To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
AI can assist the linguist in doing research on the structure of language. This Element illustrates this possibility by showing how a conversational AI based on a Large Language Model (AI LLM chatbot) can assist the Construction Grammarian, and especially the Frame Semanticist. An AI LLM chatbot is a text-generation system trained on vast amounts of text. To generate text, it must be able to find patterns in the data and mimic some linguistic capacity, at least in the eyes of a cooperative human user. The authors do not focus on whether AIs “understand” language. Rather, they investigate whether AI LLM chatbots are useful tools for linguists. They reframe the discussion from what AI LLM chatbots can do with language to what they can do for linguists. They find that a chatty LLM can labor usefully as an eliciting interlocutor, and present precise, scripted routines for prompting conversational LLMs.
Stress and depression have a reciprocal relationship, but the neural underpinnings of this reciprocity are unclear. We investigated neuroimaging phenotypes that facilitate the reciprocity between stress and depressive symptoms.
In total, 22 195 participants (52.0% females) from the population-based UK Biobank study completed two visits (initial visit: 2006–2010, age = 55.0 ± 7.5 [40–70] years; second visit: 2014–2019; age = 62.7 ± 7.5 [44–80] years). Structural equation modeling was used to examine the longitudinal relationship between self-report stressful life events (SLEs) and depressive symptoms. Cross-sectional data were used to examine the overlap between neuroimaging correlates of SLEs and depressive symptoms on the second visit among 138 multimodal imaging phenotypes.
Longitudinal data were consistent with significant bidirectional causal relationship between SLEs and depressive symptoms. In cross-sectional analyses, SLEs were significantly associated with lower bilateral nucleus accumbal volume and lower fractional anisotropy of the forceps major. Depressive symptoms were significantly associated with extensive white matter hyperintensities, thinner cortex, lower subcortical volume, and white matter microstructural deficits, mainly in corticostriatal-limbic structures. Lower bilateral nucleus accumbal volume were the only imaging phenotypes with overlapping effects of depressive symptoms and SLEs (B = −0.032 to −0.023, p = 0.006–0.034). Depressive symptoms and SLEs significantly partially mediated the effects of each other on left and right nucleus accumbens volume (proportion of effects mediated = 12.7–14.3%, p < 0.001−p = 0.008). For the left nucleus accumbens, post-hoc seed-based analysis showed lower resting-state functional connectivity with the left orbitofrontal cortex (cluster size = 83 voxels, p = 5.4 × 10−5) in participants with high v. no SLEs.
The nucleus accumbens may play a key role in the reciprocity between stress and depressive symptoms.
The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program.
We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27).
The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement.
Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.
Cross-sectional studies have shown that the COVID-19 pandemic has had a significant impact on the mental health of healthcare staff. However, it is less well understood how working over the long term in successive COVID-19 waves affects staff well-being.
To identify subpopulations within the health and social care staff workforce with differentiated trajectories of mental health symptoms during phases of the COVID-19 pandemic.
The COVID-19 Staff Wellbeing Survey assessed health and social care staff well-being within an area of the UK at four time points, separated by 3-month intervals, spanning November 2020 to August 2021.
Growth mixture models were performed on the depression, anxiety and post-traumatic stress disorder longitudinal data. Two class solutions provided the best fit for all models. The vast majority of the workforce were best represented by the low-symptom class trajectory, where by symptoms were consistently below the clinical cut-off for moderate-to-severe symptoms. A sizable minority (13–16%) were categorised as being in the high-symptom class, a group who had symptom levels in the moderate-to-severe range throughout the peaks and troughs of the pandemic. In the depression, anxiety and post-traumatic stress disorder models, the high-symptom class perceived communication from their organisation to be less effective than the low-symptom class.
This research identified a group of health service staff who reported persistently high mental health symptoms during the pandemic. This group of staff may well have particular needs in terms of the provision of well-being support services.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Screening for asymptomatic health conditions is perceived as mostly beneficial, with possible harms receiving little attention.
To quantify proximal and longer-term consequences for individuals receiving a diagnostic label following screening for an asymptomatic, non-cancer health condition.
Five electronic databases were searched (inception to November 2022) for studies that recruited asymptomatic screened individuals who received or did not receive a diagnostic label. Eligible studies reported psychological, psychosocial and/or behavioural outcomes before and after screening results. Independent reviewers screened titles and abstracts, extracted data from included studies, and assessed risk of bias (Risk of Bias in Non-Randomised Studies of Interventions). Results were meta-analysed or descriptively reported.
