Spatially Explicit Network Analysis Reveals Multi‐Species Annual Cycle Movement Patterns of Sea Ducks

Conservation of long‐distance migratory species poses unique challenges. Migratory connectivity, that is, the extent to which groupings of individuals at breeding sites are maintained in wintering areas, is frequently used to evaluate population structure and assess use of key habitat areas. However, for species with complex or variable annual cycle movements, this traditional bimodal framework of migratory connectivity may be overly simplistic. Like many other waterfowl, sea ducks often travel to specific pre‐ and post‐breeding sites outside their nesting and wintering areas to prepare for migration by feeding extensively and, in some cases, molting their flight feathers. These additional migrations may play a key role in population structure, but are not included in traditional models of migratory connectivity. Network analysis, which applies graph theory to assess linkages between discrete locations or entities, offers a powerful tool for quantitatively assessing the contributions of different sites used throughout the annual cycle to complex spatial networks. We collected satellite telemetry data on annual cycle movements of 672 individual sea ducks of five species from throughout eastern North America and the Great Lakes. From these data, we constructed a multi‐species network model of migratory patterns and site use over the course of breeding, molting, wintering, and migratory staging. Our results highlight inter‐ and intra‐specific differences in the patterns and complexity of annual cycle movement patterns, including the central importance of staging and molting sites in James Bay, the St. Lawrence River, and southern New England to multi‐species annual cycle habitat linkages, and highlight the value of Long‐tailed Ducks (Calengula haemalis) as an umbrella species to represent the movement patterns of multiple sea duck species. We also discuss potential applications of network migration models to conservation prioritization, identification of population units, and integrating different data streams

Implanted Satellite Transmitters Affect Sea Duck Movement Patterns at Short and Long Timescales

Studies of the effects of transmitters on wildlife often focus on survival. However, sublethal behavioral changes resulting from radio-marking have the potential to affect inferences from telemetry data and may vary based on individual and environmental characteristics. We used a long-term, multi-species tracking study of sea ducks to assess behavioral patterns at multiple temporal scales following implantation of intracoelomic satellite transmitters. We applied state-space models to assess short-term behavioral patterns in 476 individuals with implanted satellite transmitters, as well as comparing breeding site attendance and migratory phenology across multiple years after capture. In the short term, our results suggest an increase in dispersive behavior immediately following capture and transmitter implantation; however, behavior returned to seasonally average patterns within ~5 days after release. Over multiple years, we found that breeding site attendance by both males and females was depressed during the first breeding season after radio-marking relative to subsequent years, with larger relative decreases in breeding site attendance among males than females. We also found that spring and breeding migrations occurred later in the first year after radio-marking than in subsequent years. Across all behavioral effects, the severity of behavioral change often varied by species, sex, age, and capture season. We conclude that, although individuals appear to adjust relatively quickly (i.e. within 1 week) to implanted satellite transmitters, changes in breeding phenology may occur over the longer term and should be considered when analyzing and reporting telemetry data

In Vivo RNAi Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling

We used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic stem and progenitor cells did not affect engraftment, reconstitution, or differentiation. Finally, using an Itgb3 knockout mouse model, we confirmed that Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.National Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant P01 CA108631)National Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant RC1 CA145229)National Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant R01 CA140292)National Institutes of Health (U.S.) (Harvard Stem Cell Institute. GlaxoSmithKline. Grant CA148180

Bounds on the possible evolution of the Gravitational Constant from Cosmological Type-Ia Supernovae

Recent high-redshift Type Ia supernovae results can be used to set new bounds on a possible variation of the gravitational constant $G$. If the local value of $G$ at the space-time location of distant supernovae is different, it would change both the kinetic energy release and the amount of $^{56}$Ni synthesized in the supernova outburst. Both effects are related to a change in the Chandrasekhar mass $M_{Ch} \propto G^{-3/2}$. In addition, the integrated variation of $G$ with time would also affect the cosmic evolution and therefore the luminosity distance relation. We show that the later effect in the magnitudes of Type Ia supernovae is typically several times smaller than the change produced by the corresponding variation of the Chandrasekhar mass. We investigate in a consistent way how a varying $G$ could modify the Hubble diagram of Type Ia supernovae and how these results can be used to set upper bounds to a hypothetical variation of $G$. We find G/G_0 \la 1.1 and G'/G \la 10^{-11} yr^{-1} at redshifts $z\simeq 0.5$. These new bounds extend the currently available constrains on the evolution of $G$ all the way from solar and stellar distances to typical scales of Gpc/Gyr, i.e. by more than 15 orders of magnitudes in time and distance.Comment: 9 pages, 4 figures, Phys. Rev. D. in pres

