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Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Rift propagation, rather than basal melt, drives the destabilization and disintegration of the Thwaites Eastern Ice Shelf. Since 2016, rifts have episodically advanced throughout the central ice-shelf area, with rapid propagation events occurring during austral spring. The ice shelf's speed has increased by ~70% during this period, transitioning from a rate of 1.65 m d−1 in 2019 to 2.85 m d−1 by early 2023 in the central area. The increase in longitudinal strain rates near the grounding zone has led to full-thickness rifts and melange-filled gaps since 2020. A recent sea-ice break out has accelerated retreat at the western calving front, effectively separating the ice shelf from what remained of its northwestern pinning point. Meanwhile, a distributed set of phase-sensitive radar measurements indicates that the basal melting rate is generally small, likely due to a widespread robust ocean stratification beneath the ice–ocean interface that suppresses basal melt despite the presence of substantial oceanic heat at depth. These observations in combination with damage modeling show that, while ocean forcing is responsible for triggering the current West Antarctic ice retreat, the Thwaites Eastern Ice Shelf is experiencing dynamic feedbacks over decadal timescales that are driving ice-shelf disintegration, now independent of basal melt.
Transitioning from mental health inpatient care to community care is often a vulnerable time in the treatment process where additional risks and anxiety may arise.
Objectives
The objective of this paper was to evaluate the progression of mental health symptoms in patients six weeks after their discharge from the hospital as the first phase of an ongoing innovative supportive program. In this study, factors that may contribute to the presence or absence of anxiety and depression symptoms, and the quality of life following a return to the community were examined. The results of this study provide evidence and baseline data for future phases of the project.
Methods
An observational design was used in this study. We collected sociodemographic and clinical data using REDCap at discharge and six weeks later. Anxiety, depression, and well-being symptoms were assessed using the Generalized Anxiety Disorder (GAD-7) questionnaire, the Patient Health Questionnaire-9 (PHQ-9), and the World Health Organization-Five Well-Being Index (WHO-5) respectively. Descriptive, Chi-square, independent T-test, and multivariate regression analyses were conducted.
Results
The survey was completed by 88 participants out of 144 (61.1% response rate). A statistically non-significant reduction in anxiety and depression symptoms was found six weeks after returning to the community based on the Chi-squared/Fisher exact test and independent t-test. As well, the mean anxiety and depression scores showed a non-significant marginal reduction after discharge compared to baseline. In the period following discharge, a non-significant increase in participants experiencing low well-being symptoms was observed, as well as a decline in the mean well-being scores. Based on logistic regression models, only baseline symptoms were significant predictors of symptoms six weeks after inpatient discharge.
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Conclusions
In the short term following hospital discharge, no significant changes were observed in mental health conditions. A collaboration between researchers and policymakers is essential for the implementation and maintenance of effective interventions to support and maintain the mental health of patients following discharge.
The transition from hospital to community settings for most mental health service users is often hindered by challenges that affect community adjustment and continuity of care. The first few weeks and days after discharge from mental health inpatient units represent a critical phase for many service users.
Objectives
This paper aims to evaluate the changes in quality of Life status, resilience, and personal recovery of individuals with mental health challenges recently discharged from acute mental health care into the community.
Methods
Data for this study were collected as part of a pragmatic stepped-wedge cluster-randomized, longitudinal approach in Alberta. A paired sample t-test and Chi-squared/Fisher test were deployed to assess changes from baseline to six weeks in the recovery assessment scale (RAS), brief resilience scale (BRS), and EuroQol-5d (EQ-5D), using an online questionnaire.
Results
A total of 306 service users were recruited, and 88 completed both baseline and six weeks, giving a response rate of 28.8%. There was no statistically significant change in the level of resilience, recovery and quality of life as measured with the brief resilience scale, recovery assessment scale and EQ-5D from baseline to six weeks (p > 0.05).
Conclusions
The study showed that there was neither an improvement nor deterioration in resilience, recovery, or quality of life status of service users six weeks post-discharge from inpatient mental health care. The lack of further progress calls into question whether the support available in the community when patients leave inpatient care is adequate to promote full recovery.
