Is sharing really caring? Viewpoints on shared decision‐making in paediatrics

Shared decision‐making (SDM), the cornerstone of family‐centred care and the gold standard in health decision‐making, occurs when the patient, family members and the health‐care team members partner to make health decisions about the child. This partnership involves an exchange of medical information and information about patient/family preferences and values. Together, the health‐care team, parent and patient deliberate to determine the best course of action for the child. Despite high‐quality evidence supporting its positive impact on outcomes, SDM has not been widely adopted in paediatric clinical practice. Greater understanding of the impact of SDM on all members of the decision triad (parent, patient and health‐care provider) may increase the likelihood of SDM adoption. Therefore, we present the viewpoints of a paediatric patient, parent and paediatrician about the use of SDM. A youth living with a rare chronic disease discusses the impacts of being involved and excluded from health decisions. A mother of a son living with a rare nephrotic condition discusses working with a health‐care team who are committed and skilled in SDM and the positive impacts SDM has had for her son's care. A general paediatrician with research expertise in SDM discusses the individual and system level challenges and rewards of using SDM in her clinical practice. Based on the viewpoints presented, we offer pragmatic recommendations for using SDM in paediatric clinical practice.     

Cerebrovascular inflammation promotes the formation of brain metastases

Brain metastases are the most prevalent intracranial malignancy. Patient outcome is poor and treatment options are limited. Hence, new avenues must be explored to identify potential therapeutic targets. Inflammation is a known critical component of cancer progression. Intratumoral inflammation drives progression and leads to the release of circulating tumor cells (CTCs). Inflammation at distant sites promotes adhesion of CTCs to the activated endothelium and then initiates the formation of metastases. These interactions mostly involve cell adhesion molecules expressed by activated endothelial cells. For example, the vascular cell adhesion molecule-1 (VCAM-1) is known to promote transendothelial migration of cancer cells in different organs. However, it is unclear whether a similar mechanism occurs within the specialized environment of the brain. Our objective was therefore to use molecular imaging to assess the potential role of VCAM-1 in promoting the entry of CTCs into the brain. First, magnetic resonance imaging (MRI) and histological analyses revealed that cerebrovascular inflammation induced by intracranial injection of lipopolysaccharide significantly increased the expression of VCAM-1 in the Balb/c mouse brain. Next, intracardiac injection of 4T1 mammary carcinoma cancer cells in animals with cerebrovascular inflammation yielded a higher brain metastasis burden than in the control animals. Finally, blocking VCAM-1 prior to 4T1 cells injection prevented this increased metastatic burden. Here, we demonstrated that by contributing to CTCs adhesion to the activated cerebrovascular endothelium, VCAM-1 improves the capacity of CTCs to form metastatic foci in the brain.     

Erosion in southern Tibet shut down at ～10 Ma due to enhanced rock uplift within the Himalaya

