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To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Design:
Prospective observational study.
Setting:
Neonatal intensive care unit (NICU).
Methods:
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
Results:
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
Conclusions:
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
Whole-genome sequencing (WGS) has traditionally been used in infection prevention to confirm or refute the presence of an outbreak after it has occurred. Due to decreasing costs of WGS, an increasing number of institutions have been utilizing WGS-based surveillance. Additionally, machine learning or statistical modeling to supplement infection prevention practice have also been used. We systematically reviewed the use of WGS surveillance and machine learning to detect and investigate outbreaks in healthcare settings.
Methods:
We performed a PubMed search using separate terms for WGS surveillance and/or machine-learning technologies for infection prevention through March 15, 2021.
Results:
Of 767 studies returned using the WGS search terms, 42 articles were included for review. Only 2 studies (4.8%) were performed in real time, and 39 (92.9%) studied only 1 pathogen. Nearly all studies (n = 41, 97.6%) found genetic relatedness between some isolates collected. Across all studies, 525 outbreaks were detected among 2,837 related isolates (average, 5.4 isolates per outbreak). Also, 35 studies (83.3%) only utilized geotemporal clustering to identify outbreak transmission routes. Of 21 studies identified using the machine-learning search terms, 4 were included for review. In each study, machine learning aided outbreak investigations by complementing methods to gather epidemiologic data and automating identification of transmission pathways.
Conclusions:
WGS surveillance is an emerging method that can enhance outbreak detection. Machine learning has the potential to identify novel routes of pathogen transmission. Broader incorporation of WGS surveillance into infection prevention practice has the potential to transform the detection and control of healthcare outbreaks.
Merton envisioned his norms of science at a time when peer-reviewed journals controlled scientific communication. Technologies for sharing and finding content have since divorced the certification and amplification of science, generating systemic vulnerabilities. Certified amplification – a new Mertonian-styled norm – enjoins their recoupling and introduces a taxonomy of strategies adopted by institutions to close the certification-amplification gap, including the proportioning of the one to the other. Examples illustrating each taxonomic type collectively paint a picture of an ethos employing a rich range of certification and amplification techniques and emerging in a decentralized fashion across heterogeneous objects, communication modalities, and institutions.
The dispersion relation of a surface wave generated by a drifting plasma in an infinite duct surrounded by vacuum is derived non-relativistically by means of the Vlasov equation. The kinematic boundary condition imposed on the distribution function, the specular reflection conditions on the four sides of duct, can be satisfied by placing an infinite number of fictitious surface charge sheets spaced by the duct widths. The surface wave mode is specifically the transverse magnetic mode, often called the surface polariton, which propagates with phasor $\exp ({{\rm i}k_zz-{\rm i}\omega t})$. The method of placing appropriate fictitious surface charge sheets enables one to treat the surface waves in semi-infinite, slab and duct plasmas simultaneously on an equal footing, kinetically. The streaming effect manifests itself through the Doppler-shifted frequency and a correction-like term ${u^2}/{c^2}$, where u is the streaming velocity and c is the speed of light.
Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler’s Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59], p = 0.006), verbal composite (−1.93 [−3.33, −0.53], p = 0.007), and information scale (−0.41 [−0.70, −0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children’s cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.
In real gas turbines, multiple nozzles are used instead of a single-nozzle; therefore, interactions between flames are inevitable. In this study, the effects of flame-flame interaction on the emission characteristics and lean blowout limit were analysed in a CH4-fueled single- and dual-nozzle combustor. OH* chemiluminescence imaging showed that a flame-interacting region, where the two flames from the nozzles were merged, was present in the dual-nozzle combustor, unlike the single-nozzle combustor. Flow-field measurements using particle image velocimetry confirmed that a faster velocity region was formed at the flame merging region, thereby hindering flame stabilisation. In addition, we compared the emission indices of NOx and CO between the two combustors. The emission indices of CO were not significantly different; however, a distinct effect of flame-flame interaction was indicated in NOx. To understand the effect of flame-flame interaction on NOx emissions, we measured temperature distribution using a multi-point thermocouple. Results showed that a wider high-temperature region was formed in the dual-nozzle combustor compared to the single-nozzle combustor; this was attributable to the high OH* chemiluminescence intensity in the flame-interacting region. Furthermore, it was confirmed that the size of this interacting region caused the deformation of the temperature distribution in the combustor, which can induce a difference in the increase ratio of NOx emission between high and low equivalence ratio ranges. In conclusion, we confirmed that flame-flame interaction significantly affected temperature distribution in the downstream of the flame, and the change in temperature distribution contributed primarily to the varying concentration of the emission gas.
