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Sensorimotor gating is experimentally operationalized by the prepulse inhibition (PPI) of the startle response (SR). Previous studies suggest high test-retest reliability of PPI and potential correlation with working memory (WM). Here, we aimed to validate and extend the test-retest reliability of PPI in healthy humans and its correlation with WM performance.
We applied an acoustic startle PPI paradigm with four different prepulse intensities (64, 68, 72 and 76 dB) and two different WM tasks [n-back, change detection task (CDT)] in a group of 26 healthy adults (final sample size n = 23). To assess test-retest reliability, we performed all tests on two separate days ~27 days (range: 21–32 days) apart.
We were able to confirm high test-retest reliability of the PPI with a mean intraclass correlation (ICC) of > 0.80 and significant positive correlation of PPI with n-back but not with CDT performance. Detailed analysis showed that PPI across all prepulse intensities significantly correlated with both the 2-back and 0-back conditions, suggesting regulation by cross-conditional processes (e.g. attention). However, when removing the 0-back component from the 2-back data, we found a specific and significant correlation with WM for the 76-dB PPI condition.
With the present study, we were able to confirm the high test-retest reliability of the PPI in humans and could validate and expand on its correlation with WM performance.
In this survey of 41 hospitals, 18 (72%) of 25 respondents reporting utilization of National Healthcare Safety Network resources demonstrated accurate central-line–associated bloodstream infection reporting compared to 6 (38%) of 16 without utilization (adjusted odds ratio, 5.37; 95% confidence interval, 1.16–24.8). Adherence to standard definitions is essential for consistent reporting across healthcare facilities.
Posttraumatic stress symptoms (PTSS) are common following traumatic stress exposure (TSE). Identification of individuals with PTSS risk in the early aftermath of TSE is important to enable targeted administration of preventive interventions. In this study, we used baseline survey data from two prospective cohort studies to identify the most influential predictors of substantial PTSS.
Self-identifying black and white American women and men (n = 1546) presenting to one of 16 emergency departments (EDs) within 24 h of motor vehicle collision (MVC) TSE were enrolled. Individuals with substantial PTSS (⩾33, Impact of Events Scale – Revised) 6 months after MVC were identified via follow-up questionnaire. Sociodemographic, pain, general health, event, and psychological/cognitive characteristics were collected in the ED and used in prediction modeling. Ensemble learning methods and Monte Carlo cross-validation were used for feature selection and to determine prediction accuracy. External validation was performed on a hold-out sample (30% of total sample).
Twenty-five percent (n = 394) of individuals reported PTSS 6 months following MVC. Regularized linear regression was the top performing learning method. The top 30 factors together showed good reliability in predicting PTSS in the external sample (Area under the curve = 0.79 ± 0.002). Top predictors included acute pain severity, recovery expectations, socioeconomic status, self-reported race, and psychological symptoms.
These analyses add to a growing literature indicating that influential predictors of PTSS can be identified and risk for future PTSS estimated from characteristics easily available/assessable at the time of ED presentation following TSE.
In May of 2018, PulseNet, the national molecular subtyping network for enteric pathogens, detected a multistate cluster of illnesses caused by an uncommon molecular subtype of Salmonella serovar Mbandaka. A case was defined as an illness in a person infected with the outbreak strain of Salmonella Mbandaka with illness onset on or after 3 March 2018 and before 1 September 2018. One-hundred thirty-six cases from 36 states were identified; 35 hospitalisations and no deaths were reported. Ill people ranged in age from <1 year to 95 years (median: 57 years). When standardised questionnaires did not generate a strong hypothesis, opened-ended interviews were performed. Sixty-three of 84 (75%) ultimately reported consuming or possibly consuming a specific sweetened puffed wheat cereal in the week before illness onset. Environmental sampling performed at the cereal manufacturing facility yielded the outbreak strain. The outbreak strain was also isolated from open cereal samples from ill people's homes and from a sealed retail sample. Due to these findings, the brand owner of the product issued a voluntary recall of the cereal on 14 June 2018. Additional investigation of the manufacturing facility identified persistent environmental contamination with Salmonella Mbandaka that was closely genetically related to other isolates in the outbreak. This investigation highlights the ability of Salmonella to survive in low-moisture environments, and the potential for prolonged outbreaks linked to products with long shelf lives and large distribution areas.
Research on complications with peripherally inserted central catheter (PICC) lines that are placed for the treatment of prosthetic joint infection (PJI) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) is scarce. We investigated the timing, frequency, and risk factors for PICC complications during treatment of PJI after THA and TKA.
We retrospectively queried an institutional database for THA and TKA patients from January 2015 through December 2020 that developed a PJI and required PICC placement at an academic, tertiary-care referral center.
