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Adolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of fluoxetine on emotional reactivity and cognitive reappraisal in adolescent depression.
Thirty-one adolescents with MDD were randomised to acute fluoxetine (10 mg) or placebo. Seventeen healthy adolescents were also recruited but did not receive any treatment for ethical reasons. During functional magnetic resonance imaging (fMRI), participants viewed aversive images and were asked to either experience naturally the emotional state elicited (‘Maintain’) or to reinterpret the content of the pictures to reduce negative affect (‘Reappraise’). Significant activations were identified using whole-brain analysis.
No significant group differences were seen when comparing Reappraise and Maintain conditions. However, when compared to healthy controls, depressed adolescents on placebo showed reduced visual activation to aversive pictures irrespective of the condition. The depressed adolescent group on fluoxetine showed the opposite pattern, i.e. increased visuo-cerebellar activity in response to aversive pictures, when compared to depressed adolescents on placebo.
These data suggest that depression in adolescence may be associated with reduced visual processing of aversive imagery and that fluoxetine may act to reduce avoidance of such cues. This could reflect a key mechanism whereby depressed adolescents engage with negative cues previously avoided. Future research combining fMRI with eye-tracking is nonetheless needed to further clarify these effects.
The transfer rate for patients from an Alternate Care Site (ACS) back to a hospital may serve as a metric of appropriate patient selection and the ability of an ACS to treat moderate to severely ill patients accepted from overwhelmed health-care systems. During the coronavirus infectious disease 2019 (COVID-19) pandemic, hospitals worldwide experienced acute surges of patients presenting with acute respiratory failure.
An ACS in Imperial County, California was re-established in November 2020 to help decompress 2 local hospitals experiencing surges of COVID-19 cases. The patients treated often had multiple comorbid illnesses and required a median supplemental oxygen of 3 L/min (LPM) on admission. Numerous interventions were initiated during a 2-wk period to improve clinical care delivery.
The objectives of this retrospective observational study are to evaluate the impact of these clinical and staff interventions at an ACS on the transfer rate and to provide issues to consider for future ACS sites managing COVID-19 patients.
The data suggest that continuous, real-time process-improvement interventions helped reduce the transfer rate back to hospitals from 36.7% to 14.5% and that an ACS is a viable option for managing symptomatic COVID-19 positive patients requiring hospital-level care when hospitals are overburdened.
The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
A system for examination of the peripheral nerves of the upper limb is described in this chapter. This includes the ulnar, median, radial, axillary and musculocutaneous nerves. The steps are inspection followed by a screen test to decide if the lesion is likely to be radial, median or ulnar. Then the nerve is examined in more detail by testing sensation and movement in relation to that nerve. Provocation tests are performed if necessary. This chapter also describes nerve compression as a result of thoracic outlet syndrome, as this may be a differential diagnosis. In the ‘Advanced corner’ Tinel’s sign and Valleix phenomenon as well as ‘double crush’ are described.
Clinical cases covering the spectrum of upper limb pathology are presented here. In the hand, these include congenital hand deficiencies, Dupuytren’s disease, rheumatoid disease, nerve lesions and tendon transfers. In the elbow, this includes osteoarthritis and in the shoulder, massive cuff tear, scapula winging and painful shoulder arthroplasty. Clinical examination findings for each of the cases are highlighted.
OBJECTIVES/GOALS: In triple negative breast cancer (TNBC), obesity is associated with poor outcomes. Adipose stem cells (ASCs) from obese patients (obASCs) secrete higher levels of adipokines compared to ASCs from lean individuals. Leptin, one of these adipokines, has been implicated in many cancers. This study seeks to examine the role of leptin signaling in TNBC. METHODS/STUDY POPULATION: Previous work in conjunction with a collaborating lab has shown that leptin signaling promotes metastasis and increased expression of epithelial-mesenchymal transition (EMT) markers in triple negative breast cancer cell lines. This project expands upon this work through using both patient-derived cell lines and and patient-derived xenografts (PDX), and examines the role of leptin signaling both in vitro and in vivo. To determine the effects of obesity upon a PDX model of TNBC, a high fat diet was used to induce obesity in vivo. A pharmacological inhibitor of the leptin receptor was used to test the requirement for leptin signaling both in vivo and in vitro. RESULTS/ANTICIPATED RESULTS: Exposure to conditioned media harvested from obASCs increased the percentage of TNBC cells that expressed cancer stem cell markers, whereas exposure to an inhibitor of the leptin receptor decreased the percentage of cells with cancer stem cell markers. PDX tumors implanted into mice with diet-induced obesity had an increased volume compared to tumors implanted into lean controls. Further analysis will be conducted on metastasis, circulating tumor cells, and survival in both lean and obese mice. DISCUSSION/SIGNIFICANCE: Understanding the complex signaling events in the obese tumor microenvironment is essential, as these molecular differences may contribute to different outcomes for obese and lean individuals with triple negative breast cancer. Therefore, study of the crosstalk between obASCs and TNBC cells is critical.