Sixteen studies were included. Twelve studies addressed psychological outcomes, four studies examined behavioural outcomes and none reported psychosocial outcomes. Risk of bias was judged as low (n = 8), moderate (n = 5) or serious (n = 3). Immediately after receiving results, anxiety was significantly higher for individuals receiving versus not receiving a diagnostic label (mean difference −7.28, 95% CI −12.85 to −1.71). On average, anxiety increased from the non-clinical to clinical range, but returned to the non-clinical range in the longer term. No significant immediate or longer-term differences were found for depression or general mental health. Absenteeism did not significantly differ from the year before to the year after screening.
The impacts of screening asymptomatic, non-cancer health conditions are not universally positive. Limited research exists regarding longer-term impacts. Well-designed, high-quality studies further investigating these impacts are required to assist development of protocols that minimise psychological distress following diagnosis.
Treatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.
AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.
To evaluate the effect of AXS-05 in improving anhedonic symptoms in MDD.
GEMINI (N=327) was a randomized, double-blind, placebo-controlled, 6-week study, which randomized adults with MDD to AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) or placebo, twice daily. The primary endpoint was change from baseline in the MADRS total score at Week 6. A post-hoc analysis was conducted to determine the impact of AXS-05 versus placebo on the 5-item MADRS anhedonia subscale (MAS).
Baseline MAS scores were 19.8 and 19.6 in the AXS-05 and placebo group, respectively. At Week 1, AXS-05 treatment resulted in a significant mean reduction from baseline in the MAS score of 4.44 versus 2.69 points for placebo (p< 0.001). At Week 6, the mean reduction from baseline in the MAS was 9.70 for AXS-05 compared to 7.22 for placebo (p=0.001). Response rates (≥ 50% MAS improvement) were significantly greater for AXS-05 compared to placebo at Week 1 (p< 0.001) and at every time point thereafter.
Treatment with AXS-05 was generally safe and well tolerated. The most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.
Treatment with AXS-05 rapidly and significantly reduced anhedonic symptoms as well as overall depressive symptoms.
An emergent volume electron microscopy technique called cryogenic serial plasma focused ion beam milling scanning electron microscopy (pFIB/SEM) can decipher complex biological structures by building a three-dimensional picture of biological samples at mesoscale resolution. This is achieved by collecting consecutive SEM images after successive rounds of FIB milling that expose a new surface after each milling step. Due to instrumental limitations, some image processing is necessary before 3D visualization and analysis of the data is possible. SEM images are affected by noise, drift, and charging effects, that can make precise 3D reconstruction of biological features difficult. This article presents Okapi-EM, an open-source napari plugin developed to process and analyze cryogenic serial pFIB/SEM images. Okapi-EM enables automated image registration of slices, evaluation of image quality metrics specific to pFIB-SEM imaging, and mitigation of charging artifacts. Implementation of Okapi-EM within the napari framework ensures that the tools are both user- and developer-friendly, through provision of a graphical user interface and access to Python programming.
Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.
Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).
Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.
Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
In October 2010, the provincial government of Ontario, Canada enacted the Open for Business Act (OBA). A central component of the OBA is its provisions aiming to streamline the enforcement of Ontario’s Employment Standards Act (ESA). The OBA’s changes to the ESA are an attempt to manage a crisis of employment standards (ES) enforcement, arising from decades of ineffective regulation, by entrenching an individualised enforcement model. The Act aims to streamline enforcement by screening people assumed to be lacking definitive proof of violations out of the complaints process. The OBA therefore produces a new category of ‘illegitimate claimants’ and attributes administrative backlogs to these people. Instead of improving the protection of workers, the OBA embeds new racialised and gendered modes of exclusion in the ES enforcement process.
Following the 2008 financial crisis, austerity measures have been introduced in many national contexts to reorganise public sector work and redesign labour laws and labour policies. At the same time, right-populist discourses and movements have arisen in ways that give both legitimacy and voice to the politics of austerity. Toronto, Canada, provides a world-renowned case of populist experimentation at the metropolitan scale, as the actions of Mayor Rob Ford typified this nexus of austerity and populism. Set in the context of Ford’s term as Mayor of Toronto (2010–2014), this article asks how the combined rise of austerity and right populism creates both new challenges and new opportunities for public sector labour in urban spaces. We argue that public sector unions are central in both the making and unmaking of populist austerity and identify potential trajectories for organised labour in the face of the continuation of austerity-driven politics.
