Mobile accelerometry is a powerful and promising option to capture long-term changes in gait in both clinical and real-world scenarios. Increasingly, gait parameters have demonstrated their value as ...clinical outcome parameters, but validation of these parameters in elderly patients is still limited.
The aim of this study was to implement a validation framework appropriate for elderly patients and representative of real-world settings, and to use this framework to test and improve algorithms for mobile accelerometry data in an orthogeriatric population.
Twenty elderly subjects wearing a 3D-accelerometer completed a parcours imitating a real-world scenario. High-definition video and mobile reference speed capture served to validate different algorithms.
Particularly at slow gait speeds, relevant improvements in accuracy have been achieved. Compared to the reference the deviation was less than 1% in step detection and less than 0.05 m/s in gait speed measurements, even for slow walking subjects (< 0.8 m/s).
With the described setup, algorithms for step and gait speed detection have successfully been validated in an elderly population and demonstrated to have improved performance versus previously published algorithms. These results are promising that long-term and/or real-world measurements are possible with an acceptable accuracy even in elderly frail patients with slow gait speeds.
PIK3CA-related disorders include vascular malformations and overgrowth of various tissues that are caused by postzygotic, somatic variants in the gene encoding phosphatidylinositol-3-kinase (PI3K) ...catalytic subunit alpha. These mutations result in activation of the PI3K/AKT/mTOR signaling pathway. The goals of this review are to provide education on the underlying mechanism of disease for this group of rare conditions and to summarize recent advancements in the understanding of, as well as current and emerging treatment options for PIK3CA-related disorders. Management of patients with PIK3CA-related disorders requires a multidisciplinary approach. Further results from ongoing clinical studies of agents targeting the PI3K pathway are highly anticipated.
Phenotype-based diagnostic criteria were developed for Proteus syndrome in 1999 and updated in 2006. Subsequently, the causative mosaic gene alteration was discovered, the c.49G>A p.E17K variant in ...AKT1. As well, a number of overlapping overgrowth disorders attributable to mosaic PIK3CA variants have now been characterized, leading to the designation of PIK3CA-related overgrowth spectrum (PROS). Finally, ongoing work to better characterize Proteus syndrome has led to identification of additional features of that disorder that could be useful in diagnostic criteria. We have taken the opportunity of these discoveries to re-evaluate the Proteus syndrome diagnostic criteria. Here we propose a new set of diagnostic criteria that establishes a weighted, point-based system for the phenotypic attributes and then integrates that with the potential molecular test results to result in one of two designations: AKT1-related Proteus syndrome or AKT1-related overgrowth spectrum. A patient whose only manifestation is an AKT1 c.49G>A-positive tumor would receive neither of these designations. Here we review the rational basis of diagnostic criteria and argue that a unitary diagnostic entity is a distinct gene-phenotype dyad and that this should be the model for all mendelian disorders. The gene-alone or phenotype-alone approach is inadequate to rigorously delineate a unitary diagnostic entity.
Context.
Shadows in scattered light images of protoplanetary disks are a common feature and support the presence of warps or misalignments between disk regions. These warps are possibly caused by an ...inclined (sub-)stellar companion embedded in the disk.
Aims.
We aim to study the morphology of the protoplanetary disk around the Herbig Ae star HD 139614 based on the first scattered light observations of this disk, which we model with the radiative transfer code
MCMax3D
.
Methods.
We obtained
J
- and
H
-band observations that show strong azimuthal asymmetries in polarized scattered light with VLT/SPHERE. In the outer disk, beyond ~30 au, a broad shadow spans a range of ~240 deg in position angle, in the east. A bright ring at ~16 au also shows an azimuthally asymmetric brightness, with the faintest side roughly coincidental with the brightest region of the outer disk. Additionally, two arcs are detected at ~34 and ~50 au. We created a simple four-zone approximation to a warped disk model of HD 139614 in order to qualitatively reproduce these features. The location and misalignment of the disk components were constrained from the shape and location of the shadows they cast.
Results.
We find that the shadow on the outer disk covers a range of position angles too wide to be explained by a single inner misaligned component. Our model requires a minimum of two separate misaligned zones – or a continuously warped region – to cast this broad shadow on the outer disk. A small misalignment of ~4° between adjacent components can reproduce most of the observed shadow features.
Conclusions.
Multiple misaligned disk zones, potentially mimicking a warp, can explain the observed broad shadows in the HD 139614 disk. A planetary mass companion in the disk, located on an inclined orbit, could be responsible for such a feature and for the dust-depleted gap responsible for a dip in the SED.