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

The effects of anatomical errors on shoulder kinematics computed using multi-body models

Joint motion calculated using multi-body models and inverse kinematics presents many advantages over direct marker-based calculations. However, the sensitivity of the computed kinematics is known to be partly caused by the model and could also be influenced by the participants’ anthropometry and sex. This study aimed to compare kinematics computed from an anatomical shoulder model based on medical images against a scaled-generic model and quantify the effects of anatomical errors and participants’ anthropometry on the calculated joint angles. Twelve participants have had planar shoulder movements experimentally captured in a motion lab, and their shoulder anatomy imaged using an MRI scanner. A shoulder multi-body dynamics model was developed for each participant, using both an image-based approach and a scaled-generic approach. Inverse kinematics have been performed using the two different modelling procedures and the three different experimental motions. Results have been compared using Bland–Altman analysis of agreement and further analysed using multi-linear regressions. Kinematics computed via an anatomical and a scaled-generic shoulder models differed in average from 3.2 to 5.4 degrees depending on the task. The MRI-based model presented smaller limits of agreement to direct kinematics than the scaled-generic model. Finally, the regression model predictors, including anatomical errors, sex, and BMI of the participant, explained from 41 to 80% of the kinematic variability between model types with respect to the task. This study highlighted the consequences of modelling precision, quantified the effects of anatomical errors on the shoulder kinematics, and showed that participants' anthropometry and sex could indirectly affect kinematic outcomes.</p

The Use of Glenoid Structural Allografts for Glenoid Bone Defects in Reverse Shoulder Arthroplasty

Background: The use of reverse shoulder arthroplasty as a primary and revision implant is increasing. Advances in implant design and preoperative surgical planning allow the management of complex glenoid defects. As the demand for treating severe bone loss increases, custom allograft composites are needed to match the premorbid anatomy. Baseplate composite structural allografts are used in patients with eccentric and centric defects to restore the glenoid joint line. Preserving bone stock is important in younger patients where a revision surgery is expected. The aim of this article is to present the assessment, planning, and indications of femoral head allografting for bony defects of the glenoid. Methods: The preoperative surgical planning and the surgical technique to execute the plan with a baseplate composite graft are detailed. The preliminary clinical and radiological results of 29 shoulders which have undergone this graft planning and surgical technique are discussed. Clinical outcomes included visual analogue score of pain (VAS), American Shoulder and Elbow Surgeons score (ASES), Constant–Murley score (CS), satisfaction before and after operation, and active range of motion. Radiological outcomes included graft healing and presence of osteolysis or loosening. Results: The use of composite grafts in this series has shown excellent clinical outcomes, with an overall graft complication rate in complex bone loss cases of 8%. Conclusion: Femoral head structural allografting is a valid and viable surgical option for glenoid bone defects in reverse shoulder arthroplasty

Single-Stage Revision Reverse Shoulder Arthroplasty: Preoperative Planning, Surgical Technique, and Mixed Reality Execution

Revision shoulder arthroplasty is increasing with the number of primary shoulder replacements rising globally. Complex primary and revisions of shoulder arthroplasties pose specific challenges for the surgeon, which must be addressed preoperatively and intraoperatively. This article aimed to present strategies for the management of revision of shoulder arthroplasties through a single-stage approach. Preoperatively, patient factors, such as age, comorbidities, and bone quality, should be considered. The use of planning software can aid in accurately evaluating implants in situ and predict bony anatomy that will remain after explantation during the revision surgery. The planning from such software can then be executed with the help of mixed reality technology to allow accurate implant placement. Single-stage revision is performed in two steps (debridement as first step, implantation and reconstruction as the second step), guided by the following principles: adequate debridement while preserving key soft tissue attachments (i.e., rotator cuff, pectoralis major, latissimus dorsi, deltoid), restoration of glenoid joint line using bone grafting, restoration of humeral length, reconstruction and/or reattachment of soft tissues, and strict compliance with the postoperative antibiotic regimen. Preliminary results of single-stage revision shoulder arthroplasty show improvement in patient outcomes (mean 1 year), successful treatment of infection for those diagnosed with periprosthetic joint infection, and improved cost&ndash;benefit parameters for the healthcare system