We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
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 no-reply@cambridge.org
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.
We present the serendipitous radio-continuum discovery of a likely Galactic supernova remnant (SNR) G305.4–2.2. This object displays a remarkable circular symmetry in shape, making it one of the most circular Galactic SNRs known. Nicknamed Teleios due to its symmetry, it was detected in the new Australian Square Kilometre Array Pathfinder (ASKAP) Evolutionary Map of the Universe (EMU) radio–continuum images with an angular size of 1 320$^{\prime\prime}$$\times$1 260$^{\prime\prime}$ and PA = 0$^\circ$. While there is a hint of possible H$\alpha$ and gamma-ray emission, Teleios is exclusively seen at radio–continuum frequencies. Interestingly, Teleios is not only almost perfectly symmetric, but it also has one of the lowest surface brightnesses discovered among Galactic SNRs and a steep spectral index of $\alpha$=–0.6$\pm$0.3. Our best estimates from Hi studies and the $\Sigma$–D relation place Teleios as a type Ia SNR at a distance of either $\sim$2.2 kpc (near-side) or $\sim$7.7 kpc (far-side). This indicates two possible scenarios, either a young (under 1 000 yr) or a somewhat older SNR (over 10 000 yr). With a corresponding diameter of 14/48 pc, our evolutionary studies place Teleios at the either early or late Sedov phase, depending on the distance/diameter estimate. However, our modelling also predicts X-ray emission, which we do not see in the present generation of eROSITA images. We also explored a type Iax explosion scenario that would point to a much closer distance of $\lt$1 kpc and Teleios size of only $\sim$3.3 pc, which would be similar to the only known type Iax remnant SN1181. Unfortunately, all examined scenarios have their challenges, and no definitive Supernova (SN) origin type can be established at this stage. Remarkably, Teleios has retained its symmetrical shape as it aged even to such a diameter, suggesting expansion into a rarefied and isotropic ambient medium. The low radio surface brightness and the lack of pronounced polarisation can be explained by a high level of ambient rotation measure (RM), with the largest RM being observed at Teleios’s centre.
Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.
Methods:
A PubMed literature search covering the past 30 years was conducted using keywords such as “5-HT2A receptor,” “psychedelics,” “immune system,” and “HPA axis.” Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.
Results:
Preclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-κB, and reduced cytokine expression such as TNF-α, IL-6, and IL-1β at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.
Conclusion:
Further studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Although early health technology assessment (HTA) is increasingly being used to guide and inform decisions on product development, a consensus definition is currently lacking. A working group under the HTA International Society was established to develop a consensus-based definition of early HTA. The working group developed a definition using an iterative process that comprised five stages of work and included a two-round Delphi survey with 133 respondents in the first and 99 respondents in the second round of the survey, with various backgrounds and levels of expertise. Following this process, the working group reached the first consensus-based definition of early HTA, which is an HTA conducted to inform decisions about subsequent development, research, and/or investment by explicitly evaluating the potential value of a conceptual or actual health technology. In total, 86 (87 percent) of the 99 panelists who participated in the second round of the Delphi survey either strongly agreed or agreed with this definition. This consensus definition represents an important milestone in early HTA. It will enhance the uniformity of terminology, increasing the visibility of research and policy in this field. We also hope that it will act as a catalyst sparkling further research and developments in this discipline.
We present the Evolutionary Map of the Universe (EMU) survey conducted with the Australian Square Kilometre Array Pathfinder (ASKAP). EMU aims to deliver the touchstone radio atlas of the southern hemisphere. We introduce EMU and review its science drivers and key science goals, updated and tailored to the current ASKAP five-year survey plan. The development of the survey strategy and planned sky coverage is presented, along with the operational aspects of the survey and associated data analysis, together with a selection of diagnostics demonstrating the imaging quality and data characteristics. We give a general description of the value-added data pipeline and data products before concluding with a discussion of links to other surveys and projects and an outline of EMU’s legacy value.
Japan's searing summer of 2013 saw the lid slide further off Fukushima Daiichi and its Pandora's box of radioactive and political crises. The company in charge, Tokyo Electric Power Company (Tepco), already Japan's most distrusted firm, was irredeemably exposed as dangerously incompetent. A slew of reports concerning leaks of high-level radiation led to increasingly concerned appeals, from within Japan and from overseas, for the Abe Shinzo government to take over at Fukushima Daiichi.
Research in community ecology, anthropology, and ethnoprimatology has identified mixed-species animal groups, and we argue that Moffett's definition of society allows these groups to qualify as societies. The existence of mixed-species society has two implications – that societies are structured by social norms, and that it may be more common to belong to multiple societies than Moffett suggests.
We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.
