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Mr. C, a 75-year-old man, noticed difficulty remembering names and adding numbers after wakening while on vacation. Although these problems were quite subtle, his wife was puzzled because he seemed to have no difficulty the day before. One week later, he noted that “something was wrong” but could not describe the changes in detail. He felt that his balance was “not right” and experienced difficulty keeping track of his golf scores. Over the next few months, he developed word-finding problems and had difficulty expressing himself. He was very forgetful, had trouble problem solving, was distractible, and was unable to do simple calculations. Whereas he had previously been very reserved, he started talking with others in a more open way than he would normally have done. He continued to complain of balance problems and started to notice changes in his handwriting.
Disadvantages of intravenous therapeutic unfractionated heparin, the first-line anti-coagulant agent in children with complex congenital heart disease, include unpredictable pharmacokinetics requiring frequent phlebotomies and the need for continuous intravenous access.
To compare efficacy and safety of low-molecular-weight heparin administered by a subcutaneous indwelling catheter with intravenous unfractionated heparin.
Materials and methods:
Clinical data from 31 inpatients prospectively enrolled to receive subcutaneous low-molecular-weight heparin were compared with those from a historical group of 44 inpatients receiving intravenous unfractionated heparin. Investigation of parents’ satisfaction by telephone survey.
The percentage of anti-factor Xa levels outside therapeutic range was lower in the subcutaneous low-molecular-weight heparin group compared with the percentage of activated partial thromboplastin times outside therapeutic range in the intravenous unfractionated heparin group (40% versus 90%, p < 0.001). Neither group had a major complication. Transient local reactions occurred in 19% of patients of the subcutaneous low-molecular-weight heparin group. The number of needle punctures and that of placement of indwelling catheters were significantly lower in the subcutaneous low-molecular-weight heparin compared with the intravenous unfractionated heparin group (p < 0.001). In total, 84.2% of parents in the subcutaneous low-molecular-weight heparin group reported a positive experience when asked about comparison with prior intravenous unfractionated heparin treatment.
Subcutaneous low-molecular-weight heparin offers a safe anti-coagulation regimen for children with complex congenital heart disease providing more efficient therapeutic anti-coagulation and a reduction in needle punctures, thus causing less pain and anxiety in this children.
During glacial times, the North Atlantic region was affected by serious climate changes corresponding to Dansgaard-Oeschger cycles that were linked to dramatic shifts in sea temperature and moisture transfer to the continents. However, considerable efforts are still needed to understand the effects of these shifts on terrestrial environments. In this context, the Iberian Peninsula is particularly interesting because of its close proximity to the North Atlantic, although the Iberian interior lacks paleoenvironmental information so far because suitable archives are rare. Here we provide an accurate impression of the last glacial environmental developments in central Iberia based on comprehensive investigations using the upper Tagus loess record. A multi-proxy approach revealed that phases of loess formation during Marine Isotope Stage (MIS) 2 (and upper MIS 3) were linked to utmost aridity, coldness, and highest wind strengths in line with the most intense Greenland stadials also including Heinrich Events 3–1. Lack of loess deposition during the global last glacial maximum (LGM) suggests milder conditions, which agrees with less-cold sea surface temperatures (SST) off the Iberian margin. Our results demonstrate that geomorphological system behavior in central Iberia is highly sensitive to North Atlantic SST fluctuations, thus enabling us to reconstruct a detailed hydrological model in relation to marine–atmospheric circulation patterns.
Despite broad evidence suggesting that adversity-exposed youth experience an impaired ability to recognize emotion in others, the underlying biological mechanisms remains elusive. This study uses a multimethod approach to target the neurological substrates of this phenomenon in a well-phenotyped sample of youth meeting diagnostic criteria for posttraumatic stress disorder (PTSD). Twenty-one PTSD-afflicted youth and 23 typically developing (TD) controls completed clinical interview schedules, an emotion recognition task with eye-tracking, and an implicit emotion processing task during functional magnetic resonance imaging )fMRI). PTSD was associated with decreased accuracy in identification of angry, disgust, and neutral faces as compared to TD youth. Of note, these impairments occurred despite the normal deployment of visual attention in youth with PTSD relative to TD youth. Correlation with a related fMRI task revealed a group by accuracy interaction for amygdala–hippocampus functional connectivity (FC) for angry expressions, where TD youth showed a positive relationship between anger accuracy and amygdala–hippocampus FC; this relationship was reversed in youth with PTSD. These findings are a novel characterization of impaired threat recognition within a well-phenotyped population of severe pediatric PTSD. Further, the differential amygdala–hippocampus FC identified in youth with PTSD may imply aberrant efficiency of emotional contextualization circuits.
