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An ongoing challenge in understanding and treating personality disorders (PDs) is a significant heterogeneity in disorder expression, stemming from variability in underlying dynamic processes. These processes are commonly discussed in clinical settings, but are rarely empirically studied due to their personalized, temporal nature. The goal of the current study was to combine intensive longitudinal data collection with person-specific temporal network models to produce individualized symptom-level structures of personality pathology. These structures were then linked to traditional PD diagnoses and stress (to index daily functioning).
Using about 100 daily assessments of internalizing and externalizing domains underlying PDs (i.e. negative affect, detachment, impulsivity, hostility), a temporal network mapping approach (i.e. group iterative multiple model estimation) was used to create person-specific networks of the temporal relations among domains for 91 individuals (62.6% female) with a PD. Network characteristics were then associated with traditional PD symptomatology (controlling for mean domain levels) and with daily variation in clinically-relevant phenomena (i.e. stress).
Features of the person-specific networks predicted paranoid, borderline, narcissistic, and obsessive-PD symptom counts above average levels of the domains, in ways that align with clinical conceptualizations. They also predicted between-person variation in stress across days.
Relations among behavioral domains thought to underlie heterogeneity in PDs were indeed associated with traditional diagnostic constructs and with daily functioning (i.e. stress) in person-specific networks. Findings highlight the importance of leveraging data and models that capture person-specific, dynamic processes, and suggest that person-specific networks may have implications for precision medicine.
Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40–65 years). Accuracy and precision of EI were assessed using correlation and Bland–Altman analysis. Test–retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11–88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement −73 % to +68 %) in the first recall, 22 % (−61 % to +41 %) for average of first two, and 25 % (−60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.
We describe the design and deployment of GREENBURST, a commensal Fast Radio Burst (FRB) search system at the Green Bank Telescope. GREENBURST uses the dedicated L-band receiver tap to search over the 960–1 920 MHz frequency range for pulses with dispersion measures out to
. Due to its unique design, GREENBURST is capable of conducting searches for FRBs when the L-band receiver is not being used for scheduled observing. This makes it a sensitive single pixel detector capable of reaching deeper in the radio sky. While single pulses from Galactic pulsars and rotating radio transients will be detectable in our observations, and will form part of the database we archive, the primary goal is to detect and study FRBs. Based on recent determinations of the all-sky rate, we predict that the system will detect approximately one FRB for every 2–3 months of continuous operation. The high sensitivity of GREENBURST means that it will also be able to probe the slope of the FRB fluence distribution, which is currently uncertain in this observing band.
Following publication, errors were discovered in the y-axis labels of the electron and hole concentration plots in the following figure panels: figure 4c, figure 4d, figure 5c, figure 5d, figure 6c, figure 6d, figure 8c and figure 8d. The error does not affect the description, analysis or conclusions. The correct representation of the figure panels are shown here.
Introduction: Vasopressors are routinely utilized to treat systemic shock, a significant source of morbidity and mortality in the pediatric population. Local tissue ischemia has been classically implicated with peripheral use of these medications. However, peripheral administration (PVC) has theoretical benefits, and avoids many of the risks associated with central venous catheter (CVC) placement. There appears to be paucity of literature in pediatrics examining this subject. We conducted a systematic review investigating local tissue complications and extravasations of both PVC and CVC administration in the pediatric population. Specifically we examined the type of vasopressor used, the site used, the duration of the infusion, and finally the overall outcome for patients. Methods: A systematic search was conducted using PubMed, Embase, Cochrane, and CINAHL databases. Terms for IV administration, specific vasopressor use, complication of interest, and pediatric population were combined. We included studies that satisfied our predetermined criteria. All search results were imported into Covidence software where the primary author conducted an initial title and abstract review. Papers that met the pre-identified criteria were selected for full text review. Papers selected for full text review were independently reviewed by two of the authors. Agreement between the authors was measured utilizing a κ statistic. Results: Our search yielded 14784 results, of which 237 were assessed for full text review. The κ between the authors is pending. 13 studies were selected for final inclusion. There were 14 patients with 15 total events. 13 were from PVC use while 2 occurred with CVC's. 11 of the 13 complications associated with PVC administration occurred through extravasation, with 2 events from local ischemia. 9 children were administered dopamine, 1 norepinephrine, and 14 were on multiple vasopressors. 3/13 events were “proximal” or occurring at or above the AC or popliteal fossa while 10/13 events were “distal”. The average time to ischemic injury or extravasation peripherally was 56.1 hours with a range of 1.5 to 360 hours. 9 of the total patients did not have any long-term sequelae. One patient had toe amputations, while two others died because of illness. One CVC patient died as a result extravasation leading to asphyxiation. Conclusion: There is a lack of significant literature reporting serious adverse events related to peripheral or central administration of vasopressors in the pediatric population.