The dominant paradigm of experiments in the social and behavioral sciences views an experiment as a test of a theory, where the theory is assumed to generalize beyond the experiment's specific conditions. According to this view, which Alan Newell once characterized as “playing twenty questions with nature,” theory is advanced one experiment at a time, and the integration of disparate findings is assumed to happen via the scientific publishing process. In this article, we argue that the process of integration is at best inefficient, and at worst it does not, in fact, occur. We further show that the challenge of integration cannot be adequately addressed by recently proposed reforms that focus on the reliability and replicability of individual findings, nor simply by conducting more or larger experiments. Rather, the problem arises from the imprecise nature of social and behavioral theories and, consequently, a lack of commensurability across experiments conducted under different conditions. Therefore, researchers must fundamentally rethink how they design experiments and how the experiments relate to theory. We specifically describe an alternative framework, integrative experiment design, which intrinsically promotes commensurability and continuous integration of knowledge. In this paradigm, researchers explicitly map the design space of possible experiments associated with a given research question, embracing many potentially relevant theories rather than focusing on just one. The researchers then iteratively generate theories and test them with experiments explicitly sampled from the design space, allowing results to be integrated across experiments. Given recent methodological and technological developments, we conclude that this approach is feasible and would generate more-reliable, more-cumulative empirical and theoretical knowledge than the current paradigm—and with far greater efficiency.
Innovative shoe insoles, designed to enhance sensory information on the plantar surface of the feet, could help to improve walking in people with Multiple Sclerosis.
To compare the effects of wearing textured versus smooth insoles, on measures of gait, foot sensation and patient-reported outcomes, in people with Multiple Sclerosis.
A prospective, randomised controlled trial was conducted with concealed allocation, assessor blinding and intention-to-treat analysis. Thirty ambulant men and women with multiple sclerosis (MS) (Disease Steps rating 1–4) were randomly allocated to wear textured or smooth insoles for 12 weeks. Self-reported insole wear and falls diaries were completed over the intervention period. Laboratory assessments of spatiotemporal gait patterns, foot sensation and proprioception, and patient-reported outcomes, were performed at Weeks 0 (Baseline 1), 4 (Baseline 2) and 16 (Post-Intervention). The primary outcome was the size of the mediolateral base of support (stride/step width) when walking over even and uneven surfaces. Independent t-tests were performed on change from baseline (average of baseline measures) to post-intervention.
There were no differences in stride width between groups, when walking over the even or uneven surfaces (P ≥ 0.20) at post-intervention. There were no between-group differences for any secondary outcomes including gait (all P values > 0.23), foot sensory function (all P values ≥ 0.08) and patient-reported outcomes (all P values ≥ 0.23).
In our small trial, prolonged wear of textured insoles did not appear to alter walking or foot sensation in people with MS who have limited foot sensory loss. Further investigation is needed to explore optimal insole design.
Clinical Trial Registration:
Australian and New Zealand Clinical Trials Registry (ACTRN12615000421538).
Regional and local studies suggest that the Tufted Puffin Fratercula cirrhata in North America is declining in portions of its range. However, whether the overall population is declining, or its range is contracting with little change to the overall population size, is unknown. To examine population trends throughout its North American range, we assembled 11 datasets that spanned 115 years (1905–2019) and included at-sea density and encounter estimates and at-colony burrow and bird counts. We assessed trends for the California Current, Gulf of Alaska, and Bering Sea/Aleutian Islands large marine ecosystems (LME). We found: (1) nearly uniform and long-term declines of Puffins breeding in the California Current ecosystem, with most ecosystem colonies surveyed, (2) declining trends at two large colonies and in one at-sea dataset in the Gulf of Alaska LME, with the fourth smaller colony exhibiting no significant trend, and (3) positive trends at four out of five colonies in the Bering Sea/Aleutian Islands ecosystem complex, with no detectable trend at the fifth very large colony. The general pattern of Tufted Puffin declines across the California Current and Gulf of Alaska LMEs may be attributable to a variety of factors, but additional study is needed to evaluate the relative influence of potential population drivers both independently and synergistically. Potential mechanisms driving population increases in the Bering Sea/Aleutian Islands ecosystem include reduced depredation and bycatch, intrinsic population growth, and immigration. We found strong evidence for declines in two of the three LMEs evaluated representing approximately three quarters of the species’ North American range. This region of decline includes the Gulf of Alaska LME, which contains a significant portion of the species’ estimated total North American population. Despite data limitations, our analysis coupled with more focused and local studies indicates that the Tufted Puffin is a species of conservation concern.