Edited by
William J. Brady, University of Virginia,Mark R. Sochor, University of Virginia,Paul E. Pepe, Metropolitan EMS Medical Directors Global Alliance, Florida,John C. Maino II, Michigan International Speedway, Brooklyn,K. Sophia Dyer, Boston University Chobanian and Avedisian School of Medicine, Massachusetts
For large entertainment tours composed of 100 to 200 personnel moving from one city (or country) to another every few days over several months’ time, the odds of numerous untoward health events occurring, some very serious, become reasonably high. Beyond rigorous schedules and living/dining in close quarters, understandable reticence to abandon one’s post can occasionally delay timely care. Accordingly, having veteran medical specialists as part of the touring team has been found to be invaluable, not only for pre-emptive minor interventions and continuity of care, but also for immediate, expert handling of serious emergencies. Experienced, well-connected touring medical specialists also provide prospective contingency plans for each destination city and venue. These medical advance plans detail the most-knowledgeable local physicians or facilities for best managing any respective medical condition. They also identify the local “point-persons” to contact for coordination of true emergencies and especially if there is a need for multi-casualty incident management at the venue. They anticipate health risks such as air quality, altitude sickness, endemic disease vectors and other concerning threats at each destination. They also train touring staff in basic life support, bleeding control and emergency equipment readiness. Touring specialists should also be well-integrated into security team functions.
Edited by
William J. Brady, University of Virginia,Mark R. Sochor, University of Virginia,Paul E. Pepe, Metropolitan EMS Medical Directors Global Alliance, Florida,John C. Maino II, Michigan International Speedway, Brooklyn,K. Sophia Dyer, Boston University Chobanian and Avedisian School of Medicine, Massachusetts
Mass gatherings create challenges for timely and efficient medical response. Compounded by exceptional noise from cheering crowds and ambient entertainment, compacted audiences form predictable barriers to patient sightings and access. Timely access also may be complicated by steep arena stairwells or poorly-defined locations along a longitudinal raceway, parade, or beachside festival. On-scene responders often encounter fixed barricades, inebriated crowds, obtrusive noise, and relative distances from on-site medical aid centers. Very often, potentially ill or injured persons are adamantly set against leaving their coveted position in the audience having purchased expensive tickets, traveled far and awaited many months, or even years, to be there. Once retrieved, patients need to be conveyed with protective measures and evaluated appropriately despite resource-limited settings and often pervasive heat, humidity and intoxication. Accordingly, patient identification, intra-site retrieval, evacuation, tracking, and communications need to be optimally planned and well-coordinated to mitigate these challenges. Recent experiences have provided evolving insights into best practices for mass gathering medical professionals. Many are addressed within this discussion including definitions for reportable patients, use of spotters and geospatial applications, coordinated tandem response with security personnel, dedicated record-keepers at medical care sites and electronic tracking devices for vulnerable populations and even entire audiences.
Large-scale geological structures have controlled the long-term development of the bed and thus the flow of the West Antarctic Ice Sheet (WAIS). However, complete ice cover has obscured the age and exact positions of faults and geological boundaries beneath Thwaites Glacier and Pine Island Glacier, two major WAIS outlets in the Amundsen Sea sector. Here, we characterize the only rock outcrop between these two glaciers, which was exposed by the retreat of slow-flowing coastal ice in the early 2010s to form the new Sif Island. The island comprises granite, zircon U-Pb dated to ~177–174 Ma and characterized by initial ɛNd, 87Sr/86Sr and ɛHf isotope compositions of -2.3, 0.7061 and -1.3, respectively. These characteristics resemble Thurston Island/Antarctic Peninsula crustal block rocks, strongly suggesting that the Sif Island granite belongs to this province and placing the crustal block's boundary with the Marie Byrd Land province under Thwaites Glacier or its eastern shear margin. Low-temperature thermochronological data reveal that the granite underwent rapid cooling following emplacement, rapidly cooled again at ~100–90 Ma and then remained close to the Earth's surface until present. These data help date vertical displacement across the major tectonic structure beneath Pine Island Glacier to the Late Cretaceous.
