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Emergency Medical Services (EMS) providers are trained to place endotracheal tubes (ETTs) in the prehospital setting when indicated. Endotracheal tube cuffs are traditionally inflated with 10cc of air to provide adequate seal against the tracheal lumen. There is literature suggesting that many ETTs are inflated well beyond the accepted safe pressures of 20-30cmH2O, leading to potential complications including ischemia, necrosis, scarring, and stenosis of the tracheal wall. Currently, EMS providers do not routinely check ETT cuff pressures. It was hypothesized that the average ETT cuff pressure of patients arriving at the study site who were intubated by EMS exceeds the safe pressure range of 20-30cmH2O.
While ETT cuff inflation is necessary to close the respiratory system, thus preventing air leaks and aspiration, there is evidence to suggest that over-inflated ETT cuffs can cause long-term complications. The purpose of this study is to characterize the cuff pressures of ETTs placed by EMS providers.
This project was a single center, prospective observational study. Endotracheal tube cuff pressures were measured and recorded for adult patients intubated by EMS providers prior to arrival at a large, urban, tertiary care center over a nine-month period. All data were collected by respiratory therapists utilizing a cuff pressure measurement device which had a detectable range of 0-100cmH2O and was designed as a syringe. Results including basic patient demographics, cuff pressure, tube size, and EMS service were recorded.
In total, 45 measurements from six EMS services were included with ETT sizes ranging from 6.5-8.0mm. Mean patient age was 52.2 years (67.7% male). Mean cuff pressure was 81.8cmH2O with a range of 15 to 100 and a median of 100. The mode was 100cmH2O; 40 out of 45 (88.9%) cuff pressures were above 30cmH2O. Linear regression showed no correlation between age and ETT cuff pressure or between ETT size and cuff pressure. Two-tailed T tests did not show a significant difference in the mean cuff pressure between female versus male patients.
An overwhelming majority of prehospital intubations are associated with elevated cuff pressures, and cuff pressure monitoring education is indicated to address this phenomenon.
The Scarr–Rowe effect is a gene × environment interaction, which is characterized by a negative association between exposure to low socioeconomic status (SES) environments and the additive heritability of cognitive ability. Utilizing a polygenic score for educational attainment (EA3), it was found that the two-way interaction between EA3 and parental educational attainment (EA; used as a proxy for parental SES) was a significant positive predictor of participants’ composite cognitive ability (IQ) score (β = .018, SE = .008, p = .028) after controlling hierarchically for the direct effects of (population-stratification-controlled) EA3, parental EA, and 20 distinct interaction terms (10 involving the interactions between the principal components [PCs] and EA3, and 10 involving the interaction between the PCs and parental EA). The presence of this interaction is consistent with the Scarr–Rowe effect, as the expressivity of EA3 on cognitive ability increases with increasing parental EA. No statistically significant sex differences in the effect magnitudes were found, although the effect was significantly present in the female but not male sample.
The essential liver endocrine and exocrine functions require a precise spatial arrangement of the repeated hepatic lobule consisting of the central vein, portal vein, hepatic artery, intrahepatic bile duct system, and hepatocyte zonation. This allows (1) blood to be carried through the liver parenchyma and sampled by all hepatocytes, (2) hepatocytes to uptake metabolites and toxins from the blood for metabolizing and detoxification from their basal sinusoidal side, and (3) hepatocytes to produce and secrete bile from their apical canalicular side to be carried out of the liver through the biliary (i.e., intrahepatic bile duct) system composed of biliary epithelial cells (i.e., cholangiocytes).
The Real Time Mesoscale Analysis (RTMA), a two-dimensional variational analysis algorithm, is used to provide hourly analyses of surface sensible weather elements for situational awareness at spatial resolutions of 3 km over Alaska. In this work we focus on the analysis of horizontal visibility in Alaska, which is a region prone to weather related aviation accidents that are in part due to a relatively sparse observation network. In this study we evaluate the impact of assimilating estimates of horizontal visibility derived from a novel network of web cameras in Alaska with the RTMA. Results suggest that the web camera-derived estimates of visibility can capture low visibility conditions and have the potential to improve the RTMA visibility analysis under conditions of low instrument flight rules and instrument flight rules.
Systemic ventricular end-diastolic pressure is important in patients with single ventricle heart disease. Predictors of an elevated systemic ventricular end-diastolic pressure prior to bidirectional Glenn operation have been incompletely identified.