A major challenge of airway management is safe care of the patient with a narrowed airway. Small tracheal tubes offer one solution but pose a problem with ventilation. While inspiration may be achieved by use of a high-pressure source to overcome airway resistance, two problems exist: first, the high-pressure source demands technical excellence and exposes the patient to a high risk of barotrauma; second, conventional (passive) exhalation through a narrow tube is slow and cannot achieve a normal minute ventilation with a tracheal tube of less than 4.5 mm diameter. Recently technical developments have led to the ability to assist expiration and make it, like inspiration, an active process. This technology is used in the Ventrain manual ventilator, the 2.4 mm wide Tritube tracheal tube and the Evone automatic ventilator. These new devices and the applied technology enable solutions for safe management of the narrowed upper airway.
Nearly 1 in 5 children in the United States lives in a household whose income is below the official federal poverty line, and more than 40% of children live in poor or near-poor households. Research on the effects of poverty on children's development has been a focus of study for many decades and is now increasing as we accumulate more evidence about the implications of poverty. The American Academy of Pediatrics recently added “Poverty and Child Health” to its Agenda for Children to recognize what has now been established as broad and enduring effects of poverty on child development. A recent addition to the field has been the application of neuroscience-based methods. Various techniques including neuroimaging, neuroendocrinology, cognitive psychophysiology, and epigenetics are beginning to document ways in which early experiences of living in poverty affect infant brain development. We discuss whether there are truly worthwhile reasons for adding neuroscience and related biological methods to study child poverty, and how might these perspectives help guide developmentally based and targeted interventions and policies for these children and their families.
Up until now, there is much debate about the role of asymptomatic patients and pauci-symptomatic patients in severe acute respiratory syndrome novel coronavirus 2 (SARS-CoV-2) transmission, and little is known about the kinetics of viral ribonucleic acid (RNA) shedding in these populations. This article aims to describe key features and the nature of asymptomatic and pauci-symptomatic SARS-CoV-2 infected patients. The cohort consisted of six participants, three pairs, which were infected with SARS-CoV-2 during February 2020 on board the Diamond Princess. Of the six confirmed (reverse transcription polymerase chain reaction [RT-PCR]) cases, four were initially diagnosed in Japan and two upon their arrival to Israel. Duration of infection was between four days and up to 26 days. Of the six patients, three were completely asymptomatic and the others were pauci-symptomatic. All five patients in whom a computerized tomography (CT) scan was performed had lung pathology. In one patient, infectivity was tested using cell culture and a cytopathic effect was demonstrated. A serology test was performed in three of the patients and all three had a positive immunoglobulin G (IgG) four to eight weeks after disease onset. This case series demonstrates that asymptomatic and pauci-symptomatic patients may play a role in infection transmission by demonstrating probable transmission among asymptomatic spouses and by demonstrating a viable virus via a cell culture. Additionally, asymptomatic and pauci-symptomatic patients can have lung pathology and developing IgG antibodies.
Identifying predictors of patient outcomes evaluated over time may require modeling interactions among variables while addressing within-subject correlation. Generalized linear mixed models (GLMMs) and generalized estimating equations (GEEs) address within-subject correlation, but identifying interactions can be difficult if not hypothesized a priori. We evaluate the performance of several variable selection approaches for clustered binary outcomes to provide guidance for choosing between the methods.
We conducted simulations comparing stepwise selection, penalized GLMM, boosted GLMM, and boosted GEE for variable selection considering main effects and two-way interactions in data with repeatedly measured binary outcomes and evaluate a two-stage approach to reduce bias and error in parameter estimates. We compared these approaches in real data applications: hypothermia during surgery and treatment response in lupus nephritis.
Penalized and boosted approaches recovered correct predictors and interactions more frequently than stepwise selection. Penalized GLMM recovered correct predictors more often than boosting, but included many spurious predictors. Boosted GLMM yielded parsimonious models and identified correct predictors well at large sample and effect sizes, but required excessive computation time. Boosted GEE was computationally efficient and selected relatively parsimonious models, offering a compromise between computation and parsimony. The two-stage approach reduced the bias and error in regression parameters in all approaches.
Penalized and boosted approaches are effective for variable selection in data with clustered binary outcomes. The two-stage approach reduces bias and error and should be applied regardless of method. We provide guidance for choosing the most appropriate method in real applications.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Quasicrystalline alloys and their composites have been extensively studied due to their complex atomic structures, mechanical properties, and their unique tribological and thermal behaviors. However, technological applications of these materials have not yet come of age and still require additional developments. In this review, we discuss the recent advances that have been made in the last years toward optimizing fabrication processes and properties of Al-matrix composites reinforced with quasicrystals. We discuss in detail the high-strength rapid-solidified nanoquasicrystalline composites, the challenges involved in their manufacturing processes and their properties. We also bring the latest findings on the fabrication of Al-matrix composites reinforced with quasicrystals by powder metallurgy and by conventional metallurgical processes. We show that substantial developments were made over the last decade and discuss possible future studies that may result from these recent findings.
