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The growing utility and availability of genome-scale sequencing has led to increasingly broad incorporation across specialty disciplines of clinical research. However, classification of clinical relevance of genetic variation is an inherently clinical task, and the expertise to perform the necessary analysis, confirmation and reporting of these variants is not available in all research teams; consequently, disclosure of genomic variants to research participants remains challenging for many researchers. Advancing genomic medicine as a standard of care first requires institutional commitment and partnerships in supporting genomics in varied research studies that are inclusive of return of results to participants.
Materials and methods:
The University of North Carolina at Chapel Hill has vast experience with genetics in both clinical and research realms. By utilizing historical experience and input from key players, the Clinical GENomic analYSIS (GENYSIS) core facility was created as a case study and aims to provide a roadmap for research organizations to implement their own genomic sequencing core facilities.
Results:
The core has established a molecular sign-out conference, partnered with other core facilities on campus, and provides five main services: bioinformatics, variant analysis, clinical reporting, post-test services, and consultation with project advising. This paper presents case examples with discussion of continuous methodology improvements and embedded educational activities.
Conclusion:
This novel shared research resource enables clinical researchers with limited staff and genomics expertise to provide clinically relevant results to their study participants, expanding the reach of genomics research.
Polarimetric multi-offset radio-echo sounding offers improved constraints on englacial thermal conditions, basal properties and ice crystal orientation compared to standard monostatic observations. Nevertheless, such surveys are uncommon in glaciology and are typically limited in offset due to cable losses. In the 2023–24 austral summer, we deployed two radar systems on Eastwind Glacier and the McMurdo Ice Shelf in Antarctica, collecting five polarimetric common-midpoint (CMP) surveys. Using an Autonomous phase-sensitive Radio-Echo Sounder (ApRES), modified with off-the-shelf radio frequency-over-fiber (RFoF) hardware and a low-loss fiber optic link, we detect bed reflections at offsets up to the equivalent of four ice thicknesses, well beyond the theoretical point of total internal reflection. A second, cable-less system built around a software-defined radio (SDR) was deployed simultaneously as an unsynchronized receiver recording the same ApRES transmitter. These co-located datasets demonstrate the potential for cabled radar systems with integrated RFoF technology for extending maximum offsets by overcoming attenuation losses inherent to coaxial cables. Furthermore, we perform polarimetric amplitude-vs-offset analysis to probe glacier dielectric structure. Finally, we present data from deployment of the fiber optic system on Thwaites Glacier, where we detect bed reflections at an offset of 4 km, demonstrating operation on thick ice (~2.2 km).
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 walia ibex Capra walie is endemic to the Simien Mountains, Ethiopia, and is a national symbol. The Simien Mountains National Park was established in 1966 to protect the last 200 walia ibexes from extinction. We coordinated a population census across their c. 100 km2 range in 2015 and annually during 2019–2024. We counted 865 walia ibexes of all age and sex classes in 2015; this dropped to 650 in 2019–2021, reducing further to 306 in 2024. We investigated this decline through interviews with representatives from neighbouring communities including park personnel, village elders, farmers, local authority staff and militia. More than 70% of those interviewed attributed the drop in walia ibex numbers to poaching, both for food and medicinal purposes. Instability as a result of the Covid-19 crisis and the 2021–2022 war was seen as the fundamental cause. A species action plan is in preparation to mobilize local community ambassadors and increase protection. A database of individually recognized walia ibexes would increase our understanding of population dynamics and distribution to complement the annual counts. We recommend a change of the species’ IUCN Red List status from Vulnerable to Critically Endangered based on the recent, severe population decline and limited extent of occurrence. This status update would accurately reflect the high extinction risk of the walia and help to mobilize resources for urgent conservation actions.
Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.
Aims
To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.
Method
We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.
Results
Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.
Conclusions
We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.
