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It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Müller Ice Cap sits on Umingmat Nunaat (Axel Heiberg Island), Nunavut, Canada, ~ 80°N. Its high latitude and elevation suggest it experiences relatively little melt and preserves an undisturbed paleoclimate record. Here, we present a suite of field measurements, complemented by remote sensing, that constrain the ice thickness, accumulation rate, temperature, ice-flow velocity, and surface-elevation change of Müller Ice Cap. These measurements show that some areas near the top of the ice cap are more than 600 m thick, have nearly stable surface elevation, and flow slowly, making them good candidates for an ice core. The current mean annual surface temperature is −19.6 °C, which combined with modeling of the temperature profile indicates that the ice is frozen to the bed. Modeling of the depth-age scale indicates that Pleistocene ice is likely to exist with measurable resolution (300–1000 yr m−1) 20–90 m from the bed, assuming that Müller Ice Cap survived the Holocene Climatic Optimum with substantial ice thickness (~400 m or more). These conditions suggest that an undisturbed Holocene climate record could likely be recovered from Müller Ice Cap. We suggest 91.795°W, 79.874°N as the most promising drill site.
Identify risk factors for central line-associated bloodstream infections (CLABSI) in pediatric intensive care settings in an era with high focus on prevention measures.
Design:
Matched, case–control study.
Setting:
Quaternary children’s hospital.
Patients:
Cases had a CLABSI during an intensive care unit (ICU) stay between January 1, 2015 and December 31, 2020. Controls were matched 4:1 by ICU and admission date and did not develop a CLABSI.
Methods:
Multivariable, mixed-effects logistic regression.
Results:
129 cases were matched to 516 controls. Central venous catheter (CVC) maintenance bundle compliance was >70%. Independent CLABSI risk factors included administration of continuous non-opioid sedative (adjusted odds ratio (aOR) 2.96, 95% CI [1.16, 7.52], P = 0.023), number of days with one or more CVC in place (aOR 1.42 per 10 days [1.16, 1.74], P = 0.001), and the combination of a chronic CVC with administration of parenteral nutrition (aOR 4.82 [1.38, 16.9], P = 0.014). Variables independently associated with lower odds of CLABSI included CVC location in an upper extremity (aOR 0.16 [0.05, 0.55], P = 0.004); non-tunneled CVC (aOR 0.17 [0.04, 0.63], P = 0.008); presence of an endotracheal tube (aOR 0.21 [0.08, 0.6], P = 0.004), Foley catheter (aOR 0.3 [0.13, 0.68], P = 0.004); transport to radiology (aOR 0.31 [0.1, 0.94], P = 0.039); continuous neuromuscular blockade (aOR 0.29 [0.1, 0.86], P = 0.025); and administration of histamine H2 blocking medications (aOR 0.17 [0.06, 0.48], P = 0.001).
Conclusions:
Pediatric intensive care patients with chronic CVCs receiving parenteral nutrition, those on non-opioid sedative infusions, and those with more central line days are at increased risk for CLABSI despite current prevention measures.
Paquimé (also known as Casas Grandes), situated in northern Chihuahua between Mesoamerican and Ancestral Puebloan groups, was a vibrant multicultural centre during the thirteenth and fourteenth centuries AD. Substantial debate surrounds the social organisation of Paquimé's inhabitants. Here, the authors report on the analysis of ancient DNA from a unique child burial beneath a central support post of a room in the House of the Well. They argue that the close genetic relationship of the child's parents, revealed through this analysis, and the special depositional context of the burial reflect one family's attempts to consolidate and legitimise their social standing in this ancient community.
The seemingly idiosyncratic behavior of numerals in Russian and other Slavic languages has long puzzled linguists. This entry describes the core phenomena, taking Russian as a point of departure. Significant differences in other Slavic languages are also identified, since a central problem of analysis is how variation across Slavic might be accommodated. The core data issues concern case and agreement, the former with respect to the phrase containing the numeral, the latter both internal to the numeral phrase as well as between it and the predicate. Related phenomena exhibited by other quantity expressions are also presented. In the course of the presentation, several conceptual approaches are briefly identified, and the reader is directed to relevant research.
Loess paleoenvironmental reconstructions on regional to supra-regional scales have recently gained much attention. Geochemistry comparisons in relation to reference datasets, such as the Upper Continental Crust (UCC) data, have furthered our understanding of the climatic and geomorphological conditions under which terrestrial sites have developed. However, UCC data differs from loess, thereby obscuring important features, and the existing “average loess” datasets also are not sufficient for modern investigations.