We define positively expansive semigroups of linear operators on Banach spaces. We characterize these semigroups in terms of the point spectrum of the infinitesimal generator. In particular, we prove that a positively expansive semigroup is neither uniformly bounded nor equicontinuous. We apply our results to the Lasota equation.
OBJECTIVES/GOALS: To evaluate whether a low cost, functional dynamic 3-D printed upper extremity (UE) orthosis could be designed, fabricated and used by children with cerebral palsy (CP) with severe unilateral UE involvement and the ability of common standardized instruments to assess its effectiveness. METHODS/STUDY POPULATION: Five patients, ages 13-17 years, with CP and unilateral UE involvement, MACS levels III-IV, were enrolled. Custom forearm thumb opponens orthosis and dynamic upper extremity orthosis (DUEO) were designed and fabricated by a multidisciplinary team for use during 8 one-hour occupational therapy sessions targeting bimanual UE training. Pre- and post-assessments included Assisting Hand Assessment(AHA), Melbourne-2(MA-2), Pediatric Motor Activity Log-Revised(PMAL-R), and PedsQL Measurement Model for the Pediatric Quality of Life Inventory: CP Module(Peds-QL). RESULTS/ANTICIPATED RESULTS: The 3D printed orthotic device is custom fit to the patient based on scans of their arm and is designed with a tensioning system that allows for functional usage of the arm. It incorporates a rigid polymer to provide support and flexible material for comfort where appropriate. Overall, higher post-treatment scores were found for the majority of participants using the custom orthotic. Four made minimal clinically important differences (MCID) in the AHA. Three met MCID scores in subtests of MA-2 (two positive and one negative). Patient-reported outcome improvements were found for PMAL-R for four, but only one met MCID and at least three reported improvements in more than one domain of PedsQL. DISCUSSION/SIGNIFICANCE: Children with CP may often present with UE impairment, yet current therapeutic orthoses only target the progression of contractures and are still limited by cost and discomfort. Our team designed and fabricated a functional, low cost, 3D printed orthosis that showed significant gains in UE function.
OBJECTIVES/GOALS: Fertility preservation (FP) allows transgender and gender diverse (TGD) patients undergoing gender-affirming therapy to pursue genetic parenthood. Barriers to care exist leading to its underutilization; while these barriers to care have been investigated, the true utilization rates of FP services by TGD patients are unknown. METHODS/STUDY POPULATION: This study includes a retrospective chart review of adult and pediatric patients from Mayo Clinics Transgender and Intersex Specialty Care Clinic who have provided research authorization. We will assess if FP was discussed and review if the patients proceeded to make appointments with either the Department of Reproductive Endocrinology & Infertility or the Department of Urology. FP terms include semen cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation. Patient demographic data will be collected to determine associations between utilization rate and age, sex recorded at birth, gender identity, race, ethnicity, and variables related to socioeconomic determinants of health. RESULTS/ANTICIPATED RESULTS: We hypothesize that the rate of FP utilization will be higher for patients who begin to affirm their gender at the age of 25 or older, and for those seeking feminization treatment in comparison to pre-pubescent adolescents, young adults, and transgender men. Of FP options, semen cryopreservation will be most utilized, followed by oocyte cryopreservation; both will be more utilized than embryo cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, and ovarian tissue cryopreservation. Employment, and insurance status and coverage, will play a role in FP service utilization after initial consult. This study was approved by Mayo Clinics Institutional Review Board. Data on N=611 patients is expected to be abstracted and analyzed prior to Translation 2022. DISCUSSION/SIGNIFICANCE: This study will be one of the first to examine the rate of FP utilization by TGD patients with respect to the age and timing of gender-affirming therapy initiation. Understanding the rate of utilization of FP services will allow for the creation of age-appropriate education materials for TGD patients pursuing gender affirmation and FP at Mayo Clinic.
Wetland sediments are valuable archives of environmental change but can be challenging to date. Terrestrial macrofossils are often sparse, resulting in radiocarbon (14C) dating of less desirable organic fractions. An alternative approach for capturing changes in atmospheric 14C is the use of terrestrial microfossils. We 14C date pollen microfossils from two Australian wetland sediment sequences and compare these to ages from other sediment fractions (n = 56). For the Holocene Lake Werri Berri record, pollen 14C ages are consistent with 14C ages on bulk sediment and humic acids (n = 14), whilst Stable Polycyclic Aromatic Carbon (SPAC) 14C ages (n = 4) are significantly younger. For Welsby Lagoon, pollen concentrate 14C ages (n = 21) provide a stratigraphically coherent sequence back to 50 ka BP. 14C ages from humic acid and >100 µm fractions (n = 13) are inconsistent, and often substantially younger than pollen ages. Our comparison of Bayesian age-depth models, developed in Oxcal, Bacon and Undatable, highlight the strengths and weaknesses of the different programs for straightforward and more complex chrono-stratigraphic records. All models display broad similarities but differences in modeled age-uncertainty, particularly when age constraints are sparse. Intensive dating of wetland sequences improves the identification of outliers and generation of robust age models, regardless of program used.