In the three years since the law on adult deceased organ donation consent in England changed to include an opt-out system, there has been no discernible change to donation rates. The lack of a positive impact on donation rates was predicted by many of those who took part in debates before and during the passage of the Bill through Parliament. This invites the question as to why England moved to an opt-out system for organ donation despite equivocal evidence of likely benefit and opposition from expert health professional organisations. To address this question qualitative analyses of Parliamentary debates on organ donation was undertaken. This revealed a shift from a dominant position, which gave primacy to the evidence of likely effects, towards a more normative position where a deemed consent option was viewed as the ‘correct thing to do’ and the limited and conflicting evidence viewed in a positive light. By 2017, following Wales's move to an opt-out system, together with continued lobbying for similar changes for England by professional and patient groups, alongside sustained public popularity for organ donation, the balance of opinion had shifted towards a system where deemed consent would become the default position for most English adults
The feature [+spread glottis] ([+s.g.]) denotes that a speech sound is produced with a wide glottal aperture with audible voiceless airflow. Icelandic is unusual in the degree to which [+spread glottis] is involved in the phonology: in /h/, pre-aspirated and post-aspirated stops, voiceless fricatives and voiceless sonorants. The ubiquitousness of the feature could potentially affect the rate and process of its acquisition. This paper investigates the development of [+s.g.] in Icelandic, both in general and in a range of contexts, in a cross-sectional study of 433 typically developing Icelandic-speaking children aged two to seven years. As a feature, [+s.g.] is acquired early in Icelandic, although specific sound classes lag behind due to other output constraints. Children reach mastery of [+s.g.] by age three except in word-initial post-aspirated stops and voiceless nasals. Findings are interpreted in light of the literature on the feature and its development.
Depictions of mythical beings appear in many different forms of art world-wide, including rock art of various ages. In this paper we explore a particular type of imagery, back-to-back figures, consisting of two human-like figures or animals of the same species next to each other and facing in opposite directions. Some human-like doubles were joined at the back rather than side-by-side, but also face opposite directions. In this paper, we report on new research on rock art, bark paintings and recent paintings on paper and chart a 9000-year history of making aesthetically, symbolically and spiritually powerful back-to-back figures in Arnhem Land, Northern Territory, Australia.
Cassowaries (Casuarius) are one of the largest indigenous animal species of New Guinea. Researchers have long been trying to understand their local socio-cultural significance. Here we present new results from interviews recorded in 2018 on ethnography associated with bone daggers, a material culture ornament and tool carved from the cassowary's tibiotarsus. We present a ‘storied notion’—a contemporary narrative from oral history of why cassowary is not simply a bird, and briefly describe cassowary bone ornamentation in Auwim, East Sepik Province of Papua New Guinea. By exploring the material history of Casuarius through a ‘storied notion’ approach, we reveal that cassowary bone daggers in rock art are narrative ideas of the species from its landscape to ornamentation and through to people's cosmological beliefs surrounding Casuarius. We argue that the cassowary bone dagger stencil can be seen as part of the life history of this animal.
A projection by the superior colliculus to the supraoculomotor area (SOA) located dorsal to the oculomotor complex was first described in 1978. This projection’s targets have yet to be identified, although the initial study suggested that vertical gaze motoneuron dendrites might receive this input. Defining the tectal targets is complicated by the fact the SOA contains a number of different cell populations. In the present study, we used anterograde tracers to characterize collicular axonal arbors and retrograde tracers to label prospective SOA target populations in macaque monkeys. Close associations were not found with either superior or medial rectus motoneurons whose axons supply singly innervated muscle fibers. S-group motoneurons, which supply superior rectus multiply innervated muscle fibers, appeared to receive a very minor input, but C-group motoneurons, which supply medial rectus multiply innervated muscle fibers, received no input. A number of labeled boutons were observed in close association with SOA neurons projecting to the spinal cord, or the reticular formation in the pons and medulla. These descending output neurons are presumed to be peptidergic cells within the centrally projecting Edinger–Westphal population. It is possible the collicular input provides a signaling function for neurons in this population that serve roles in either stress responses, or in eating and drinking behavior. Finally, a number of close associations were observed between tectal terminals and levator palpebrae superioris motoneurons, suggesting the possibility that the superior colliculus provides a modest direct input for raising the eyelids during upward saccades.
The introduction of new animals into hunter-gatherer societies produces a variety of cultural responses. This article explores the role of rock art in western Arnhem Land, Australia, in helping to mediate contact-period changes in Indigenous society in the nineteenth century. The authors explore etic and emic perspectives on the ‘re-emergence’ of water buffalo into Aboriginal cultural life. Merging archaeological analysis, rock art and ethnographic accounts, the article demonstrates how such artworks were used as a tool for maintaining order in times of dramatic social change. The results of this research have significant implications for understanding how cultural groups and individuals worldwide used rock art during periods of upheaval.