Context. While planet formation is thought to occur early in the history of a protoplanetary disk, the presence of planets embedded in disks, or of other processes driving disk evolution, might be ...traced from their imprints on the disk structure. Aims. We study the morphology of the disk around the T Tauri star HD 143006, located in the ~5–11 Myr-old Upper Sco region, and we look for signatures of the mechanisms driving its evolution. Methods. We observed HD 143006 in polarized scattered light with VLT/SPHERE at near-infrared (J-band, 1.2 μm) wavelengths, reaching an angular resolution of ~0.037′′ (~6 au). We obtained two datasets, one with a 145 mas diameter coronagraph, and the other without, enabling us to probe the disk structure down to an angular separation of ~0.06′′ (~10 au). Results. In our observations, the disk of HD 143006 is clearly resolved up to ~0.5′′ and shows a clear large-scale asymmetry with the eastern side brighter than the western side. We detect a number of additional features, including two gaps and a ring. The ring shows an overbrightness at a position angle (PA) of ~140°, extending over a range in position angle of ~60°, and two narrow dark regions. The two narrow dark lanes and the overall large-scale asymmetry are indicative of shadowing effects, likely due to a misaligned inner disk. We demonstrate the remarkable resemblance between the scattered light image of HD 143006 and a model prediction of a warped disk due to an inclined binary companion. The warped disk model, based on the hydrodynamic simulations combined with three-dimensional radiative transfer calculations, reproduces all major morphological features. However, it does not account for the observed overbrightness at PA ~ 140°. Conclusions. Shadows have been detected in several protoplanetary disks, suggesting that misalignment in disks is not uncommon. However, the origin of the misalignment is not clear. As-yet-undetected stellar or massive planetary companions could be responsible for them, and naturally account for the presence of depleted inner cavities.
Increased risk of thromboembolism has been recognized in individuals with mosaic overgrowth disorders, Proteus syndrome (PS) and PIK3CA-related overgrowth spectrum (PROS), including Klippel-Trenaunay ...syndrome and CLOVES syndrome. PS and PROS have distinct, yet overlapping clinical findings and are caused by somatic pathogenic variants in the PI3K/AKT gene signaling pathway. PS is caused by a single somatic activating AKT1 c.49G > A p.E17K variant while PROS can be caused one of multiple variants in PIK3CA. The role of prothrombotic factors, endothelial cell adhesion molecules, and vascular malformations in both PS and PROS have not been previously investigated. A pilot study of prospective clinical and laboratory evaluations with the purposes of identifying potential risk factors for thrombosis was conducted. Doppler ultrasounds and magnetic resonance angiogram/ venography (MRA/MRV) scans identified vascular malformations in PS and PROS that were not appreciated on physical examination. Abnormal D-dimers (0.60-2.0 mcg/ml) occurred in half of individuals, many having vascular malformations, but no thromboses. Soluble vascular endothelial markers, including thrombomodulin, soluble vascular adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), E-selectin, and P-selectin were significantly higher in PS and PROS compared to controls. However, no single attribute was identified that explained the risk of thrombosis. Predisposition to thrombosis is likely multifactorial with risk factors including chronic stasis within vascular malformations, stasis from impaired mobility (e.g., following surgery), decreased anticoagulant proteins, and effects of AKT1 and PIK3CA variants on vascular endothelium. Based on our findings, we propose clinical recommendations for surveillance of thrombosis in PS and PROS.
Context.
Young nearby stars are good candidates in the search for planets with both radial velocity (RV) and direct imaging techniques. This, in turn, allows for the computation of the giant planet ...occurrence rates at all separations. The RV search around young stars is a challenge as they are generally faster rotators than older stars of similar spectral types and they exhibit signatures of magnetic activity (spots) or pulsation in their RV time series. Specific analyses are necessary to characterize, and possibly correct for, this activity.
Aims.
Our aim is to search for planets around young nearby stars and to estimate the giant planet (GP) occurrence rates for periods up to 1000 days.
Methods.
We used the HARPS spectrograph on the 3.6 m telescope at La Silla Observatory to observe 89
A
−
M
young (<600 Myr) stars. We used our SAFIR (Spectroscopic data via Analysis of the Fourier Interspectrum Radial velocities) software to compute the RV and other spectroscopic observables. Then, we computed the companion occurrence rates on this sample.
Results.
We confirm the binary nature of HD 177171, HD 181321 and HD 186704. We report the detection of a close low mass stellar companion for HIP 36985. No planetary companion was detected. We obtain upper limits on the GP (<13
M
Jup
) and BD (∈ 13;80
M
Jup
) occurrence rates based on 83 young stars for periods less than 1000 days, which are set, 2
−2
+3
and 1
−1
+3
%.
Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These phenotypically heterogeneous ...entities have been grouped as PIK3CA‐Related Overgrowth Spectrum disorders (PROS). Deep sequencing technologies have facilitated detection of low‐level mosaic, often necessitating testing of tissues other than blood. Since clinical management practices vary considerably among healthcare professionals and services across different countries, a consensus on management guidelines is needed. Clinical heterogeneity within this spectrum leads to challenges in establishing management recommendations, which must be based on patient‐specific considerations. Moreover, as most of these conditions are rare, affected families may lack access to the medical expertise that is needed to help address the multi‐system and often complex medical issues seen with PROS. In March 2019, macrocephaly‐capillary malformation (M‐CM) patient organizations hosted an expert meeting in Manchester, United Kingdom, to help address these challenges with regards to M‐CM syndrome. We have expanded the scope of this project to cover PROS and developed this consensus statement on the preferred approach for managing affected individuals based on our current knowledge.
XXX.
PDF