This paper demonstrates experimentally that imposed periodic forcing can significantly alter the global flow characteristics of the flow over a double backward-facing step. The geometry consists of two equal height steps spaced up to eight step heights apart. A periodic zero-mass flux jet located at the first step's top corner was issued at frequencies ranging from below the step-mode instability frequency up to approximately five times the shear-layer instability frequency. Reattachment of the flow onto the first step was achieved for step separations as low as three single-step heights with imposed forcing; significantly shorter than the five single-step heights that occurred without forcing. A significant reduction in mean base pressure on the first step, and increase on the second step, occurred for low forcing frequencies. Even for large step separations, the effect of forcing on the flow persisted sufficiently far downstream to appreciably influence the development of the second recirculation zone. Importantly, previous forced single and unforced double backward-facing step flows provide reference cases to examine and discuss similarities and differences. This study offers insight into possibilities and potential outcomes of flow control for applications ranging from the drag reduction of ground vehicles such as pickup trucks, to enhanced mixing in industrial processes.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
This study compared the per capita annual global incidence rate of disasters caused by natural hazards with the annual world real gross domestic product, GDP (per global capita), as reported during 1961 through 2020.
Sixty (60) values for the world real GDP per global capita (in constant 2015 $USD) were compared to corresponding annual values for global incidence rates for five natural disaster subgroups and then for a total of twelve individual disaster types that comprise the subgroups; each expressed as an annual global incidence rate (in terms of annual incidence per 100,000 persons). Calculations of multiple linear regression, ANOVA, and Pearson’s correlation coefficient were performed for comparing population-adjusted values for GDP to corresponding values.
Four out of five hydrological and meteorological disasters were found to have a positive correlation with GDP. Results of the analysis revealed a relatively high degree of correlation between world GDP and the annual incidence of flood and storm disasters (P = 6.21 × 10−10 and P = 4.23 × 10−4, respectively). The annual incidence of heat waves and cold weather disasters also appeared to correlate with GDP (P = .002 and P = .019, respectively). In comparison, wet landslides indicated no such correlation (P = .862). No significant associations were found among the seven other individual biological, climatological, and geophysical disasters and GDP.
The global incidence of four extreme weather (hydrometeorological) disasters appear to be positively associated with world real GDP during 1961-2020. These findings contradict previous postulates that the risk of disaster incidence is inversely associated with the capacity of the population.
To determine base rates of invalid performance on the Test of Memory Malingering (TOMM) in patients with traumatic brain injury (TBI) undertaking rehabilitation who were referred for clinical assessment, and the factors contributing to TOMM failure.
Retrospective file review of consecutive TBI referrals for neuropsychological assessment over seven years. TOMM failure was conventionally defined as performance <45/50 on Trial 2 or Retention Trial. Demographic, injury, financial compensation, occupational, and medical variables were collected.
Four hundred and ninety one TBI cases (Median age = 40 years [IQR = 26–52], 79% male, 82% severe TBI) were identified. Overall, 48 cases (9.78%) failed the TOMM. Logistic regression analyses revealed that use of an interpreter during the assessment (adjusted odds ratio [aOR] = 8.25, 95%CI = 3.96–17.18), outpatient setting (aOR = 4.80, 95%CI = 1.87–12.31) and post-injury psychological distress (aOR = 2.77, 95%CI = 1.35–5.70) were significant multivariate predictors of TOMM failure. The TOMM failure rate for interpreter cases was 49% (21/43) in the outpatient setting vs. 7% (2/30) in the inpatient setting. By comparison, 9% (21/230) of non-interpreter outpatient cases failed the TOMM vs. 2% (4/188) of inpatient cases.
TOMM failure very rarely occurs in clinical assessment of TBI patients in the inpatient rehabilitation setting. It is more common in the outpatient setting, particularly in non-English-speaking people requiring an interpreter. The findings reinforce the importance of routinely administering stand-alone performance validity tests in assessments of clinical TBI populations, particularly in outpatient settings, to ensure that neuropsychological test results can be interpreted with a high degree of confidence.
Little is known about the early history of the chicken (Gallus gallus domesticus), including the timing and circumstances of its introduction into new cultural environments. To evaluate its spatio-temporal spread across Eurasia and north-west Africa, the authors radiocarbon dated 23 chicken bones from presumed early contexts. Three-quarters returned dates later than those suggested by stratigraphy, indicating the importance of direct dating. The results indicate that chickens did not arrive in Europe until the first millennium BC. Moreover, a consistent time-lag between the introduction of chickens and their consumption by humans suggests that these animals were initially regarded as exotica and only several centuries later recognised as a source of ‘food’.