All patients who underwent bidirectional Glenn operation operation at our centre between January 2007 and March 2017 were retrospectively identified and patient variables were extracted. For patients who had undergone Fontan operation at the time of this study, post-Fontan patient variables were also extracted.
One-hundred patients were included with a median age at pre-bidirectional Glenn operation catheterisation of 4.5 months. In total, 71 (71%) patients had a systemic right ventricle. At the pre-bidirectional Glenn operation catheterisation, the mean systemic ventricular end-diastolic pressure was higher amongst those with systemic right ventricle compared to left ventricle (9.1 mmHg ± 2.1 versus 7.7 ± 2.7 mmHg, p < 0.01). On univariate analysis, pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01), history of recoarctation (p = 0.03), history of Norwood operation (p = 0.04), and ventricular systolic pressure (p < 0.01). On multivariate analysis, systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01) and ventricular systolic pressure (p < 0.01). Amongst those who had undergone Fontan operation at the time of study (n = 49), those with a higher pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure were more likely to have experienced death, transplantation, or listed for transplantation (p = 0.02) and more likely to have had heart failure symptoms (p = 0.04) at a mean time from Fontan of 5.2 years ± 1.3.
In patients undergoing bidirectional Glenn operation operation, the volume-loaded, pre-bidirectional Glenn operation state may expose diastolic dysfunction that has prognostic value.
Kinetoplastid parasites are responsible for both human and animal diseases across the globe where they have a great impact on health and economic well-being. Many species and life cycle stages are difficult to study due to limitations in isolation and culture, as well as to their existence as heterogeneous populations in hosts and vectors. Single-cell transcriptomics (scRNA-seq) has the capacity to overcome many of these difficulties, and can be leveraged to disentangle heterogeneous populations, highlight genes crucial for propagation through the life cycle, and enable detailed analysis of host–parasite interactions. Here, we provide a review of studies that have applied scRNA-seq to protozoan parasites so far. In addition, we provide an overview of sample preparation and technology choice considerations when planning scRNA-seq experiments, as well as challenges faced when analysing the large amounts of data generated. Finally, we highlight areas of kinetoplastid research that could benefit from scRNA-seq technologies.
A retrospective study was conducted to describe the impact of a molecular assay to detect the most common carbapenemase genes in carbapenem-resistant Enterobacterales isolates recovered in culture. Carbapenemases were detected in 69% of isolates, and assay results guided treatment modifications or epidemiologic investigation in 20% and 4% of cases, respectively.
It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults.
Lipids were measured at baseline (1985–1986; age: 18–30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes.
There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101–129 mg/dL, 130–159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV.
Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.
Among 353 healthcare personnel in a longitudinal cohort in four hospitals in Atlanta, GA (May-June 2020), 23 (6.5%) had SARS-CoV-2 antibodies. Spending >50% of a typical shift at bedside (OR 3.4, 95% CI: 1.2–10.5) and Black race (OR 8.4, 95% CI: 2.7–27.4) were associated with SARS-CoV-2 seropositivity.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to COVID-19 with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplemental materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
The direct carbonate procedure for accelerator mass spectrometry radiocarbon (AMS 14C) dating of submilligram samples of biogenic carbonate without graphitization is becoming widely used in a variety of studies. We compare the results of 153 paired direct carbonate and standard graphite 14C determinations on single specimens of an assortment of biogenic carbonates. A reduced major axis regression shows a strong relationship between direct carbonate and graphite percent Modern Carbon (pMC) values (m = 0.996; 95% CI [0.991–1.001]). An analysis of differences and a 95% confidence interval on pMC values reveals that there is no significant difference between direct carbonate and graphite pMC values for 76% of analyzed specimens, although variation in direct carbonate pMC is underestimated. The difference between the two methods is typically within 2 pMC, with 61% of direct carbonate pMC measurements being higher than their paired graphite counterpart. Of the 36 specimens that did yield significant differences, all but three missed the 95% significance threshold by 1.2 pMC or less. These results show that direct carbonate 14C dating of biogenic carbonates is a cost-effective and efficient complement to standard graphite 14C dating.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
Although first responders (FRs) represent a high-risk group for exposure, little information is available regarding their risk of coronavirus disease 2019 (COVID-19) infection. The purpose of the current study was to determine the serological prevalence of past COVID-19 infection in a cohort of municipal law enforcement (LE) and firefighters (FFs).
