratt (1958) derived the minimum variance unbiased estimator of the intraclass correlation, but use of this estimator has apparently been impeded by the lack of a closed form solution. This note briefly reviews the unbiased estimator and gives a FORTRAN 77 subroutine to calculate it.
Weight loss results in obligatory reductions in energy expenditure (EE) due to loss of metabolically active fat-free mass (FFM). This is accompanied by adaptive reductions (i.e. adaptive thermogenesis) designed to restore energy balance while in an energy crisis. While the ‘3500-kcal rule’ is used to advise weight loss in clinical practice, the assumption that EE remains constant during energy restriction results in a large overestimation of weight loss. Thus, this work proposes a novel method of weight-loss prediction to more accurately account for the dynamic trajectory of EE. A mathematical model of weight loss was developed using ordinary differential equations relying on simple self-reported inputs of weight and energy intake to predict weight loss over a specified time. The model subdivides total daily EE into resting EE, physical activity EE, and diet-induced thermogenesis, modelling obligatory and adaptive changes in each compartment independently. The proposed model was tested and refined using commercial weight-loss data from participants enrolled on a very low-energy total-diet replacement programme (LighterLife UK, Essex). Mathematical modelling predicted post-intervention weight loss within 0.75% (1.07 kg) of that observed in females with overweight or obesity. Short-term weight loss was consistently underestimated, likely due to considerable FFM reductions reported on the onset of weight loss. The best model agreement was observed from 6 to 9 weeks where the predicted end-weight was within 0.35 kg of that observed. The proposed mathematical model simulated rapid weight loss with reasonable accuracy. Incorporated terms for energy partitioning and adaptive thermogenesis allow us to easily account for dynamic changes in EE, supporting the potential use of such a model in clinical practice.
Can the best arguments for a privation theory of evil be parodied, with equal plausibility, as arguments for a privation theory of good? The privation theory of evil claims that evil has no positive existence, and it is but a privation of good. The privation theory of good claims the opposite. I approach this topic as one element in the so-called evil-God Challenge. Stephen Law has argued that the epistemic support for belief in an omniscient, omnipotent, and morally perfect God (theism) is on a par with the epistemic support for belief in an omniscient, omnipotent, but completely evil-God (maltheism). In fact, he concludes, the arguments for an evil God are symmetrical with, and isomorphic to, those for a good God. The privation theory of evil has often been used to defend theism against the argument from evil. Thus, part of the evil-God Challenge is to evaluate arguments for the privation theory of evil for their vulnerability to maltheist parody. I consider a broad range of arguments for the privation theory of evil, and I argue that most of them are vulnerable to parodic neutralization. Furthermore, I argue that although the thesis of the convertibility of being and goodness is often held to entail the privation theory of evil, or to be entailed by it (or to be equivalent to it), it is independent of the privation theory. I do find that David Oderberg’s recent argument for the privation theory of evil resists any easy maltheist parody, but I argue that it has a defect. I sketch an argument according to which his good-as-fulfillment account is compatible with a perfectly evil god. My tentative conclusion is that the privation theory of evil enjoys little more plausibility than does the privation theory of good.
Jellyfishes have ecological and societal value, but our understanding of taxonomic identity of many jellyfish species remains limited. Here, an approach integrating morphological and molecular (16S ribosomal RNA and cytochrome oxidase I) data enables taxonomic assessment of the blubber jellyfish found in the Philippines. In this study, we aimed to resolve doubt on the taxonomy of Acromitoides purpurus, a valid binomen at the time of our research. Our morphological findings confirm that this jellyfish belongs to the genus Catostylus, and is distinct from known species of the genus inhabiting the Western Pacific, such as Catostylus ouwensi, Catostylus townsendi, and Catostylus mosaicus. Detailed morphological and molecular analyses of the type specimens from the Philippines with the other Catostylus species revive the binomen Catostylus purpurus and invalidate A. purpurus. Genetic analysis also distinguishes this Philippine jellyfish from C. townsendi and C. mosaicus. Through this study, we arranged several Catostylidae taxa into species inquirendae (Catostylus tripterus, Catostylus turgescens, and Acromitoides stiphropterus) and one genus inquirenda (Acromitoides) and provided an identification key for species of Catostylus. This comprehensive study confirms the blubber jellyfish as C. purpurus, enriching our understanding of jellyfish biodiversity. The integration of morphological and genetic analyses proves vital in resolving taxonomic ambiguities within the Catostylidae family and in the accurate identification of scyphozoan jellyfishes.
Rapid Acceleration of Diagnostics (RADx®) Tech was the key diagnostics component of a three-pronged national strategy, including vaccines and therapeutics, to respond to the COVID-19 pandemic. Unprecedented in the scale of its mission, its budget, its accelerated time frame, the extent of cross-government agency collaboration and information exchange, and the blending of business, academic, and investment best practices, RAD Tech successfully launched dozens of US Food and Drug Administration Emergency Use Authorization diagnostic tests, established a new model for rapidly translating diagnostic tests from the laboratory to the marketplace, and accelerated public acceptance of home-based diagnostic tests. This chapter provides an overview of the processes utilized by RADx Tech during the COVID-19 pandemic to improve clinical laboratory tests and identify, evaluate, support, validate, and commercialize innovative point-of-care and home-based tests that directly detected the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus.
Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother–infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.
To describe national antibiotic prescribing for acute gastroenteritis (AGE).
Setting:
Ambulatory care.
Methods:
We included visits with diagnoses for bacterial and viral gastrointestinal infections from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS; 2006–2015) and the IBM Watson 2014 MarketScan Commercial Claims and Encounters Database. For NAMCS/NHAMCS, we calculated annual percentage estimates and 99% confidence intervals (CIs) of visits with antibiotics prescribed; sample sizes were too small to calculate estimates by pathogen. For MarketScan, we used Poisson regression to calculate the percentage of visits with antibiotics prescribed and 95% CIs, including by pathogen.
Results:
We included 10,210 NAMCS/NHAMCS AGE visits; an estimated 13.3% (99% CI, 11.2%–15.4%) resulted in antibiotic prescriptions, most frequently fluoroquinolones (28.7%; 99% CI, 21.1%–36.3%), nitroimidazoles (20.2%; 99% CI, 14.0%–26.4%), and penicillins (18.9%; 99% CI, 11.6%–26.2%). In NAMCS/NHAMCS, antibiotic prescribing was least frequent in emergency departments (10.8%; 99% CI, 9.5%–12.1%). Among 1,868,465 MarketScan AGE visits, antibiotics were prescribed for 13.8% (95% CI, 13.7%−13.8%), most commonly for Yersinia (46.7%; 95% CI, 21.4%–71.9%), Campylobacter (44.8%; 95% CI, 41.5%–48.1%), Shigella (39.7%; 95% CI, 35.9%–43.6%), typhoid or paratyphoid fever (32.7%; (95% CI, 27.2%–38.3%), and nontyphoidal Salmonella (31.7%; 95% CI, 29.5%–33.9%). Antibiotics were prescribed for 12.3% (95% CI, 11.7%–13.0%) of visits for viral gastroenteritis.
Conclusions:
Overall, ∼13% of AGE visits resulted in antibiotic prescriptions. Antibiotics were unnecessarily prescribed for viral gastroenteritis and some bacterial infections for which antibiotics are not recommended. Antibiotic stewardship assessments and interventions for AGE are needed in ambulatory settings.
To describe the cumulative seroprevalence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies during the coronavirus disease 2019 (COVID-19) pandemic among employees of a large pediatric healthcare system.
Design, setting, and participants:
Prospective observational cohort study open to adult employees at the Children’s Hospital of Philadelphia, conducted April 20–December 17, 2020.
Methods:
Employees were recruited starting with high-risk exposure groups, utilizing e-mails, flyers, and announcements at virtual town hall meetings. At baseline, 1 month, 2 months, and 6 months, participants reported occupational and community exposures and gave a blood sample for SARS-CoV-2 antibody measurement by enzyme-linked immunosorbent assays (ELISAs). A post hoc Cox proportional hazards regression model was performed to identify factors associated with increased risk for seropositivity.
Results:
In total, 1,740 employees were enrolled. At 6 months, the cumulative seroprevalence was 5.3%, which was below estimated community point seroprevalence. Seroprevalence was 5.8% among employees who provided direct care and was 3.4% among employees who did not perform direct patient care. Most participants who were seropositive at baseline remained positive at follow-up assessments. In a post hoc analysis, direct patient care (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.03–3.68), Black race (HR, 2.70; 95% CI, 1.24–5.87), and exposure to a confirmed case in a nonhealthcare setting (HR, 4.32; 95% CI, 2.71–6.88) were associated with statistically significant increased risk for seropositivity.
Conclusions:
Employee SARS-CoV-2 seroprevalence rates remained below the point-prevalence rates of the surrounding community. Provision of direct patient care, Black race, and exposure to a confirmed case in a nonhealthcare setting conferred increased risk. These data can inform occupational protection measures to maximize protection of employees within the workplace during future COVID-19 waves or other epidemics.
The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Externalism with respect to content is the thesis that the contents of an individual's mental states are fixed, not just by the intrinsic physical characteristics of the individual, but also in part by the external circumstances of the individual. This idea can be illustrated by means of thought experiments involving pairs of ‘twins’ who are identical with respect to their intrinsic features yet who differ mentally because of differences in their environments. The thoughts of a thirsty earthling may turn to water. Suppose that an earthling has a molecule-for-molecule twin on a very distant planet, a planet identical to Earth except that wherever Earth has H2O, Twin Earth has XYZ, which is superficially indistinguishable from water. When the twin is thirsty, her thoughts will turn instead to twater, as we may call it. Externalism about content is a metaphysical thesis, but it has epistemological implications. Many have argued that externalism is incompatible with a suitably rigorous thesis about the authoritative, introspective self-knowledge we seem to have with respect to our own thought contents.