In this study, we examine the youngest Polish loess (L1LL1 = MIS 2, ca. 26–15 ka) for its suitability as a new, loess-focused reference dataset. Eighty-nine samples from seven sites were analyzed, using inductively coupled plasma spectrometry. The loess had assumedly been homogenized during transportation and/or sedimentary recycling (LaN/SmN = 3.34–4.06, median 3.78; Eu/Eu* = 0.46–0.66, median 0.55; GdN/YbN = 1.08–1.49, median 1.26), and weakly affected by pre- or post-depositional weathering (CIA = 53.64–69.12, median 57.69). The statistically significant differences between sites in elemental medians were mostly conditioned by variations in grain size and in the “fresh” to “re-deposited” sediment ratio. Nonetheless, the overall geochemical composition homogeneity provided a basis for the estimation of Polish Median Loess (PML) data, as determined for 41 chemical elements. When used, PML data highlight differences between loess regions in Europe, thereby providing a tool for cross-continental comparisons.
In this controlled study, we found that exposure to ultraviolet-C (UV-C) radiation was able to arrest the growth of selected pathogenic enteric and nonfermenting Gram-negative rods. Further studies are needed to confirm the clinical efficacy and determine optimal implementation strategies for utilizing UV-C terminal disinfection.
Ice shelves, which regulate ice flow from the Antarctic ice sheet towards the ocean, are shaped by spatiotemporal patterns of surface accumulation, surface/basal melt and ice dynamics. Therefore, an ice dynamic and accumulation history are imprinted in the internal ice stratigraphy, which can be imaged by radar in the form of internal reflection horizons (IRHs). Here, IRHs were derived from radar data combined across radar platforms (airborne and ground-based) in coastal eastern Dronning Maud Land (East Antarctica), comprising three ice rises and adjacent two ice shelves. To facilitate interpretation of dominant spatiotemporal patterns of processes shaping the local IRH geometry, traced IRHs are classified into three different types (laterally continuous, discontinuous or absent/IRH-free). Near-surface laterally continuous IRHs reveal local accumulation patterns, reflecting the mean easterly wind direction, and correlate with surface slopes. Areas of current and past increased ice flow and internal deformation are marked by discontinuous or IRH-free zones, and can inform about paleo ice-stream dynamics. The established IRH datasets extend continent-wide mapping efforts of IRHs to an important and climatically sensitive ice marginal region of Antarctica and are ready for integration into ice-flow models to improve predictions of Antarctic ice drainage.
Peer support interventions for dietary change may offer cost-effective alternatives to interventions led by health professionals. This process evaluation of a trial to encourage the adoption and maintenance of a Mediterranean diet in a Northern European population at high CVD risk (TEAM-MED) aimed to investigate the feasibility of implementing a group-based peer support intervention for dietary change, positive elements of the intervention and aspects that could be improved. Data on training and support for the peer supporters; intervention fidelity and acceptability; acceptability of data collection processes for the trial and reasons for withdrawal from the trial were considered. Data were collected from observations, questionnaires and interviews, with both peer supporters and trial participants. Peer supporters were recruited and trained to result in successful implementation of the intervention; all intended sessions were run, with the majority of elements included. Peer supporters were complimentary of the training, and positive comments from participants centred around the peer supporters, the intervention materials and the supportive nature of the group sessions. Attendance at the group sessions, however, waned over the intervention, with suggested effects on intervention engagement, enthusiasm and group cohesion. Reduced attendance was reportedly a result of meeting (in)frequency and organisational concerns, but increased social activities and group-based activities may also increase engagement, group cohesion and attendance. The peer support intervention was successfully implemented and tested, but improvements can be suggested and may enhance the successful nature of these types of interventions. Some consideration of personal preferences may also improve outcomes.
This chapter assesses the political impact of the Sustainable Development Goals on global governance. We start by discussing the range of expectations for global governance arrangements, considering the stated objectives of the goals. We then assess the early performance of governance arrangements in terms of shifts in policy and practice against these expectations. Our research shows the impact of the Sustainable Development Goals is largely discursive, with limited transformative outcomes on governance practices. The High-level Political Forum, created to assess global progress towards the implementation of the goals, has failed to provide political leadership and promote coherence across the United Nations system. Our research also shows that the Sustainable Development Goals initiated peer-learning among governments and other actors, yet with limited evidence that this has led to structural transformation towards sustainability. As certain ambitions of the Global Goals have been part of ongoing debates in global governance, our review finally highlights that observable changes often reflect long-term reform trajectories that are not causally linked to the launch of the goals.