The paper looks at several episodes in which R. Yirmiyah is rebuked for questions that are portrayed as epistemologically destabilizing to the rabbinic legal project. I argue that R. Yirmiyah is portrayed as a caricature of late rabbinic scholastic thought, and that his characterization enables the writers of the Bavli to hold their own scholastic tendencies up to critique while also drawing protective boundaries around the analytical direction their legal culture has taken. I also read the passages together to demonstrate that the Bavli functions as a unified literary work in previously unacknowledged ways. These episodes form a sort of nonlinear plot, a web of stories that produce a character with his own “history.” There may be no historical rabbinic nuisance named R. Yirmiyah, but there is certainly a constructed literary one, whose reappearance throughout the Talmud plays an important role in working out tensions within the rabbinic legal project.
We evaluated whether memory recall following an extended (1 week) delay predicts cognitive and brain structural trajectories in older adults.
Clinically normal older adults (52–92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178–207, mean ages = 74–76) at annual study visits occurring approximately 15–18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.
Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044).
Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories.
In Germany, sheep are the main source of human Q fever epidemics, but data on Coxiella burnetii (C. burnetii) infections and related risk factors in the German sheep population remain scarce. In this cross-sectional study, a standardised interview was conducted across 71 exclusively sheep as well as mixed (sheep and goat) farms to identify animal and herd level risk factors associated with the detection of C. burnetii antibodies or pathogen-specific gene fragments via univariable and multivariable logistic regression analysis. Serum samples and genital swabs from adult males and females of 3367 small ruminants from 71 farms were collected and analysed using ELISA and qPCR, respectively. On animal level, univariable analysis identified young animals (<2 years of age; odds ratio (OR) 0.33; 95% confidence interval (CI) 0.13–0.83) to reduce the risk for seropositivity significantly (p < 0.05). The final multivariable logistic models identified lambing all year-round (OR 3.46/3.65; 95% CI 0.80–15.06/0.41–32.06) and purchases of sheep and goats (OR 13.61/22.99; 95% CI 2.86–64.64/2.21–239.42) as risk factors on herd level for C. burnetii infection detected via ELISA and qPCR, respectively.
Background: Pasco County Fire Rescue (PCFR) is a rapidly growing suburban fire department located in Florida. PCFR employs >500 firefighters (all cross-trained as either emergency medical technicians or paramedics) in 27 stations to provide both emergency medical services (EMS) and fire suppression response. Although multiple studies have established that pathogens are present in both apparatus and stations within the fire service, there is a knowledge gap regarding the effectiveness of cleaning and disinfecting protocols in this specific setting. Methods: In total, 65 high-touch surfaces in 11 vehicles (ambulances and engines) and common areas of 2 fire stations were swabbed before and after disinfection. Vehicle surfaces swabbed included seats, cabinet doors, door handles, stretchers, medical equipment, keyboard, steering wheels, shared headsets and hand rails. Inside the stations, the refrigerator handle, television remote, radio and alarm buttons, door handles, and locker handles were swabbed. Immediately following the initial swab collection, the surfaces were disinfected with hydrogen peroxide wipes and disinfectant cleaner sprayed through an electrostatic system. The same surfaces were then swabbed after disinfection. Colony-forming units (CFUs) were quantified using standard microbiological techniques by a third-party laboratory. Statistical analysis was performed on the resulting bacterial counts using Minitab version 18.1 software. Results: We detected statistically significant decreases in total bacteria, yeast, and mold counts following implementation of this disinfection protocol. The predisinfection mean of bacteria, yeast, and mold counts for all surfaces combined was reduced 96% after disinfection (from 254,637 CFU to 9,392 CFU). Conclusions: Cleaning and disinfection of surfaces in PCFR emergency vehicles and fire station common areas with the agents described above effectively reduced contamination with bacteria, yeast, and mold spores. The PCFR has implemented this disinfection protocol as a tool in eliminating EMS vehicles and the station environment as reservoirs of infection for patients, visitors, and firefighters. Future efforts will include assessing the impact of regular cleaning and disinfection on baseline levels of bacteria, yeast, and mold spores.