Exhumation of the southern Tibetan plateau margin reflects interplay between surface and lithospheric dynamics within the Himalaya–Tibet orogen. We report thermochronometric data from a 1.2-km elevation transect within granitoids of the eastern Lhasa terrane, southern Tibet, which indicate rapid exhumation exceeding 1 km/Ma from 17–16 to 12–11 Ma followed by very slow exhumation to the present. We hypothesize that these changes in exhumation occurred in response to changes in the loci and rate of rock uplift and the resulting southward shift of the main topographic and drainage divides from within the Lhasa terrane to their current positions within the Himalaya. At ∼17 Ma, steep erosive drainage networks would have flowed across the Himalaya and greater amounts of moisture would have advected into the Lhasa terrane to drive large-scale erosional exhumation. As convergence thickened and widened the Himalaya, the orographic barrier to precipitation in southern Tibet terrane would have strengthened. Previously documented midcrustal duplexing around 10 Ma generated a zone of high rock uplift within the Himalaya. We use numerical simulations as a conceptual tool to highlight how a zone of high rock uplift could have defeated transverse drainage networks, resulting in substantial drainage reorganization. When combined with a strengthening orographic barrier to precipitation, this drainage reorganization would have driven the sharp reduction in exhumation rate we observe in southern Tibet.The Himalaya–Tibet orogenic system, formed by collision between India and Asia beginning ca. 50 Ma, is the most salient topographic feature on Earth and is considered the archetype for understanding continental collision. Geophysical and geologic research has illuminated the modern structure and dynamics of the orogen (1). Nonetheless, how the relatively low relief and high elevation Tibetan plateau grew spatially and temporally and what underlying mechanism(s) drove the patterns of plateau growth remain outstanding questions.In the internally drained central Tibetan plateau, evidence from carbonate stable isotopes suggest that high elevations persisted since at least 25–35 Ma (2, 3). Sustained high elevations since shortly after collision commenced have also been used to explain low long-term erosion rates in the internally drained plateau interior (4–6). In contrast to the central plateau, the externally drained Tibetan plateau margins serve as the headwaters for many major river systems in Asia. Because externally drained rivers provide an erosive mechanism to destroy uplifted terrane, understanding why these rivers have not incised further and more deeply into the Tibetan plateau is essential to decipher how the plateau grew. Recent research in the eastern (7, 8) and northern (9) Tibetan plateau indicates that erosion rates have increased significantly since ∼10 Ma. These increases suggest that rock uplift rates have also increased and that the plateau has expanded to the east and north during this time [due to lower crustal flow (7) or upper crustal extrusion (8) to the east and structural reorganization to the north (9)], causing rivers to steepen and erode at faster rates.The history of the southern Tibetan plateau margin, on the other hand, is less well understood. The southern Tibetan plateau is presently drained by the Yarlung and Indus Rivers, which each flow parallel to the Himalayan range for more than 1,000 km before descending from the plateau at the Himalayan syntaxes. Evidence from fossils and carbonate stable isotopes suggest that high elevations in the southern Tibetan plateau persisted since at least 15 Ma (10, 11) and potentially even before collision began (12). Additionally, sediments from the Himalayan foreland, Bengal, and Central Myanmar basins require external drainage of the southern Tibetan plateau since at least 14 Ma and potentially as early as 40 Ma (13–15). High elevations and external drainage since at least Middle Miocene time indicate that rock uplift rates in the southern Tibetan plateau may have kept up with the pace of river incision for tens of millions of years. However, cosmogenic nuclide concentrations indicate low erosion rates (typically <10² m/Ma) in both the Indus and Yarlung drainages over the last several hundred thousand years (16, 17). No data yet exist to test whether these slow erosion rates persisted over longer 10⁶- to 10⁷-y timescales. Therefore, it is uncertain how high elevations in the southern plateau have been sustained: are long-term rock uplift and erosion rates both high or have slow erosion rates persisted despite external drainage by some other mechanism?Here, we examine the exhumation history of the eastern part of the Tibetan plateau’s southern margin using thermochronometry, a technique in which thermal histories of rocks are constrained by the evolution of geochemical systems sensitive to temperatures within Earth’s upper crust. We present apatite ⁴He/³He, apatite and zircon (U-Th)/He, and biotite and K-feldspar ⁴⁰Ar/³⁹Ar thermochronometry data from granitic bedrock samples of the Cretaceous–Cenozoic Gangdese batholith in the eastern Lhasa terrane, southern Tibet. Samples were collected along a 1.2-km elevation transect near the eastern headwaters of the Lhasa River, a major tributary of the Yarlung River (Fig. 1 and SI Appendix, Table S1). This approach is advantageous for several reasons. First, by using a suite of thermochronometric systems sensitive to temperatures ranging from ∼30 °C to 350 °C, we can identify changes in exhumation rate over a longer duration than would be possible with any subset of them. Second, sampling along an elevation transect leverages the fact that rocks at different elevations within a pluton share a similar exhumation history but have different cooling histories. Resolvable differences in the cooling histories between rocks at different elevations can more tightly constrain the overall exhumation history than the cooling history of a single elevation sample. Third, to avoid the effects of local-scale tectonic exhumation, we collected samples in a location that is not in the footwall of one of the north-south trending rift systems in southern Tibet. Therefore, the data primarily record temporal trends in erosional exhumation of the region. With data from this sampling scheme, we use 3D thermokinematic models to constrain the timing of both large-scale unroofing of the Gangdese batholith and local, kilometer-scale relief development due to river incision. From these data and thermokinematic models, we develop a hypothesis for landscape evolution within the southern Tibetan plateau that we illustrate schematically using a simple numerical model.Open in a separate windowFig. 1.(A) Topography and (B) mean annual precipitation (MAP) in southern Tibet and the Himalaya. The yellow star marks the city of Lhasa and blue circles denote the sample locations. The following generalized geologic structures are also shown in A: GCT, Great Counter Thrust; GT, Gangdese Thrust; IYSZ, Indus-Yarlung Suture Zone; MBT, Main Boundary Thrust; MCT, Main Central Thrust; MFT, Main Frontal Thrust; STD, South Tibetan Detachment; WF, Woka fault. In B, major river networks draining the southern Tibetan plateau and Himalaya are shown in black, with the Yarlung River and the Lhasa River highlighted in white and tan, respectively. C shows a detailed view of our sample locations and the surrounding topography. Topography plotted from 90 m SRTM (Shuttle Radar Topography Mission) data; MAP plotted from TRMM (Tropical Rainfall Measurement Mission) 2B31 data collected between 1998 and 2009 (36); geologic structures based on Styron et al. (30), Decelles et al. (31), Yin et al. (33), and Hodges (44).