The study included 889 patients (48.3% female) with a mean age of 64.6 years (range, 18.7–95.2) who underwent 435 THAs and 454 TKAs that were revised for PJI. The cohort had 275 90-day ED visits (30.9%), and 51 (18.5%) were PICC related. The average time from discharge to PICC ED visit was 26.2 days (range, 0.3–89.4). The most common reasons for a 90-day ED visit were issues related to the joint replacement or wound site (musculoskeletal or MSK; n = 116, 42.2%) and PICC complaints (n = 51, 18.5%). A multivariable logistic regression demonstrated that non-White race (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.24–4.04; P = .007) and younger age (OR, 0.98; 95% CI, 0.95–1.00; P = .035) were associated with PICC-related ED visits. Malposition/readjustment (41.2%) and occlusion (35.3%) were the most common PICC complications leading to ED presentation.
PICC complications are common after PJI treatment, accounting for nearly 20% of 90-day ED visits.
Mixed flora in urine cultures usually occur due to preanalytic contamination. In our outpatient urology clinic, we detected a high prevalence of mixed flora (46.2%), which was associated with female sex and older age. Patient education did not influence the rate of mixed flora. Future efforts should target high-risk patients.
To investigate the effectiveness of a daily attestation system used by employees of a multi-institutional academic medical center, which comprised of symptom-screening, self-referrals to the Occupational Health Services team, and/or a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test.
We conducted a retrospective cohort study of all employee attestations and SARS-CoV-2 tests performed between March and June 2020.
A large multi-institutional academic medical center, including both inpatient and ambulatory settings.
All employees who worked at the study site.
Data were combined from the attestation system (COVIDPass), the employee database, and the electronic health records and were analyzed using descriptive statistics including χ2, Wilcoxon, and Kruskal-Wallis tests. We investigated whether an association existed between symptomatic attestations by the employees and the employee testing positive for SARS-CoV-2.
After data linkage and cleaning, there were 2,117,298 attestations submitted by 65,422 employees between March and June 2020. Most attestations were asymptomatic (99.9%). The most commonly reported symptoms were sore throat (n = 910), runny nose (n = 637), and cough (n = 570). Among the 2,026 employees who ever attested that they were symptomatic, 905 employees were tested within 14 days of a symptomatic attestation, and 114 (13%) of these tests were positive. The most common symptoms associated with a positive SARS-CoV-2 test were anosmia (23% vs 4%) and fever (46% vs 19%).
Daily symptom attestations among healthcare workers identified a handful of employees with COVID-19. Although the number of positive tests was low, attestations may help keep unwell employees off campus to prevent transmissions.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.
In April 2019, the U.S. Fish and Wildlife Service (USFWS) released its recovery plan for the jaguar Panthera onca after several decades of discussion, litigation and controversy about the status of the species in the USA. The USFWS estimated that potential habitat, south of the Interstate-10 highway in Arizona and New Mexico, had a carrying capacity of c. six jaguars, and so focused its recovery programme on areas south of the USA–Mexico border. Here we present a systematic review of the modelling and assessment efforts over the last 25 years, with a focus on areas north of Interstate-10 in Arizona and New Mexico, outside the recovery unit considered by the USFWS. Despite differences in data inputs, methods, and analytical extent, the nine previous studies found support for potential suitable jaguar habitat in the central mountain ranges of Arizona and New Mexico. Applying slightly modified versions of the USFWS model and recalculating an Arizona-focused model over both states provided additional confirmation. Extending the area of consideration also substantially raised the carrying capacity of habitats in Arizona and New Mexico, from six to 90 or 151 adult jaguars, using the modified USFWS models. This review demonstrates the crucial ways in which choosing the extent of analysis influences the conclusions of a conservation plan. More importantly, it opens a new opportunity for jaguar conservation in North America that could help address threats from habitat losses, climate change and border infrastructure.
On January 29, 2020, a total of 195 US citizens were evacuated from the coronavirus disease 2019 (COVID-19) epidemic in Wuhan, China, to March Air Reserve Base in Riverside, California, and entered the first federally mandated quarantine in over 50 years. With less than 1-d notice, a multi-disciplinary team from Riverside County and Riverside University Health System in conjunction with local and federal agencies established on-site 24-h medical care and behavioral health support. This report details the coordinated efforts by multiple teams that took place to provide care for the passengers and to support the surrounding community.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting <3 hours from stroke onset and achieving ultra-early reperfusion (<45 minutes from CTP) are reported. CTP thresholds that predict follow-up infarction vary based on time to reperfusion: Tmax >20 to 23 seconds and cerebral blood flow <5 to 7 ml/min−1/(100 g)−1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Belle Époque Belgium recorded an unprecedented trade boom. Exploiting a new granular trade dataset, we find that the number of products delivered abroad and destinations serviced more than doubled in less than 40 years. To explain this remarkable achievement, we study the relationship between trade costs and the intensive and extensive margins of trade. The establishment of a foreign diplomatic network that lowered beachhead costs and enabled the entry of new products was an essential fact of the trade boom. Interestingly, the expansion in trade in certain sectors did not translate into faster productivity growth. We offer some explanations.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.