Stephen Law developed a challenge to theism, known as the evil-god challenge (Law (2010) ). The evil-god challenge to theism is to explain why the theist's responses to the problem of evil are any better than the diabolist's – who believes in a supremely evil god – rejoinders to the problem of good, when all the theist's ploys (theodicy, sceptical theism, etc.) can be parodied by the diabolist.
In the first part of this article, I extend the evil-god challenge by showing that additional theist replies to the problem of evil (more theodicies, the privation view of evil, and others) also may be appropriated, with just as much plausibility, in support of the diabolist position. In the second part of the article, I defend the evil-god challenge against several objections.
The anticipated release of EnlistTM cotton, corn, and soybean cultivars likely will increase the use of 2,4-D, raising concerns over potential injury to susceptible cotton. An experiment was conducted at 12 locations over 2013 and 2014 to determine the impact of 2,4-D at rates simulating drift (2 g ae ha−1) and tank contamination (40 g ae ha−1) on cotton during six different growth stages. Growth stages at application included four leaf (4-lf), nine leaf (9-lf), first bloom (FB), FB + 2 wk, FB + 4 wk, and FB + 6 wk. Locations were grouped according to percent yield loss compared to the nontreated check (NTC), with group I having the least yield loss and group III having the most. Epinasty from 2,4-D was more pronounced with applications during vegetative growth stages. Importantly, yield loss did not correlate with visual symptomology, but more closely followed effects on boll number. The contamination rate at 9-lf, FB, or FB + 2 wk had the greatest effect across locations, reducing the number of bolls per plant when compared to the NTC, with no effect when applied at FB + 4 wk or later. A reduction of boll number was not detectable with the drift rate except in group III when applied at the FB stage. Yield was influenced by 2,4-D rate and stage of cotton growth. Over all locations, loss in yield of greater than 20% occurred at 5 of 12 locations when the drift rate was applied between 4-lf and FB + 2 wk (highest impact at FB). For the contamination rate, yield loss was observed at all 12 locations; averaged over these locations yield loss ranged from 7 to 66% across all growth stages. Results suggest the greatest yield impact from 2,4-D occurs between 9-lf and FB + 2 wk, and the level of impact is influenced by 2,4-D rate, crop growth stage, and environmental conditions.
John M. Collins presents the first comprehensive history of martial law in the early modern period. He argues that rather than being a state of exception from law, martial law was understood and practiced as one of the King's laws. Further, it was a vital component of both England's domestic and imperial legal order. It was used to quell rebellions during the Reformation, to subdue Ireland, to regulate English plantations like Jamestown, to punish spies and traitors in the English Civil War, and to build forts on Jamaica. Through outlining the history of martial law, Collins reinterprets English legal culture as dynamic, politicized, and creative, where jurists were inspired by past practices to generate new law rather than being restrained by it. This work asks that legal history once again be re-integrated into the cultural and political histories of early modern England and its empire.
Cores dating back to deglaciation were taken from three lakes in Atlantic Canada and analyzed for arcellaceans and pollen. Paleotemperatures and paleo-precipitation were calculated from the pollen data using transfer functions. A sudden warming is recorded by the pollen around 10,000 years B.P., followed by a general warming to the mid Holocene Hypsithermal, then by a decrease in temperature and increase in effective precipitation to the present. The three lakes, two in western Newfoundland and one in eastern Nova Scotia, contain similar late glacial (13-10 ka), early Holocene (10-8 ka), mid Holocene (8-4 ka), and late Holocene (4-0 ka) arcellacean assemblages. Immediately following retreat of the ice sheets, Centropyxis aculeata, Centropyxis constricta, Difflugia oblonga, Difflugia urceolata, and Difflugia corona were common. The latter part of the late glacial is characterized by sparse assemblages dominated by C. aculeata. The arcellacean record thus suggests a climatic reversal in Atlantic Canada between 11,500 and 10,000 years B.P., analogous to the Younger Dryas, although this is not recorded by the pollen. Species diversity increased sharply at the beginning of the Holocene, and D. oblonga is the dominant taxon in early Holocene sediments. Difflugia oblonga remained common through the mid Holocene, but percentages of C. aculeata were very low, and Pontigulasia compressa and Difflugia bacillifera peaked in abundance during the Hypsithermal. The late Holocene is characterized by a resurgence in C. aculeata at the expense of other taxa. The increase in Heleopera sphagni and Nebella collaris since 5,000 years B.P. at the two sites in southwestern Newfoundland reflects paludification in response to increased precipitation since the Hypsithermal. Because the changes in arcellacean assemblages are regionally synchronous in all three lakes and coincide with climatically driven vegetational successions indicated by the pollen record, arcellaceans appear to respond to climatic change, and thus may be useful paleoecological and paleolimnological indicators. With their quicker generation time, these protists may be better suited than pollen to recording short-lived phenomena, like the mid-Holocene Hypsithermal and the Younger Dryas reversal.