This Element reviews literature on the physiological influences of music during perception and action. It outlines how acoustic features of music influence physiological responses during passive listening, with an emphasis on comparisons of analytical approaches. It then considers specific behavioural contexts in which physiological responses to music impact perception and performance. First, it describes physiological responses to music that evoke an emotional reaction in listeners. Second, it delineates how music influences physiology during music performance and exercise. Finally, it discusses the role of music perception in pain, focusing on medical procedures and laboratory-induced pain with infants and adults.
Interlocking directorates can encourage innovation, cooperation, and adherence to best practices or can contribute to collusion, corruption, and the stagnation of ideas. Research has identified the contingent nature of director networks, with outcomes dependent on the nature of the tie; the firms and individuals involved; and the institutional, sociopolitical, and cultural context. Distinguishing between helpful and harmful interlocks thus requires understanding the foundations on which they were built. This article is the first systematic, longitudinal analysis of the antecedents of interlocking directorates in Australia, complementing substantial international efforts to understand and compare director networks across the twentieth century. The network has been characterized by a relatively consistent long-run level of connection but substantial variation in the causes of interlocks. The director network in Australia has responded to the pragmatics of the board member occupation, with corporate governance regulations, the progress of the professions, banking and prudential practices, and the form of large organizations encouraging ties that were built on professional expertise and geographic proximity. These findings are important for policy makers, regulatory bodies, and scholars, highlighting the importance of understanding the contextual foundations of interlocks when assessing their potential for harm.
The objective was to use bibliometric analysis to create an infographic of motor unit number estimation methods over the past 50 years. The original method was published in 1971, but secondary and tertiary waves of research using alternative methods occurred in the early 2000s and a decade later. A metric of influence was used to determine if different methods had clear peaks of use over the past 50 years. While the original method continues to register influence, the MUNIX method introduced in 2004 stands out as the most influential method to estimate the innervation status of skeletal muscles.
Since 2008, academics and policymakers have frequently debated why bond rating agencies such as Moody's, S&P, and Fitch enjoy considerable power and influence. The 2008 financial crisis focused our attention on the bond rating agencies that had previously categorized mortgage-backed securities as investment grade. Scholars have attributed the power enjoyed by the rating agencies to regulations that confer a privileged status on those agencies that are designated as nationally recognized statistical rating organizations (NRSROs) by the U.S. Securities and Exchange Commission (SEC). While these authors mention in passing that the relevant regulation went into effect in 1975, none has conducted archival research to examine why this regulation was introduced at that time. This article is the first historical investigation of the creation of this crucial regulation, which entrenched the concept of the NRSRO in federal securities law. It shows that the SEC mandated the use of NRSRO-created ratings even though SEC officials vigorously debated whether it was wise for the commission to endorse ratings produced by agencies that operate on the basis of the controversial issuer-pay model. This article contributes to our understanding of the SEC's role in the development of the distinctive features of American capitalism.
Bell's palsy is a lower motor neurone facial weakness of unknown aetiology, although reactivation of a virus within the facial nerve has been proposed.
A prospective study was conducted of Bell's palsy cases presenting to our paediatric ENT unit over a 19-week period, from February to June 2020. Patients were invited for severe acute respiratory syndrome coronavirus-2 antibody testing. A text-message questionnaire was sent to other ENT centres to determine their observational experience.