Background: Hepatitis A cases have been regularly increasing in Florida since 2016, after remaining relatively stable for several years. Between January 1, 2019, and October 19, 2019, 2,847 cases of hepatitis were reported to the Florida Department of Health, including 2,209 hospitalizations and 41 deaths due to infection with hepatitis A1. At least 93% of these cases was acquired within the state of Florida.1 During this outbreak, Pasco County clearly emerged as a focal point for new cases. As of week 42 of 2019, Pasco County was the second-highest county for new cases (n = 484) and the leading county for deaths due to hepatitis A infection (n = 8). Risk factors identified from hepatitis A cases reported between January 1, 2019, and October 19, 2019, included any drug use (57%), injection drug use (37%), noninjection drug use (35%), homelessness (22%), and being a man who had sexual intercourse with other men (MSM, 4%).1 Moreover, 33% of newly reported cases were interviewed and denied risk factors; 1 (20%) had recently been incarcerated or was currently incarcerated.1 Individuals with these risk factors are often individuals who also require emergency medical services (EMS). On August 1, 2019, a public health emergency (PHE) was issued for the entire state of Florida. The existence of a PHE allows for paramedics to administer vaccine (with the approval of the fire rescue medical director). Pasco County Fire Rescue routinely operates 28 advanced life support (ALS) ambulances with either a crew of 2 paramedics or a paramedic/EMT pair. On October 7, 2019, the Pasco County Board of County Commissioners (BCC) approved a Memorandum of Understanding between the Florida Department of Health in Pasco County, the Pasco County Fire Rescue Medical Director, and the BCC for ALS crews to provide hepatitis A vaccination to noncritical (ie, basic life support) patients during routine contact. This effort appears to be the first within the of Florida. Pasco County Fire Rescue (PCFR) began stocking hepatitis A vaccine on January 1, 2020 and ceased participation in the program on March 1, 2020. During the window of participation, PCFR responded to approximately 6,570 calls in which the patient would have been non-critical and eligible for hepatitis A vaccination. Twelve hepatitis A vaccinations (0.18%) were administered. Crews verbalized concerns about adding vaccination to their job description, feelings of being overwhelmed with existing emergency medical services (EMS) responsibilities, apathy regarding the potential benefit of provision of vaccine, and perception that successful participation in a vaccine campaign would lead to additional community paramedicine responsibilities. The vaccine program was terminated early due to the significant demands on EMS as SARS-CoV2 impacted Pasco County. This trial highlights the need for crew investments and buy-in for future partial or full community paramedicine initiatives.
1. Florida Department of Health, Hepatitis A Surveillance State Report, Week 42.
Background: Multiple studies have demonstrated that pathogens are present in both apparatus and stations within the fire service. Pasco County Fire Rescue’s (PCFR’s) 500+ firefighters routinely wear boots to trauma scenes and into patient’s residences and then into the dormitory and living areas of the fire stations. Pasco County Fire Rescue (PCFR) recently participated in a larger effort to identify the bacteria, yeast, and mold that firefighters, emergency medical technicians, and paramedics are exposed to on apparatuses and the station living environment during a typical shift. During these efforts to swab multiple touch points within apparatus (ambulances and engines) and common areas of the stations, firefighters’ boots were identified as a significant source of bacterial contamination. Methods: Swabs of 191 surfaces in 23 vehicles and 5 fire stations were collected, including 3 swabs from the bottom of firefighter boots. Results: Firefighter boots had the highest bacterial CFUs of all locations swabbed, with >900,000 and 378,000 CFUs per boot. Disinfection with a quaternary ammonium product sprayed through an electrostatic sprayer system effectively reduced the bacterial contamination on boots. Conclusions: PCFR recognizes firefighter boots as a critical vector of contamination between the environment encountered on emergency medical calls and the fire station environment and, as a result, has started a preliminary education campaign for agency firefighters regarding the need for regular boot disinfection. These efforts include regular submissions to the biweekly employee newsletter, as well as reminders on interoffice mailing envelopes (see example below) in hopes of increasing informal, self-directed boot cleaning and disinfection efforts. The next steps include verifying the effectiveness of specific disinfectant cleaners on boots; addressing logistical and practical barriers to routine cleaning and disinfection of boots; and developing, implementing, and evaluating a protocol for regular boot cleaning and disinfection.
Colonialism came late to northern Guatemala. The Spanish began to establish missions in the Peten Lakes region in the early 1700s, nearly 200 years after initial contact with the Mayas. Excavations in 2011–2012 at the Mission San Bernabé revealed European goods, nonnative animal species, and burial patterns that marked a new lifestyle. Who lived at the Mission San Bernabé, and where did they come from? The Spanish resettled indigenous populations to facilitate the colonization process; however, isotopic data are inconsistent with large population movements. Instead, strontium and oxygen isotope values in the tooth enamel and bones of individuals buried at the mission suggest a mostly local population. The data suggest in-migration from Belize, a region under nominal Spanish control, but with pre-Hispanic ties to the Peten. Changes did not come from migrants crossing a border; instead, the border itself moved and brought the colonial world to the Peten Mayas.
Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred >10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.
Disclosures: Scott Bergman reports a research grant from Merck.