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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.
The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range $0.4\lt z\lt1.0$, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg$^2$ of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg$^2$ of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at $0.4\lt z\lt1$. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth $\tau\gt1$, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5–20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg$^2$ ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
This paper discusses the succession ceremony organized by Aḥmad ibn Ṭūlūn in 270/884 for his son and heir, Khumārawayh, as described by Egyptian Arabic sources, notably Sīrat Aḥmad ibn Ṭūlūn of al-Balawī, an underutilized text for Abbasid history. The paper considers three overlapping questions. First, how should the accounts be read, as “representational” or, alternatively, as prescriptive, thus of a piece with elements of the Mirror for Princes literature? Second, were Ṭūlūnid networks of loyalty and dependence solely reliant on material inducements or did individuals invest themselves in the Egyptian regime beyond the point of self-interest? The question goes to the problem of material vs. emotional ties of dependency. And, third, was Ibn Ṭūlūn successful in creating a lasting power base? The question goes to the extent to which his contemporaries signed on to his “project” of redefining relations with the Abbasid center.
Single-molecule techniques to analyze proteins and other biomolecules involving labels and tethers have allowed for new understanding of the underlying biophysics; however, the impact of perturbation from the labels and tethers has recently been shown to be significant in several cases. New approaches are emerging to measure single proteins through light scattering without the need for labels and ideally without tethers. Here, the approaches of interference scattering, plasmonic scattering, microcavity sensing, nanoaperture optical tweezing, and variants are described and compared. The application of these approaches to sizing, oligomerization, interactions, conformational dynamics, diffusion, and vibrational mode analysis is described. With early commercial successes, these approaches are poised to have an impact in the field of single-molecule biophysics.
Background: There is limited data regarding the benefits of direct inoculation of sterile pericardial fluid into blood culture bottles. We discovered widespread adoption of this practice at our institution during pericardiocenteses and became concerned about over-capturing of skin flora contaminants. We aimed to understand how organisms detected in pericardial fluid inoculated into blood culture bottles were interpreted clinically. Methods: We investigated a cluster of four patients with coagulase-negative Staphylococcus (CoNS) isolated in pericardial fluid inoculated blood culture bottles (PF-BCxBs) over a 2-week period; three of these patients had recent cardiac surgery and were initially flagged as potential SSIs. We further expanded to a retrospective review and identified 28 patients with ≥1 organism isolated from PF-BCxBs from 7/2021 to 6/2023. Clinical, microbiological, and pharmacy data were abstracted. The primary outcome was the proportion of patients with a clinically diagnosed infection. Results: Investigation into the initial cluster revealed a pseudo-outbreak - three of four patients had no clinical evidence of infection (CoNS was deemed a contaminant); one was treated for a potential infection. All patients had concomitant negative routine fluid cultures. Discussions with the cardiology teams revealed areas for improvement in the process for inoculating fluid into blood culture bottles. From the two-year review, 18% (5/28) of patients were clinically diagnosed with an infection (two Staphylococcus aureus; two CoNS; one Candida rugosa). Of the patients without Staphylococcus aureus, all three had a concomitant negative routine fluid culture, were receiving antibiotics prior to pericardiocentesis, and had white blood cell counts (WBC) >12 K/uL. The remaining 82% (23/28) of patients were deemed not to have an infection. Of these 23 patient without infection, organisms isolated were 16 CoNS (70%) and seven Cutibacterium species (30%). None of these patients had a fever, one (4%) was receiving pre-pericardiocentesis antibiotics, and three (9%) had WBC >12 K/uL. 70% (16/23) of these patients were started on antibiotics after gram-stain results; all were eventually discontinued (mean antibiotic days = 2, range 1-5 days). 83% (19/23) of these patients had a concomitant negative routine fluid culture. Conclusion: The majority of patients with an organism isolated from PF-BCxBs had either CoNS or Cutibacterium species and were deemed not to have a clinical infection. Within the small cohort limitations, clinical utility of blood culture bottle inoculation seems highest for patients with pre-procedural concern for infection. IPC teams should be aware of the non-pathogenic skin flora frequency and potential implication on SSI surveillance.
Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer’s disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.