Mini-sabbaticals are formal short-term training and educational experiences away from an investigator’s home research unit. These may include rotations with other research units and externships at government research or regulatory agencies, industry and non-profit programs, and training and/or intensive educational programs. The National Institutes of Health have been encouraging training institutions to consider offering mini-sabbaticals, but given the newness of the concept, limited data are available to guide the implementation of mini-sabbatical programs. In this paper, we review the history of sabbaticals and mini-sabbaticals, report the results of surveys we performed to ascertain the use of mini-sabbaticals at Clinical and Translational Science Award hubs, and consider best practice recommendations for institutions seeking to establish formal mini-sabbatical programs.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.
Background: NURTURE (NCT02386553) is an ongoing open-label single-arm efficacy/safety study of intrathecal nusinersen in infants who initiate treatment in a presymptomatic stage of spinal muscular atrophy (SMA). Methods: Enrolled infants were age ≤6 weeks at first dose, clinically presymptomatic, had genetically diagnosed SMA, and 2 or 3 copies of SMN2. Primary endpoint is time to death or respiratory intervention (≥6 hours/day continuously for ≥7 days or tracheostomy). Results: As of July 5, 2017, 25 infants (2 copies SMN2, n=15;3 copies, n=10) were enrolled. All infants were alive. Two infants (both with 2 copies SMN2) required respiratory intervention (but not tracheostomy or permanent ventilation) during an acute, reversible viral infection and thus met the primary -endpoint. At last visit, 22/24 (92%) infants had achieved WHO motor milestones sitting without support and 8/16 (50%;2 SMN2, n=3/11;3 SMN2, n=5/5) on study >13 months achieved walking alone. AEs were reported in 24/25 (96%) infants; most 20/25 (80%) had AEs that were mild/moderate in severity; 9 had serious AEs. Four infants had an AE possibly related to study drug, which resolved despite continued treatment. No new safety concerns were identified. Conclusions: Nusinersen continued to benefit infants who initiated treatment in a presymptomatic stage of SMA.
To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.
Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.
We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.
Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.
Increasing evidence suggests that the presence of mobile ions in perovskite solar cells (PSCs) can cause a current–voltage curve hysteresis. Steady state and transient current–voltage characteristics of a planar metal halide CH3NH3PbI3 PSC are analysed with a drift-diffusion model that accounts for both charge transport and ion vacancy motion. The high ion vacancy density within the perovskite layer gives rise to narrow Debye layers (typical width ~2 nm), adjacent to the interfaces with the transport layers, over which large drops in the electric potential occur and in which significant charge is stored. Large disparities between (I) the width of the Debye layers and that of the perovskite layer (~600 nm) and (II) the ion vacancy density and the charge carrier densities motivate an asymptotic approach to solving the model, while the stiffness of the equations renders standard solution methods unreliable. We derive a simplified surface polarisation model in which the slow ion dynamics are replaced by interfacial (non-linear) capacitances at the perovskite interfaces. Favourable comparison is made between the results of the asymptotic approach and numerical solutions for a realistic cell over a wide range of operating conditions of practical interest.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
There is currently limited experience in the initiation and maintenance of clozapine for treatment-resistant psychosis in adults with established structural heart disease. These complex patients require close supervision and liaison between colleagues. Here we present the successful experience of treating one such patient within our service and describe a monitoring plan to ensure that these treatments can be provided both safely and effectively.