Descriptive analysis of a de-identified data reporting Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) immunoglobulin G (IgG), or COR2G, serology results for municipal FRs. As part of the serology process, FRs were surveyed for COVID-19-like symptoms since February 2020 and asked to report any prior COVID-19 nasal swab testing. Descriptive statistics and two-sided Chi Square tests with Yates correction were used to compare groups.
Of 318 FRs, 225 (80.2%) underwent serology testing (LE: 163/207 [78.7%]; FF: 92/111 [82.9%]). The prevalence of positive serology for all FRs tested was 3/255 (1.2%). Two LE (1.2%) and one FF (1.1%) had positive serology (P = 1.0). Two hundred and twenty-four FRs responded to a survey regarding prior symptoms and testing. Fifty-eight (25.9%) FRs (44 LE; 14 FFs) reported the presence of COVID-19-like symptoms. Of these, only nine (15.5%) received reverse transcriptase – polymerase chain reaction (RT-PCR) testing; none were positive. Two of the three FRs with positive serology reported no COVID-19-like symptoms and none of these responders had received prior nasal RT-PCR swabs. The overall community positive RT-PCR rate was 0.36%, representing a three-fold higher rate of positive seroprevalence amongst FRs compared with the general population (P = .07).
Amongst a cohort of municipal FRs with low community COVID-19 prevalence, the seroprevalence of SARS-CoV-19 IgG Ab was three-fold greater than the general community. Two-thirds of positive FRs reported a lack of symptoms. Only 15.5% of FRs with COVID-19-like symptoms received RT-PCR testing. In addition to workplace control measures, increased testing availability to FRs is critical in limiting infection spread and ensuring response capability.
In this essay, we describe the overlapping phenomena of new legal hubs (NLHs), international commercial courts, and arbitral courts. We survey their impact on the law and geopolitics of international commercial dispute resolution, identifying key issues these new dispute resolution institutions raise. While the rise of international commercial courts spans authoritarian and liberal states, Western and Asian states, common law and civil law traditions, it also highlights and builds upon regional differences. We question the assumption that the establishment of new courts is always consistent with an increase in the rule of law, particularly in non-democratic states. We close with thoughts about the potential influence and future role of these institutions. Some of the procedural innovations discussed here may lead to shifts in international commercial dispute resolution for years to come, but the question of whether there is sufficient demand for these new institutions lingers.
An early economic evaluation to inform the translation into clinical practice of a spectroscopic liquid biopsy for the detection of brain cancer. Two specific aims are (1) to update an existing economic model with results from a prospective study of diagnostic accuracy and (2) to explore the potential of brain tumor-type predictions to affect patient outcomes and healthcare costs.
A cost-effectiveness analysis from a UK NHS perspective of the use of spectroscopic liquid biopsy in primary and secondary care settings, as well as a cost–consequence analysis of the addition of tumor-type predictions was conducted. Decision tree models were constructed to represent simplified diagnostic pathways. Test diagnostic accuracy parameters were based on a prospective validation study. Four price points (GBP 50-200, EUR 57-228) for the test were considered.
In both settings, the use of liquid biopsy produced QALY gains. In primary care, at test costs below GBP 100 (EUR 114), testing was cost saving. At GBP 100 (EUR 114) per test, the ICER was GBP 13,279 (EUR 15,145), whereas at GBP 200 (EUR 228), the ICER was GBP 78,300 (EUR 89,301). In secondary care, the ICER ranged from GBP 11,360 (EUR 12,956) to GBP 43,870 (EUR 50,034) across the range of test costs.
The results demonstrate the potential for the technology to be cost-effective in both primary and secondary care settings. Additional studies of test use in routine primary care practice are needed to resolve the remaining issues of uncertainty—prevalence in this patient population and referral behavior.
Precise measurements of the calcium (Ca) isotopes have provided constraints on Ca cycling at global and local scales, and quantified rates of carbonate diagenesis in marine sedimentary systems. Key to applying Ca isotopes as a geochemical tracer of Ca cycling, carbonate (bio)mineralization, and diagenesis is an understanding of the impact of multiple factors potentially impacting Ca isotopes in the rock record. These factors include variations in stable isotopic fractionation factors, the influence of local-scale Ca cycling on Ca isotopic gradients in carbonate settings, carbonate dissolution and reprecipitation, and the relationship between the Ca isotopic composition of seawater and mineral phases that record the secular evolution of seawater chemistry.
To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.
The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).
Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.
A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.
We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.