Method:
Three hundred and seventy older adults (aged 75.8 +/− 5.8 years) completed a week of remote daily testing on the Ambulatory Research in Cognition (ARC) smartphone platform and also completed clinical, genetic, and conventional in-clinic cognitive assessments. RT variability was assessed in a brief (20-40 seconds) processing speed task using two different measures of variability, the Coefficient of Variation (CoV) and the Root Mean Squared Successive Difference (RMSSD) of RTs on correct trials.
Results:
Symptomatic participants showed greater variability compared to cognitively normal participants. When restricted to cognitively normal participants, APOE ε4 carriers exhibited greater variability than noncarriers. Both CoV and RMSSD showed significant, and similar, correlations with several in-clinic cognitive composites. Finally, both RT variability measures significantly mediated the relationship between APOE ε4 status and several in-clinic cognition composites.
Conclusions:
Attentional fluctuations over 20–40 seconds assessed in daily life, are sensitive to clinical status and genetic risk for AD. RT variability appears to be an important predictor of cognitive deficits during the preclinical disease stage.
Timely intervention is beneficial to the effectiveness of eating disorder (ED) treatment, but limited capacity within ED services means that these disorders are often not treated with sufficient speed. This service evaluation extends previous research into guided self-help (GSH) for adults with bulimic spectrum EDs by assessing the feasibility, acceptability, and preliminary effectiveness of virtually delivered GSH using videoconferencing.
Method:
Patients with bulimia nervosa (BN), binge eating disorder (BED) and other specified feeding and eating disorders (OSFED) waiting for treatment in a large specialist adult ED out-patient service were offered virtually delivered GSH. The programme used an evidence-based cognitive behavioural self-help book. Individuals were supported by non-expert coaches, who delivered the eight-session programme via videoconferencing.
Results:
One hundred and thirty patients were allocated to a GSH coach between 1 September 2020 and 30 September 2022; 106 (82%) started treatment and 78 (60%) completed treatment. Amongst completers, there were large reductions in ED behaviours and attitudinal symptoms, measured by the ED-15. The largest effect sizes for change between pre- and post-treatment were seen for binge eating episode frequency (d = –0.89) and concerns around eating (d = –1.72). Patients from minoritised ethnic groups were over-represented in the non-completer group.
Conclusions:
Virtually delivered GSH is feasible, acceptable and effective in reducing ED symptoms amongst those with bulimic spectrum disorders. Implementing virtually delivered GSH reduced waiting times, offering a potential solution for long waiting times for ED treatment. Further research is needed to compare GSH to other brief therapies and investigate barriers for patients from culturally diverse groups.
This study uses isotope and microbotanical data from the analysis of teeth and dental calculus to investigate camelid diet and foddering practices at Quilcapampa (AD 835–900). By providing taxonomically specific evidence of foods consumed, botanical data from dental calculus complement the more general impressions of photosynthetic pathways obtained through isotopic analysis. Results suggest that the camelid diet incorporated maize (Zea mays), algarrobo (Prosopis sp.), potato chuño (Solanum sp.), and other resources. The life-history profile of one camelid (Individual 3) reveals dietary change from mainly C3 plants to more C4 plant contributions as the animal aged. This pattern is supported by carbonate isotope results indicating that this individual spent its youth in the mid-valley ecozone before becoming more mobile later in life. As this life-history example shows, isotopic and microbotanical analyses are complementary approaches, clarifying a pattern of seasonal transhumance that linked the lives of humans and animals along the Middle Horizon (AD 600–1000) caravan networks that crisscrossed the central Andes.
The letter of the law is its literal meaning. Here, the spirit of the law is its perceived intention. We tested the hypothesis that violating the spirit of the law accounts for culpability above and beyond breaking the mere letter. We find that one can incur culpability even when the letter of the law is not technically broken. We examine this effect across various legal contexts and discuss the implications for future research directions.
Developments in third/ninth-century Egypt relate to the wider history of the Abbasid imperial realm in a number of ways. These had to do, in one sense or another, with the fraying of the Arab Islamic empire, governed, at this point, by the Abbasid house.1 This chapter considers one such development: the turn to control over Egypt by the Turkic–Central Asian military command in Samarra. My argument is that, at a moment in which the Abbasid state was struggling to sustain its hold over a once far-flung but now shrinking domain, it ceded authority over Egypt to those same military/political circles. Egypt, in this scenario, was a key interest of the Samarran commanders and in defense of which they devoted considerable energy and resources. It was a matter of consolidating authority over the province’s considerable public wealth, to be sure, but the sources point to apparent private interests – specifically, landholdings – on the part of the commanders as well.