Since most gaze shifts are to targets that lie at a different distance from the viewer than the current target, gaze changes commonly require a change in the angle between the eyes. As part of this response, lens curvature must also be adjusted with respect to target distance by the ciliary muscle. It has been suggested that projections by the cerebellar fastigial and posterior interposed nuclei to the supraoculomotor area (SOA), which lies immediately dorsal to the oculomotor nucleus and contains near response neurons, support this behavior. However, the SOA also contains motoneurons that supply multiply innervated muscle fibers (MIFs) and the dendrites of levator palpebrae superioris motoneurons. To better determine the targets of the fastigial nucleus in the SOA, we placed an anterograde tracer into this cerebellar nucleus in Macaca fascicularis monkeys and a retrograde tracer into their contralateral medial rectus, superior rectus, and levator palpebrae muscles. We only observed close associations between anterogradely labeled boutons and the dendrites of medial rectus MIF and levator palpebrae motoneurons. However, relatively few of these associations were present, suggesting these are not the main cerebellar targets. In contrast, labeled boutons in SOA, and in the adjacent central mesencephalic reticular formation (cMRF), densely innervated a subpopulation of neurons. Based on their location, these cells may represent premotor near response neurons that supply medial rectus and preganglionic Edinger–Westphal motoneurons. We also identified lens accommodation-related cerebellar afferent neurons via retrograde trans-synaptic transport of the N2c rabies virus from the ciliary muscle. They were found bilaterally in the fastigial and posterior interposed nuclei, in a distribution which mirrored that of neurons retrogradely labeled from the SOA and cMRF. Our results suggest these cerebellar neurons coordinate elements of the near response during symmetric vergence and disjunctive saccades by targeting cMRF and SOA premotor neurons.
Methods that include the time-varying nature of healthcare-associated infections (HAIs) avoid biases when estimating increased risk of death and excess length of stay. We determined the excess mortality risk and length of stay associated with HAIs among inpatients in Singapore using a multistate model that accommodates the timing of key events.
Design:
Analysis of existing prospective cohort study data.
Setting:
Seven public acute-care hospitals in Singapore.
Patients:
Inpatients reviewed in a HAI point-prevalence survey (PPS) conducted between June 2015 and February 2016.
Methods:
We modeled each patient’s admission over time using 4 states: susceptible with no HAI, infected, died, and discharged alive. We estimated the excess mortality risk and length of stay associated with HAIs, with adjustment for the baseline characteristics between the groups for mortality risk.
Results:
We included 4,428 patients, of whom 469 had ≥1 HAI. Using a multistate model, the expected excess length of stay due to any HAI was 1.68 days (95% confidence interval [CI], 1.15–2.21 days). Surgical site infections were associated with the longest excess length of stay of 4.68 days (95% CI, 2.60–6.76 days). After adjusting for baseline differences, HAIs were associated with increased hazards of in-hospital mortality (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.09–1.65) and decreased hazards in being discharged (aHR, 0.75; 95% CI, 0.67–0.84).
Conclusions:
HAIs are associated with increased length of hospital stay and mortality in hospitalized patients. Avoiding nosocomial infections can improve patient outcomes and free valuable bed days.
This paper explores the complex story of a particular style of rock art in western Arnhem Land known as ‘Painted Hands’. Using new evidence from recent fieldwork, we present a definition for their style, distribution and place in the stylistic chronologies of this region. We argue these motifs played an important cultural role in Aboriginal society during the period of European settlement in the region. We explore the complex messages embedded in the design features of the Painted Hands, arguing that they are more than simply hand stencils or markers of individuality. We suggest that these figures represent stylized and intensely encoded motifs with the power to communicate a high level of personal, clan and ceremonial identity at a time when all aspects of Aboriginal cultural identity were under threat.
While Vietnam is often proclaimed to be at a “crossroads”, in retrospect the period between 2014 and 2016 was genuinely an inflection point. Given heightened anxiety over Chinese assertiveness in the South China Sea and a desire to join the Transpacific Partnership (TPP), Vietnam signalled a greater desire to side with the United States than ever before. This led to a flurry of high-profile visits of Vietnamese leaders to the United States as well as an unprecedented agreement to allow independent trade unions in exchange for TPP membership. It also led to a reduction in political repression.