OBJECTIVES/GOALS: Current approaches to drug development for the aggressive triple negative breast cancer rely on current 2D and 3D in vitro models which have limited capabilities. We have developed a translational microphysiological system that can maintain the human breast microenvironment to capture the complex interaction with the tumor microenvironment. METHODS/STUDY POPULATION: Three different TNBC cell lines were seeded in BC-MPS: MDA-MB-231 parental cell line, MDA-MB-231wiht the gene, LKB1 overexpressed, which is a tumor suppressor, and MDA-MB-231 with the enzyme, ERK5, an enzyme associated with increased metastasis and drug resistance, knocked out. These three TNBC cell lines were cultured in a standard 2D 96-well plate and in BC-MPS. Time-lapse videos were taken to track cellular mobility. RNA-sequencing was performed to compare different expression levels of various cancer related genes of the cell lines cultured in standard 2D and BC-MPS. RESULTS/ANTICIPATED RESULTS: The LKB1 overexpressed MDA-MB-231 and the ERK5-ko MDA-MB-231 cell lines are expected to have decreased mobility compared to the parental cells. The cell lines are expected to have increased expression of cancer related genes when cultured in BC-MPS than when cultured in standard 2D due to the presence of human breast tissue. DISCUSSION/SIGNIFICANCE: BC-MPS is a promising new translational MPS that facilitates studying long term interactions between real human breast tissue and cancer cells. The BC-MPS systems ability to support the growth of established cell lines has been demonstrated. Future studies will focus on developing the model for personalized medicine.
During the past 20 years, multi-channel radar emerged as a key tool for deciphering an ice sheet's internal architecture. To assign ages to radar reflections and connect them over large areas in the ice sheet, the layer genesis has to be understood on a microphysical scale. Synthetic radar trace modelling based on the dielectric profile of ice cores allows for the assignation of observed physical properties’ variations on the decimetre scale to radar reflectors extending from the coring site to a regional or even whole-ice-sheet scale. In this paper we rely on the available dielectric profiling data of the northern Greenland deep ice cores: NGRIP, NEEM and EGRIP. The three records are well suited for assigning an age model to the stratigraphic radar-mapped layers, and linking up the reflector properties to observations in the cores. Our modelling results show that the internal reflections are mainly due to conductivity changes. Furthermore, we deduce fabric characteristics at the EGRIP drill site from two-way-travel-time differences of along and across-flow polarized radarwave reflections of selected horizons (below 980 m). These indicate in deeper parts of the ice column an across-flow concentrated c-axis fabric.
Exoskeletons that assist the hip, knee, and ankle joints have begun to improve human mobility, particularly by reducing the metabolic cost of walking. However, direct comparisons of optimal assistance of these joints, or their combinations, have not yet been possible. Assisting multiple joints may be more beneficial than the sum of individual effects, because muscles often span multiple joints, or less effective, because single-joint assistance can indirectly aid other joints. In this study, we used a hip–knee–ankle exoskeleton emulator paired with human-in-the-loop optimization to find single-joint, two-joint, and whole-leg assistance that maximally reduced the metabolic cost of walking. Hip-only and ankle-only assistance reduced the metabolic cost of walking by 26 and 30% relative to walking in the device unassisted, confirming that both joints are good targets for assistance (N = 3). Knee-only assistance reduced the metabolic cost of walking by 13%, demonstrating that effective knee assistance is possible (N = 3). Two-joint assistance reduced the metabolic cost of walking by between 33 and 42%, with the largest improvements coming from hip-ankle assistance (N = 3). Assisting all three joints reduced the metabolic cost of walking by 50%, showing that at least half of the metabolic energy expended during walking can be saved through exoskeleton assistance (N = 4). Changes in kinematics and muscle activity indicate that single-joint assistance indirectly assisted muscles at other joints, such that the improvement from whole-leg assistance was smaller than the sum of its single-joint parts. Exoskeletons can assist the entire limb for maximum effect, but a single well-chosen joint can be more efficient when considering additional factors such as weight and cost.
Adhering to a Mediterranean diet (MD) is associated with reduced CVD risk. This study aimed to explore methods of increasing MD adoption in a non-Mediterranean population at high risk of CVD, including assessing the feasibility of a developed peer support intervention. The Trial to Encourage Adoption and Maintenance of a MEditerranean Diet was a 12-month pilot parallel group RCT involving individuals aged ≥ 40 year, with low MD adherence, who were overweight, and had an estimated CVD risk ≥ 20 % over ten years. It explored three interventions, a peer support group, a dietician-led support group and a minimal support group to encourage dietary behaviour change and monitored variability in Mediterranean Diet Score (MDS) over time and between the intervention groups, alongside measurement of markers of nutritional status and cardiovascular risk. 118 individuals were assessed for eligibility, and 75 (64 %) were eligible. After 12 months, there was a retention rate of 69 % (peer support group 59 %; DSG 88 %; MSG 63 %). For all participants, increases in MDS were observed over 12 months (P < 0·001), both in original MDS data and when imputed data were used. Improvements in BMI, HbA1c levels, systolic and diastolic blood pressure in the population as a whole. This pilot study has demonstrated that a non-Mediterranean adult population at high CVD risk can make dietary behaviour change over a 12-month period towards an MD. The study also highlights the feasibility of a peer support intervention to encourage MD behaviour change amongst this population group and will inform a definitive trial.