Background: New Delhi Metallo-β-lactamase (NDM)–producing Escherichia coli are highly resistant organisms that spread quickly. In the United States, organisms with blaNDM are rare and mostly associated with healthcare settings. However, in other countries, blaNDM can be relatively common and are found in community settings. State veterinary and public health partners detected NDM E. coli in a dog from Iran living at a Wisconsin animal rescue facility (ARF), where 40% of dogs had international origins. We investigated to determine spread among dog and human contacts and prevent further transmission. Methods: We screened dogs and humans at the ARF, a local veterinary clinic (clinic A), and ARF staff homes (homes A and B) for colonization with blaNDM. We reviewed veterinary records and conducted a case–control analysis to identify risk factors for blaNDM acquisition among dogs. We evaluated ARF infection control practices. Screening specimens that were positive for blaNDM were cultured. We conducted an analysis of short- and long-read whole-genome sequencing data to evaluate isolate relatedness. We compared NDM E. coli sequences from dogs to all NDM E. coli sequences from humans collected in Wisconsin and nearby states. Results: Screening identified blaNDM colonization in 27 (37%) of 73 ARF dogs and 4 (56%) of 7 dogs in home A, but not in ARF or staff in clinic A. Among ARF dogs with blaNDM, 20 (74%) 27 had international origins and 22 (81%) had ≥1 medical condition. Dogs sharing the same space (OR, 5.1; 95% CI, 1.8–14.7) were associated with blaNDM acquisition. We observed high animal density, soiled environments, and insufficient hand hygiene. ARF staff wore workwear and work shoes off site, including to home A. Sequencing identified 3 multilocus sequence types (STs) using the Achtman scheme among 27 isolates with blaNDM-5. Most isolates were ST361 (20 of 27, 74%) followed by ST167 (6 of 27, 22%) and ST1163 (1 of 27, 4%). Within-MLST cluster variability was <1–3 high-quality single-nucleotide variant differences, each harboring a ST-specific plasmid with blaNDM-5. No NDM-E. coli sequences from humans appeared related. Conclusions: Investigation of a single isolate led to identification of widespread NDM-E. coli transmission among dogs at an ARF. There were multiple NDM E. coli introductions to the ARF, likely by dogs of international origin. Poor hygiene contributed to transmission among ARF dogs and to dogs outside the ARF. Transmission of blaNDM-5 at the ARF and offsite spread to home A demonstrate the potential for unrecognized community sources to disseminate NDM E. coli in community settings. Strategies and lessons learned from interventions to prevent antibiotic resistance in human healthcare settings may inform and support prevention in animal care.
Ocean-driven melt of Antarctic ice shelves is an important control on mass loss from the ice sheet, but is complex to study due to significant variability in melt rates both spatially and temporally. Here we assess the strengths and weakness of satellite and field-based observations as tools for testing models of ice-shelf melt. We discuss how the complementary use of field, satellite and model data can be a powerful but underutilised tool for studying melt processes. Finally, we identify some community initiatives working to collate and publish coordinated melt rate datasets, which can be used in future for validating satellite-derived maps of melt and evaluating processes in numerical simulations.
There is significant interest in developing early passage cell lines with matched normal reference DNA to facilitate a precision medicine approach in assessing drug response. This study aimed to establish early passage cell lines, and perform whole exome sequencing and short tandem repeat profiling on matched normal reference DNA, primary tumour and corresponding cell lines.
Methods
A cell culture based, in vitro study was conducted of patients with primary human papillomavirus positive and human papillomavirus negative tumours.
Results
Four early passage cell lines were established. Two cell lines were human papillomavirus positive, confirmed by sequencing and p16 immunoblotting. Short tandem repeat profiling confirmed that all cell lines were established from their index tumours. Whole exome sequencing revealed that the matched normal reference DNA was critical for accurate mutational analysis: a high rate of false positive mutation calls were excluded (87.6 per cent).
Conclusion
Early passage cell lines were successfully established. Patient-matched reference DNA is important for accurate cell line mutational calls.
To determine the prevalence of human papillomavirus in paediatric tonsils in Southwestern Ontario, Canada.
Materials and methods
Patients aged 0–18 years undergoing tonsillectomy were recruited. Two specimens (left and right tonsils) were collected from each participant. Tonsillar DNA was analysed using quantitative polymerase chain reaction to determine the presence of human papillomavirus subtypes 6, 11, 16 or 18.
Results
A total of 102 patients, aged 1–18 years (mean age of 5.7 years), were recruited. Ninety-nine surveys were returned. There were 44 females (44.4 per cent) and 55 males (55.6 per cent). Forty patients (40.4 per cent) were firstborn children and 73 (73.7 per cent) were delivered vaginally. Six mothers (6.1 per cent) and one father (1.0 per cent) had prior known human papillomavirus infection, and one mother (1.0 per cent) had a history of cervical cancer. All tonsil specimens were negative for human papillomavirus subtypes 6, 11, 16 and 18.