With President Donald Trump's decision in 2017 to pull out of the TPP, the dynamics have changed. Nearly three years after that decision, Vietnam has returned to its previous political and foreign policy orientations. As this chapter will discuss, the top contenders for power have returned to the previous hedging strategy of maintaining friendly ties with the United States while avoiding antagonizing China. The most likely successors to General Secretary Nguyen Phu Trong have maintained a generally balanced approach to political reforms and alignment with the United States. In short, it does not appear that there will be an elite-led liberalization on the horizon. If there is a question about significant elite-led political reforms in Vietnam, it is whether it is going to further centralize power in the hands of the party. On this question, we also believe that Vietnam is likely to revert to its previous collective-leadership pattern.
Although party-led political reform is largely off the table, this does not mean social pressures that could possibly force change from the outside have remained static. A number of important developments continue to challenge the regime. On the South China Sea, Vietnam's relationship with China continues to represent a volatile mobilizing issue for collective action. The environment also remains a potent social concern. Additionally, social media continues to inject a new dynamic into these issues, providing both the opportunity for citizens to challenge the regime but at the same time allowing the regime to respond more quickly and shift blame to local governments.
Rapid identification of esophageal intubations is critical to avoid patient morbidity and mortality. Continuous waveform capnography remains the gold standard for endotracheal tube (ETT) confirmation, but it has limitations. Point-of-care ultrasound (POCUS) may be a useful alternative for confirming ETT placement. The objective of this study was to determine the accuracy of paramedic-performed POCUS identification of esophageal intubations with and without ETT manipulation.
Methods
A prospective, observational study using a cadaver model was conducted. Local paramedics were recruited as subjects and each completed a survey of their demographics, employment history, intubation experience, and prior POCUS training. Subjects participated in a didactic session in which they learned POCUS identification of ETT location. During each study session, investigators randomly placed an ETT in either the trachea or esophagus of four cadavers, confirmed with direct laryngoscopy. Subjects then attempted to determine position using POCUS both without and with manipulation of the ETT. Manipulation of the tube was performed by twisting the tube. Descriptive statistics and logistic regression were used to assess the results and the effects of previous paramedic experience.
Results
During 12 study sessions, from March 2014 through December 2015, 57 subjects participated, evaluating a total of 228 intubations: 113 tracheal and 115 esophageal. Subjects were 84.0% male, mean age of 39 years (range: 22 - 62 years), with median experience of seven years (range: 0.6 - 39 years). Paramedics correctly identified ETT location in 158 (69.3%) cases without and 194 (85.1%) with ETT manipulation. The sensitivity and specificity of identifying esophageal location without ETT manipulation increased from 52.2% (95% confidence interval [CI], 43.0-61.0) and 86.7% (95% CI, 81.0-93.0) to 87.0% (95% CI, 81.0-93.0) and 83.2% (95% CI, 0.76-0.90) after manipulation (P<.0001), without affecting specificity (P=.45). Subjects correctly identified 41 previously incorrectly identified esophageal intubations. Paramedic experience, previous intubations, and POCUS experience did not correlate with ability to identify tube location.
Conclusion:
Paramedics can accurately identify esophageal intubations with POCUS, and manipulation improves identification. Further studies of paramedic use of dynamic POCUS to identify inadvertent esophageal intubations are needed.
LemaPC, O’BrienM, WilsonJ, St. JamesE, LindstromH, DeAngelisJ, CaldwellJ, MayP, ClemencyB.Avoid the Goose! Paramedic Identification of Esophageal Intubation by Ultrasound. Prehosp Disaster Med.2018;33(4):406–410
This paper addresses the motivations for producing the rare object stencils found in the rock art of western Arnhem Land. We present evidence for 84 stencils recorded as part of the Mirarr Gunwarddebim project in western Arnhem Land, northern Australia. Ranging from boomerangs to dilly bags, armlets and spearthrowers, this assemblage suggests something other than a common or ongoing culture practice of stencilling objects used in everyday life. Instead, we suggest that these stencils represent an entirely different function in rock art through a process of memorialization that was rare, opportunistic and highly selective.