Two phases of archaeological investigation were performed in the Novi Sad City Museum at Petrovaradin Fortress. In this study, we summarize the results of geo-archaeological investigations of the second period of excavation inside the Novi Sad City Museum building. The fortress is situated on a Danube terrace with the top of the bedrock at ca.123 m asl. The investigated section consists of undisturbed fine-sandy silt. The grain-size distribution of the sediments indicates clearly its alluvial reworking but shows also a general similarity with typical primary loess in the region. All analyzed proxies indicate slightly stronger weathering in the upper part of the profile. Luminescence ages suggest that the investigated sequence covers the last glacial period and the terrace presumably formed during MIS 4. Subsequently, the Danube started its incision at the start of the next warmer period (MIS 3) onward. This terrace age and elevation enable us to derive an uplift rate of the terrace of ca. 0.73 mm/a for the last 60 ka, which seems to increase towards the present. Basal loessic material, in which artifacts occur, likely in the reworked position, indicate that the area close to today's Petrovaradin Fortress was already inhabited in MIS 5.
Ever since the first deep ice cores were drilled, it has been a challenge to determine their original, in-situ orientation. In general, the orientation of an ice core is lost as the drill is free to rotate during transport to the surface. For shallow ice cores, it is usually possible to match the adjacent core breaks, which preserves the orientation of the ice column. However, this method fails for deep ice cores, such as the EastGRIP ice core in Northeast Greenland. We provide a method to reconstruct ice core orientation using visual stratigraphy and borehole geometry. As the EastGRIP ice core is drilled through the Northeast Greenland Ice Stream, we use information about the directional structures to perform a full geographical re-orientation. We compared the core orientation with logging data from core break matching and the pattern of the stereographic projections of the crystals’ c-axis orientations. Both comparisons agree very well with the proposed orientation method. The method works well for 441 out of 451 samples from a depth of 1375–2120 m in the EastGRIP ice core. It can also be applied to other ice cores, providing a better foundation for interpreting physical properties and understanding the flow of ice.
Growers desire more techniques to control weeds in horticultural crops that are grown organically and consumed directly, such as red raspberry. Abrasive grit emited via high air pressure is a new method for controlling weeds. Grit derived from corn cobs was examined for its efficacy during the year of raspberry establishment for 2 to 3 years at three sites (seven site-years) and compared with efficacy of hand-weeding as well as no weed control. Grit was applied once or twice weekly after raspberry transplantation in spring until weed emergence ceased in mid to late July. Weeds and raspberry growth were assessed in August. Grit was effective in controlling broadleaf weeds, averaging 94% control across site-years, but control of grass weeds was less than 10%. Total weed (broadleaf plus grass) control across site-years ranged from 51% to 96% and averaged 78%. Raspberry cane growth was affected by weeds, and grit-weeding at least partially alleviated these effects. Thus, abrasive grit allows growers to manage broadleaf weeds effectively without herbicides or soil tillage. However, additional research is needed to determine the correct amounts and timing of grit applications, as well as more efficacious types of grit, to control grass weeds.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
Methods:
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Results:
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
Conclusions:
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
The Northeast Greenland Ice Stream (NEGIS) is an important dynamic component for the total mass balance of the Greenland ice sheet, as it reaches up to the central divide and drains 12% of the ice sheet. The geometric boundary conditions and in particular the nature of the subglacial bed of the NEGIS are essential to understand its ice flow dynamics. We present a record of more than 8000 km of radar survey lines of multi-channel, ultra-wideband radio echo sounding data covering an area of 24 000 km2, centered on the drill site for the East Greenland Ice-core Project (EGRIP), in the upper part of the NEGIS catchment. Our data yield a new detailed model of ice-thickness distribution and basal topography in the region. The enhanced resolution of our bed topography model shows features which we interpret to be caused by erosional activity, potentially over several glacial–interglacial cycles. Off-nadir reflections from the ice–bed interface in the center of the ice stream indicate a streamlined bed with elongated subglacial landforms. Our new bed topography model will help to improve the basal boundary conditions of NEGIS prescribed for ice flow models and thus foster an improved understanding of the ice-dynamic setting.