Shiga toxin-producing Escherichia coli (STEC) is a group of bacteria that causes gastrointestinal illness and occasionally causes large foodborne outbreaks. It represents a major public health concern due to its ability to cause severe illness which can sometimes be fatal. This study was undertaken as part of a rapid investigation into a national foodborne outbreak of STEC O145. On 22 May 2024, United Kingdom (UK) public health agencies and laboratories identified an increase in stool specimens submissions and patients testing positive for Shiga toxin-producing E. coli (STEC). Whole genome sequencing (WGS) identified serotype O145:H28 stx2a/eae belonging to the same five single nucleotide polymorphism (SNP) single linkage cluster as the causative agent. By 3 July 2024, 288 cases had been linked to the cluster. Most cases were adults (87%) and females (57%), 49% were hospitalized with a further 10% attending emergency care. Descriptive epidemiology and analytical studies were conducted which identified consumption of nationally distributed pre-packed sandwiches as a common food exposure. The implicated food business operators voluntarily recalled ready-to-eat sandwiches and wraps containing lettuce on 14 June 2024.
The prenatal and early-life periods pose a crucial neurodevelopmental window whereby disruptions to the intestinal microbiota and the developing brain may have adverse impacts. As antibiotics affect the human intestinal microbiome, it follows that early-life antibiotic exposure may be associated with later-life psychiatric or neurocognitive outcomes.
Aims
To explore the association between early-life (in utero and early childhood (age 0–2 years)) antibiotic exposure and the subsequent risk of psychiatric and neurocognitive outcomes.
Method
A search was conducted using Medline, PsychINFO and Excerpta Medica databases on 20 November 2023. Risk of bias was assessed using the Newcastle-Ottawa scale, and certainty was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) certainty assessment.
Results
Thirty studies were included (n = 7 047 853 participants). Associations were observed between in utero antibiotic exposure and later development of autism spectrum disorder (ASD) (odds ratio 1.09, 95% CI: 1.02–1.16) and attention-deficit hyperactivity disorder (ADHD) (odds ratio 1.19, 95% CI: 1.11–1.27) and early-childhood exposure and later development of ASD (odds ratio 1.19, 95% CI: 1.01–1.40), ADHD (odds ratio 1.33, 95% CI: 1.20–1.48) and major depressive disorder (MDD) (odds ratio 1.29, 95% CI: 1.04–1.60). However, studies that used sibling control groups showed no significant association between early-life exposure and ASD or ADHD. No studies in MDD used sibling controls. Using the GRADE certainty assessment, all meta-analyses but one were rated very low certainty, largely owing to methodological and statistical heterogeneity.
Conclusions
While there was weak evidence for associations between antibiotic use in early-life and later neurodevelopmental outcomes, these were attenuated in sibling-controlled subgroup analyses. Thus, associations may be explained by genetic and familial confounding, and studies failing to utilise sibling-control groups must be interpreted with caution. PROSPERO ID: CRD42022304128
Social impact has been widely discussed by the engineering community, but studies show that there is currently little systematic consideration of the social impact of products in both academia and in industry beyond social impacts on health and safety. While Failure Mode and Effect Analysis (FMEA) is useful for evaluating health and safety risks, new developments are needed to create an FMEA-style evaluation that can be applied to a wide range of social impacts for engineered products. The authors describe necessary modifications to traditional FMEA that transform it into a tool for social impact analysis. The modification of FMEA involves the introduction of positive and negative impacts, the inclusion of discrete and continuous impacts, the consideration of various stakeholder types, and the inclusion of uncertainty in place of detectability. This modified FMEA is referred to in this paper as Social Impact Effects Analysis (SIEA). The paper describes how SIEA is performed and articulates the potential benefits of SIEA.
The strategies of MNEs at the start of the twenty-first century were shaped by the turbulent international environment that redefined global competition in the closing decades of the twentieth century. It was during that turmoil that a number of different perspectives and prescriptions emerged about how companies could create strategic advantages in their worldwide businesses.
Historically, the strategic challenge for a company has been viewed primarily as one of protecting potential profits from erosion through either competition or bargaining. Such erosion of profits could be caused not only by the actions of competitors but also by the bargaining powers of customers, suppliers, and governments. The key challenge facing a company was assumed to be its ability to maintain its independence by maintaining strong control over its activities. Furthermore, this strategic approach emphasized the defensive value of making other entities depend on it by capturing critical resources, building switching costs, and exploiting other vulnerabilities.
This book focuses on the management challenges associated with developing the strategies, building the organizations, and managing the operations of companies whose activities stretch across national boundaries. Operating in an international rather than a domestic arena clearly presents managers with many new opportunities. Having worldwide operations not only gives a company access to new markets and low-cost resources, it also opens up new sources of information and knowledge and broadens the options for the strategic moves the company might make to compete with its domestic and international rivals. However, with all these new opportunities come the challenges of managing strategy, organization, and operations that are innately more complex, diverse, and uncertain.