OBJECTIVES/GOALS: Over 30% of patients with rheumatoid arthritis (RA) exhibit fibromyalgianess, a symptom cluster associated with increased pain sensitivity. Up to half of RA patients use oral glucocorticoids (GCs) long-term despite their known, dose-dependent toxicity. We examined the association between fibromyalgianess and oral GC persistence in RA patients. METHODS/STUDY POPULATION: We used data from the Central Pain in Rheumatoid Arthritis (CPIRA) cohort to follow participants with active RA on oral prednisone who initiated a new disease-modifying anti-rheumatic drug. We measured fibromyalgianess using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key fibromyalgia features often superimposed upon RA. We stratified fibromyalgianess severity as follows: FSQ<8 low, 8-10 moderate, >10 high/very high. We defined GC persistence as GC use at 3 month followup visit. We assessed the association between baseline fibromyalgianess (exposure) and GC persistence at followup (outcome) using multiple logistic regression, adjusted for demographics, RA duration, serostatus, and inflammatory activity measured by swollen joint count and C reactive protein. RESULTS/ANTICIPATED RESULTS: Of 97 participants on prednisone at baseline, 65% were taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent GC use, compared to 84% with high or very high fibromyalgianess. After adjustment as outlined above, participants with high/very high baseline fibromyalgianess remained more likely to be on prednisone at follow-up, relative to those with low fibromyalgianess (OR 4.99 [95% CI 1.20 – 20.73]). DISCUSSION/SIGNIFICANCE: In this cohort of patients with active RA, high fibromyalgianess is associated with persistent GC use, independent of inflammatory activity. This finding suggests non-inflammatory pain related to fibromyalgianess may be misclassified as inflammatory pain related to RA disease activity.
Multifetal pregnancies are at risk of adverse maternal, neonatal and long-term health outcomes, and gestational weight gain (GWG) is a potentially modifiable risk factor for several of these. However, studies assessing the associations of GWG with long-term health in twins are rare, and studies which do assess these associations in twins often do not account for gestational age. Since longer gestations are likely to lead to larger GWG and lower risk of adverse outcomes, adjusting for gestational age is necessary to better understand the association of GWG with twin health outcomes. We aimed to explore long-term associations of GWG-for-gestational-age with twin anthropometric measures. The Peri/Postnatal Epigenetic Twins Study (PETS) is a prospective cohort study, which recruited women pregnant with twins from 2007 to 2009. Twins were followed-up at 18 months and 6 years of age. GWG-for-gestational-age z-scores were calculated from pre-pregnancy weight and weight at delivery. We fitted regression models to assess associations of GWG with twin weight, height and BMI at birth, 18 months, and 6 years. Of the 250 women in the PETS, 172 had GWG measured throughout pregnancy. Overall, higher GWG-for-gestational-age z-scores were associated with higher birthweight (β: 0.32 z-scores, 95% Confidence Interval (95% CI): 0.19, 0.45), BMI (β: 0.29 z-scores, 95% CI: 0.14, 0.43) and length (β: 0.27 z-scores, 95% CI: 0.09, 0.45). However, these associations were not observed at 18 months or 6 years of age. GWG was associated with twin length, weight and BMI at birth but not during childhood. Further research is needed to determine the long-term effects of GWG on twin health outcomes.
Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied.
Methods
58 pre-adolescent children (aged 9–10-years) with BED (mBMI = 25.05; s.d. = 5.40) and 66 age, BMI and developmentally matched control children (mBMI = 25.78; s.d. = 0.33) were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward [orbitofrontal cortex (OFC), nucleus accumbens, amygdala] and inhibitory control [dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)] networks via hypothesis-driven seed-to-seed analyses, and secondary seed-to-voxel analyses.
Results
Findings revealed reduced FC between the dlPFC and amygdala, and between the ACC and OFC in pre-adolescent children with BED, relative to controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses.
Conclusions
Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.
Unresolved states of mind regarding experiences of loss/abuse (U/d) are identified through lapses in the monitoring of reasoning, discourse, and behavior surrounding loss/abuse in response to the Adult Attachment Interview. Although the coding system for U/d has been widely used for decades, the individual indicators of unresolved loss/abuse have not been validated independently of the development sample. This study examined the psychometric validity of U/d, using individual participant data from 1,009 parent–child dyads across 13 studies. A latent class analysis showed that subsets of commonly occurring U/d indicators could differentiate interviewees with or without unresolved loss/abuse. Predictive models suggested a psychometric model of U/d consisting of a combination of these common indicators, with disbelief and psychologically confused statements regarding loss being especially important indicators of U/d. This model weakly predicted infant disorganized attachment. Multilevel regression analysis showed no significant association between ratings of unresolved other trauma and infant disorganized attachment, over and above ratings of unresolved loss/abuse. Altogether, these findings suggest that the coding system of U/d may have been overfitted to the initial development sample. Directions for further articulation and optimization of U/d are provided.