As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.
Methods:
The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.
Results:
Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.
Conclusion:
It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
Stakeholder engagement is increasingly expected by funders and valued by researchers in clinical and translational science, yet many researchers lack access to expert consultation or training in selecting appropriate stakeholder engagement methods. We describe the development of a novel Stakeholder Engagement Navigator webtool. We conducted an environmental scan and literature review, along with investigator interviews, surveys, and engagement expert facilitated group discussion. We formally reviewed and cataloged 29 distinct engagement methods. To develop the webtool, we used an iterative design process that followed Design Thinking phases: empathize, define, ideate, prototype, and test. As prioritized during user testing, the Stakeholder Engagement Navigator webtool both educates and guides investigators in selecting an engagement method based on key criteria. The V1.0 Navigator webtool filters methods first by purpose of engagement (noted by 62% of users as the highest priority criteria), then by budget, time per stakeholder interaction, and total interactions. The tool is available at DICEMethods.org. The Stakeholder Engagement Navigator webtool is a user-centered, interactive webtool suitable for use by researchers seeking guidance on appropriate stakeholder engagement methods for clinical and translational research projects.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$11–18 arcsec, resulting in a catalogue of $\sim$220 000 sources, of which $\sim$180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Much evidence – textual, material and documentary – points to slavery in the early and medieval Islamic Middle East (c. 600-1000 CE) as a social fact, persistent and multivalent. This is especially true for the urban landscape: the presence of enslaved and freed persons would have been impossible to miss. More difficult is the reconstruction of Middle Eastern agrarian slavery. This is a survey essay with particular reference to the early Abbasid Caliphate (c. 750-950) and select questions around which debate in modern scholarship has grown. One must comb medieval Arabic texts (literary and documentary) to reconstruct patterns of early Islamic-era enslavement; the organization and dynamics of slave commerce; the demands on slave and freed labor; and the (relative) social integration of the enslaved. The Arabic/Islamic library illuminates all manner of topics, religious and secular alike. Literary references to slavery and/or enslaved persons therein are plentiful and of a great variety. One has references in works of poetry and adab, an elastic term used for a variety of Arabic prose writings. Equally numerous are references in chronicles, biographical dictionaries, and works of geography and political thought. Medieval Arabic legal and religious writings provide a considerable number of references as well.
The Inquisitions post mortem (IPMs) are a truly wonderful source for many different aspects of late medieval countryside and rural life. They have recently been made digitally accessible and interrogatable by the Mapping the Medieval Countryside project, and the first fruits of these developments are presented here. The chapters examine IPMs in connection with the landscape and topography of England, in particular markets and fairs and mills; and consider the utility of proofs of age for everyday life on such topics as the Church, retaining, and the wine trade.
Michael Hicks is Emeritus Professor of Medieval History at the University of Winchester.
Contributors: Katie A. Clarke, William S. Deller, Paul Dryburgh, Christopher Dyer, Janette Garrett, Michael Hicks, Matthew Holford, Gordon McKelvie, Stephen Mileson, Simon Payling, Matthew Tompkins, Jennifer Ward.
The inhabitants of seventh-century Arabia mobilized for warfare in a manner new to that region of the Near East: the effort fell, albeit gradually, under central authority.1 Arabia had long been a highly variegated cultural zone, encompassing the Syrian Desert, southern Mesopotamia, and the Arabian Peninsula. Acting in tandem, largely nomadic tribal forces accepted the leadership of sedentary townsmen, the great number of whom belonged to the Quraysh, an influential tribe of two towns of the Hejaz region, Mecca and Medina. If Yemen and south Arabia had long known the rule of kings, and, hence, more formal military organization, only now did the central and northern stretches of the Peninsula and southern Syria experience what can thereby be considered as early state formation. The effort was driven by an equally untested set of ethical and spiritual teachings. A charismatic figure, Muḥammad ibn ʿAbdallāh (570–632), preached a strict monotheism; these teachings served as the seedbed of what would soon be known as Islam.