During the study period, 17 children presented with Bell's palsy, compared with only 3 children in the same time period in the previous year (p < 0.0001). Five patients underwent severe acute respiratory syndrome coronavirus-2 antibody testing, the results of which were all negative. Four out of 15 centres questioned perceived an increased incidence in paediatric Bell's palsy.
Clinicians are encouraged to be vigilant to the increase in paediatric Bell's palsy seen during the coronavirus disease 2019 pandemic, which may represent a post-viral sequela of coronavirus disease 2019.
Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States.
Design, setting, and participants:
Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States.
The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States.
In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56-–2.69), male sex (aOR, 2.44; 95% CI, 1.34–4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15–4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00–1.37), male sex (aOR, 2.34; 95% CI, 1.54–3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09–2.85).
In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.
Few studies have validated FFQ estimates of dietary glycaemic index (GI) and load (GL). We investigated how well our estimates of overall GI and GL from FFQs correlate with estimates from repeated 24 h recall data to validate overall GI and GL in the Adventist Health Study-2 (AHS-2).
The AHS-2 is a prospective population-based cohort of 95 873 Seventh-day Adventist adult church members enrolled from 2002 to 2007 to investigate diet, cancer and mortality.
A 204-item FFQ was used to assess race- and gender-specific validity of GI and GL and 24 h recall data, from the calibration sub-study, were used as the reference.
The 734 calibration study participants were randomly selected by church and included approximately equal numbers of blacks and whites but were otherwise similar to the whole cohort with respect to gender, age, education and vegetarian status.
The deattenuated correlation coefficients for overall GI ranged from 0·19 (95 % CI −0·06, 0·53) in black men to 0·46 (95 % CI 0·40, 0·60) in black women, with both non-black men and women falling between those values (0·45 (95 % CI 0·35, 0·65) and 0·38 (95 % CI 0·27, 0·57), respectively). GL correlations were somewhat higher for all study participants. When looking at the entire cohort, the deattenuated validity correlation value for overall GI was (r 0·38, 95 % CI 0·36, 0·47) and GL was (r 0·39, 95 % CI 0·34, 0·49).
Our findings support the cautious use of our FFQ in epidemiological studies when assessing associations of overall GI and GL with disease risk. However, observed differences by race should be considered when interpreting results.
Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.
We explain how two landmark Supreme Court cases, Motor Vehicles Manufacturers Association of the U.S. v. State Farm Mutual Automobile Insurance Co. (1983) and Chevron U.S.A., Inc., v. Natural Resources Defense Council, Inc. (1984), have constrained congressional and presidential control of the bureaucracy. We provide an overview of these cases, and we note how the dominant theories of bureaucratic policy making in the political science literature fail to account for judicial doctrine in a meaningful way. We illustrate the implications of these cases for recent debates regarding regulatory rollbacks in the Trump administration, and we argue that bureaucratic control over the past forty years has tilted in favor of the judicial branch of American national government.
Depression is characterised by negative views of the self. Antidepressant treatment may remediate negative self-schema through increasing processing of positive information about the self. Changes in affective processing during social interactions may increase expression of prosocial behaviours, improving interpersonal communications.
To examine whether acute administration of citalopram is associated with an increase in positive affective learning biases about the self and prosocial behaviour.
Healthy volunteers (n = 41) were randomised to either an acute 20 mg dose of citalopram or matched placebo in a between-subjects double-blind design. Participants completed computer-based cognitive tasks designed to measure referential affective processing, social cognition and expression of prosocial behaviours.
Participants administered citalopram made more cooperative choices than those administered placebo in a prisoner's dilemma task (β = 20%, 95% CI: 2%, 37%). Exploratory analyses indicated that participants administered citalopram showed a positive bias when learning social evaluations about a friend (β = 4.06, 95% CI: 0.88, 7.24), but not about the self or a stranger. Similarly, exploratory analyses found evidence of increased recall of positive words and reduced recall of negative words about others (β = 2.41, 95% CI: 0.89, 3.93), but not the self, in the citalopram group.
Participants administered citalopram showed greater prosocial behaviours, increased positive recall and increased positive learning of social evaluations towards others. The increase in positive affective bias and prosocial behaviours towards others may, at least partially, be a mechanism of antidepressant effect. However, we found no evidence that citalopram influenced self-referential processing.