A 36-year-old man with treatment-resistant schizophrenia and known hypertrophic cardiomyopathy (HCM) was admitted to a specialist unit for a trial of clozapine. His psychiatric illness was characterised by multimodal hallucinations and delusions combined with low mood and poor motivation. The diagnosis of HCM was made 3 years previously following a routine electrocardiogram (ECG), and he had remained asymptomatic throughout this time; there were concerns about the risk of initiating clozapine given his pre-existing cardiac condition. Baseline investigations were performed as per local guidelines prior to commencing clozapine; these were within normal limits other than a mildly raised troponin level of 54 ng/L (normal <16 ng/L), which was attributed to the HCM. In addition, baseline transthoracic echocardiography (TTE) was performed which showed no change in the structural heart disease in comparison with previous TTEs.
Clozapine was started at 12.5 mg daily and up-titrated to 150 mg twice daily over 14 days as per our institute's guidelines. The patient was monitored with regular testing of troponins, inflammatory markers and ECG. On day 18, the troponin level increased to 1371 ng/L. Creatine kinase and inflammatory markers remained stable. No changes in ECG or TTE were noted and the patient remained clinically asymptomatic. Cardiology opinion was sought and reported that the finding of an isolated elevated troponin was likely to reflect a ‘troponin leak’ in the context of increased cardiac muscle mass associated with HCM. In the absence of any clinical compromise, it was not felt to be of concern. Clozapine was continued with good effect on mental state. Troponin levels gradually reduced and the patient remained well.
While multiple cases of clozapine-induced cardiotoxicity have been reported in the literature, its implications for pre-existing structural disease are unclear. This case report suggests that clozapine can be safely introduced in pre-existing HCM, explores strategies for monitoring and highlights the importance of liaising with experienced cardiologists.
The Qin jiandu yanjiu 秦簡牘研究 (Research on Qin strips) book series, edited by Chen Wei 陳偉, presents important findings from the “Comprehensive Arrangement and Study of the Qin Bamboo Slip Manuscripts” research project. Organized thematically into five volumes, detailed case studies on newly unearthed Qin texts address issues in institutional history, law, geography, mantic arts, and linguistics. The Qin jiandu yanjiu series supplements the Qin jiandu heji 秦簡牘合集 (Corpus of Qin documents written on bamboo and wood) and Liye Qin jiandu jiaoshi (diyi juan) 里耶秦簡牘校釋(第一卷) (Annotated transcriptions of the Liye Qin strips (volume one)) reference works, and indirectly serves as a state of the field for Qin manuscript studies.
In the United States, cannabis accessibility has continued to rise as the perception of its harmfulness has decreased. Only about 30% of regular cannabis users develop cannabis use disorder (CUD), but it is unclear if individuals who use cannabis regularly without ever developing CUD experience notable psychosocial impairment across the lifespan. Therefore, psychosocial functioning was compared across regular cannabis users with or without CUD and a non-user control group during adolescence (age 17; early risk) and young adulthood (ages 18–25; peak CUD prevalence).
Weekly cannabis users with CUD (n = 311), weekly users without CUD (n = 111), and non-users (n = 996) were identified in the Minnesota Twin Family Study. Groups were compared on alcohol and illicit drug use, psychiatric problems, personality, and social functioning at age 17 and from ages 18 to 25. Self-reported cannabis use and problem use were independently verified using co-twin informant report.
In both adolescence and young adulthood, non-CUD users reported significantly higher levels of substance use problems and externalizing behaviors than non-users, but lower levels than CUD users. High agreement between self- and co-twin informant reports confirmed the validity of self-reported cannabis use problems.
Even in the absence of CUD, regular cannabis use was associated with psychosocial impairment in adolescence and young adulthood. However, regular users with CUD endorsed especially high psychiatric comorbidity and psychosocial impairment. The need for early prevention and intervention – regardless of CUD status – was highlighted by the presence of these patterns in adolescence.