Conclusion
No human papillomavirus subtypes 6, 11, 16 or 18 were found in paediatric tonsil specimens from Southwestern Ontario.
Interest in cover crops is increasing but information is limited on integrating them into crop rotations especially in the relatively short growing season on the northern Great Plains. A 3-yr research project, initiated in 2009 near Mandan, North Dakota, USA, evaluated (1) what impact cover crops may have on subsequent cash crops yields and (2) whether cover crop mixtures are more productive and provide additional benefits compared to cover crop monocultures. The study evaluated 18 different cover crop monocultures and mixtures that were seeded in August following dry pea (Pisum sativum L.). The following year, spring wheat (Triticum aestivum L.), corn (Zea mays L.), soybean (Glycine max L.) and field pea were seeded into the different cover crop treatments and a non-treated control. A lack of timely precipitation in 2009 resulted in a low cover crop yield of 17 g m2 compared to 100 and 77 g m2 in 2008 and 2010, respectively. Subsequent cash crop yield was not affected by late-seeded cover crops. Cool-season cover crop monocultures were more productive than warm-season monocultures and some mixtures in 2008 and 2010. Relative yield total did not differ from one in any cover crop mixture suggesting that overyielding did not occur. Species selection rather than species diversity was the most important contributor to cover crop yield. Cover crops can be grown following short-season cash crops in the northern Great Plains, but precipitation timing and species selection are critical.
During the 2018/19 Antarctic field season, the British Antarctic Survey (BAS) Basal conditions on Rutford Ice Stream: BEd Access, Monitoring and Ice Sheet History’ (BEAMISH) project drilled three holes through the Rutford Ice Stream, West Antarctica. At up to 2154 m, these are the deepest hot water drilled subglacial access holes yet created, enabling the recovery of sediment from the subglacial environment, and instrumenting the ice stream and its bed. The BEAMISH hot-water drill system was built on extensive experience with the BAS ice shelf hot-water drill and utilises many identical components. With up to 1 MW of heating power available, the hot water drill produces 140 L min−1 of water at 85°C to create a 300 mm diameter access hole to the base of the ice stream. New systems and processes were developed for BEAMISH to aid critical aspects of deep access drilling, most notably the creation of cavities interlinking boreholes at 230 m below the surface and enabling water recirculation throughout the deep drilling operations. The modular design of the BEAMISH drill offers many benefits in its adaptability, redundancy, and minimal logistical footprint. These design features can easily accommodate the modifications needed for future deep, clean access hole creation in the exploration of subglacial environments.
Three holes were drilled to the bed of Rutford Ice Stream, through ice up to 2154 m thick, to investigate the basal processes and conditions associated with fast ice flow and the glacial history of the West Antarctic Ice Sheet. A narrative of the drilling, measuring and sampling activities, as well as some preliminary results and initial interpretations of subglacial conditions, is given. These were the deepest subglacial access holes ever drilled using the hot-water drilling method. Samples of bed and englacial sediments were recovered, and a number of instruments were installed in the ice column and the bed. The ice–bed interface was found to be unfrozen, with an existing, well-developed subglacial hydrological system at high pressure, within ~1% of the ice overburden. The bed itself comprises soft, water-saturated sediments, consistent with previous geophysical interpretations. Englacial sediment quantity varies significantly between two locations ~2 km apart, and possibly over even shorter (~20 m) distances. Difficulties and unusual observations encountered while connecting to the subglacial hydrological system in one hole possibly resulted from the presence of a large clast embedded in the bottom of the ice.
George L. Cowgill had a major influence on the study of the ancient city of Teotihuacan and the development and promotion of quantitative methods in archaeology. His wit, teaching, and research influenced many in the profession. We draw on two published autobiographical works (Cowgill 2008a, 2013a), some unpublished autobiographical notes (Cowgill 1983), his many publications, and our own associations with George.