In-person religious service attendance has been linked to favorable health and well-being outcomes. However, little research has examined whether online religious participation improves these outcomes, especially when in-person attendance is suspended.
Methods
Using longitudinal data of 8951 UK adults, this study prospectively examined the association between frequency of online religious participation during the stringent lockdown in the UK (23 March –13 May 2020) and 21 indicators of psychological well-being, social well-being, pro-social/altruistic behaviors, psychological distress, and health behaviors. All analyses adjusted for baseline socio-demographic characteristics, pre-pandemic in-person religious service attendance, and prior values of the outcome variables whenever data were available. Bonferroni correction was used to correct for multiple testing.
Results
Individuals with online religious participation of ≥1/week (v. those with no participation at all) during the lockdown had a lower prevalence of thoughts of self-harm in week 20 (odds ratio 0.24; 95% CI 0.09–0.62). Online religious participation of <1/week (v. no participation) was associated with higher life satisfaction (standardized β = 0.25; 0.11–0.39) and happiness (standardized β = 0.25; 0.08–0.42). However, there was little evidence for the associations between online religious participation and all other outcomes (e.g. depressive symptoms and anxiety).
Conclusions
There was evidence that online religious participation during the lockdown was associated with some subsequent health and well-being outcomes. Future studies should examine mechanisms underlying the inconsistent results for online v. in-person religious service attendance and also use data from non-pandemic situations.
We present a new and straightforward algorithm that simulates exact sample paths for a generalized stress-release process. The computation of the exact law of the joint inter-arrival times is detailed and used to derive this algorithm. Furthermore, the martingale generator of the process is derived, and induces theoretical moments which generalize some results of [3] and are used to demonstrate the validity of our simulation algorithm.
We present the most sensitive and detailed view of the neutral hydrogen (
${\rm H\small I}$
) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal
${\rm H\small I}$
in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K (
$1.6\,\mathrm{mJy\ beam}^{-1}$
)
$\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$
spectral channel with an angular resolution of
$30^{\prime\prime}$
(
${\sim}10\,\mathrm{pc}$
). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire
${\sim}25\,\mathrm{deg}^2$
field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes
${\rm H\small I}$
test observations.
Ascribing autonomous status to agents is a valuable practice. As such, we ought to care about how we engage in practices of autonomy ascription. However, disagreement between first-personal experiences of an agent's autonomy and third-personal determinations of their autonomy presents challenges of ethical and epistemic concern. My view is that insights from a dialogical rather than nondialogical account of autonomy give us the resources to combat the challenges associated with autonomy ascription. I draw on Andrea Westlund's account of dialogical autonomy—on which autonomy requires a dialogical disposition to hold oneself answerable to external critical perspectives—to make my case.
Modular coral-like fossils occur in thrombolitic reefal beds at two stratigraphic levels within the Lower Ordovician (Floian) Barbace Cove Member of the Boat Harbour Formation, in the St. George Group of western Newfoundland. They are here assigned to Reptamsassia n. gen.; R. divergens n. gen. n. sp. is present at both levels, whereas a comparatively small-module species, R. minuta n. gen. n. sp., is confined to the upper level. Reptamsassia n. gen. resembles the Ordovician genus Amsassia in its phacelocerioid structure, back-to-back walls of adjoining modules, module increase by longitudinal fission involving infoldings of the wall, tabula-like structures that are continuous with the vertical module wall, and calices with concave-up bottoms. The new genus is differentiated by its encrusting habit, modules with highly variable growth directions and shapes throughout skeletal growth, and modules that may separate slightly or diverge from one another following fission. Together, Amsassia and Reptamsassia n. gen. are considered to represent a distinct group of calcareous algae, the Amsassiaceae n. fam., which possibly belongs to the green algae. The Early Ordovician origination of Amsassia followed by Reptamsassia n. gen. contributed to the beginning of the rise in diversity on a global scale and in reefal settings during the Great Ordovician Biodiversification Event. Reptamsassia minuta n. gen. n. sp. was an obligate symbiont that colonized living areas on its host, R. divergens n. gen. n. sp., with isolated modules of R. divergens n. gen. n. sp. able to persist in the resulting intergrowth with R. minuta n. gen. n. sp. This is the earliest known symbiotic intergrowth of macroscopic modular species, exemplifying the development of ecologic specialization and ecosystem complexity in Early Ordovician reefs.