Several autonomous phase-sensitive radio-echo sounders (ApRES) were deployed at Greenland glaciers to investigate ice deformation. Different attenuation settings were tested and it was observed that, in the presence of clipping of the deramped ApRES signal, each setting produced a different result. Specifically, higher levels of clipping associated with lower attenuation produced an apparent linear increase of diurnal vertical cumulative displacement with depth, and obscured the visibility of the basal reflector in the return amplitude. An example with a synthetic deramped signal confirmed that these types of artifacts result from the introduction of harmonics from square-wave-like features introduced by clipping. Apparent linear increase of vertical displacement with depth occurs when the vertical position of a near-surface internal reflector changes in time. Artifacts in the return amplitude may obscure returns from internal reflectors and the basal reflector, making it difficult to detect thickness evolution of the ice and to correctly estimate vertical velocities. Variations in surface melt during ApRES deployments can substantially modulate the received signal strength on short timescales, and we therefore recommend using higher attenuator settings for deployments in such locations.
We employ global input–output analysis to quantify amplification of exogenous disturbances in compressible boundary layer flows. Using the spatial structure of the dominant response to time-periodic inputs, we explain the origin of steady reattachment streaks in a hypersonic flow over a compression ramp. Our analysis of the laminar shock–boundary layer interaction reveals that the streaks arise from a preferential amplification of upstream counter-rotating vortical perturbations with a specific spanwise wavelength. These streaks are associated with heat-flux striations at the wall near flow reattachment and they can trigger transition to turbulence. The streak wavelength predicted by our analysis compares favourably with observations from two different hypersonic compression ramp experiments. Furthermore, our analysis of inviscid transport equations demonstrates that base-flow deceleration contributes to the amplification of streamwise velocity and that the baroclinic effects are responsible for the production of streamwise vorticity. Finally, the appearance of the temperature streaks near reattachment is triggered by the growth of streamwise velocity and streamwise vorticity perturbations as well as by the amplification of upstream temperature perturbations by the reattachment shock.
Increasing ocean and air temperatures have contributed to the removal of floating ice shelves from several Greenland outlet glaciers; however, the specific contribution of these external forcings remains poorly understood. Here we use atmospheric, oceanographic and glaciological time series data from the ice shelf of Petermann Gletscher, NW Greenland to quantify the forcing of the ocean and atmosphere on the ice shelf at a site ~16 km from the grounding line within a large sub-ice-shelf channel. Basal melt rates here indicate a strong seasonality, rising from a winter mean of 2 m a−1 to a maximum of 80 m a−1 during the summer melt season. This increase in basal melt rates confirms the direct link between summer atmospheric warming around Greenland and enhanced ocean-forced melting of its remaining ice shelves. We attribute this enhanced melting to increased discharge of subglacial runoff into the ocean at the grounding line, which strengthens under-ice currents and drives a greater ocean heat flux toward the ice base.
We propose the concept of the “Fish Revolution” to demarcate the dramatic increase in North Atlantic fisheries after AD 1500, which led to a 15-fold increase of cod (Gadus morhua) catch volumes and likely a tripling of fish protein to the European market. We consider three key questions: (1) What were the environmental parameters of the Fish Revolution? (2) What were the globalising effects of the Fish Revolution? (3) What were the consequences of the Fish Revolution for fishing communities? While these questions would have been considered unknowable a decade or two ago, methodological developments in marine environmental history and historical ecology have moved information about both supply and demand into the realm of the discernible. Although much research remains to be done, we conclude that this was a major event in the history of resource extraction from the sea, mediated by forces of climate change and globalisation, and is likely to provide a fruitful agenda for future multidisciplinary research.
The detection and monitoring of meltwater within firn presents a significant monitoring challenge. We explore the potential of small wireless sensors (ETracer+, ET+) to measure temperature, pressure, electrical conductivity and thus the presence or absence of meltwater within firn, through tests in the dry snow zone at the East Greenland Ice Core Project site. The tested sensor platforms are small, robust and low cost, and communicate data via a VHF radio link to surface receivers. The sensors were deployed in low-temperature firn at the centre and shear margins of an ice stream for 4 weeks, and a ‘bucket experiment’ was used to test the detection of water within otherwise dry firn. The tests showed the ET+ could log subsurface temperatures and transmit the recorded data through up to 150 m dry firn. Two VHF receivers were tested: an autonomous phase-sensitive radio-echo sounder (ApRES) and a WinRadio. The ApRES can combine high-resolution imaging of the firn layers (by radio-echo sounding) with in situ measurements from the sensors, to build up a high spatial and temporal resolution picture of the subsurface. These results indicate that wireless sensors have great potential for long-term monitoring of firn processes.