Problems and hopes perceived by mothers,fathers and physicians of children receiving palliative care

Background

The quality of shared decision making for children with serious illness may depend on whether parents and physicians share similar perceptions of problems and hopes for the child.

Objective

(i) Describe the problems and hopes reported by mothers, fathers and physicians of children receiving palliative care; (ii) examine the observed concordance between participants; (iii) examine parental perceived agreement; and (iv) examine whether parents who identified specific problems also specified corresponding hopes, or whether the problems were left ‘hopeless’.

Method

Seventy‐one parents and 43 physicians were asked to report problems and hopes and perceived agreement for 50 children receiving palliative care. Problems and hopes were classified into eight domains. Observed concordance was calculated between parents and between each parent and the physicians.

Results

The most common problem domains were physical body (88%), quality of life (74%) and medical knowledge (48%). The most common hope domains were quality of life (88%), suffering (76%) and physical body (39%). Overall parental dyads demonstrated a high percentage of concordance (82%) regarding reported problem domains and a lower percentage of concordance on hopes (65%). Concordance between parents and physicians regarding specific children was lower on problem (65–66%) and hope domains (59–63%). Respondents who identified problems regarding a child's quality of life or suffering were likely to also report corresponding hopes in these domains (93 and 82%, respectively).

Conclusion

Asking parents and physicians to talk about problems and hopes may provide a straightforward means to improve the quality of shared decision making for critically ill children.     

Integrin β3 Haploinsufficiency Modulates Serotonin Transport and Antidepressant-Sensitive Behavior in Mice

Converging lines of evidence have identified genetic interactions between the serotonin transporter (SERT) gene and ITGB3, which encodes the β3 subunit that forms the αIIbβ3 and αvβ3 integrin receptor complexes. Here we examine the consequences of haploinsufficiency in the mouse integrin β3 subunit gene (Itgb3) on SERT function and selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (SSRI) effectiveness in vivo. Biochemical fractionation studies and immunofluorescent staining of murine brain slices reveal that αvβ3 receptors and SERTs are enriched in presynaptic membranes from several brain regions and that αvβ3 colocalizes with a subpopulation of SERT-containing synapses in raphe nuclei. Notably, we establish that loss of a single allele of Itgb3 in murine neurons is sufficient to decrease 5-HT uptake by SERT in midbrain synaptosomes. Pharmacological assays to elucidate the αvβ3-mediated mechanism of reduced SERT function indicate that decreased integrin β3 subunit expression scales down the population size of active SERT molecules and, as a consequence, lowers the effective dose of SSRIs. These data are consistent with the existence of a subpopulation of SERTs that are tightly modulated by integrin αvβ3 and significantly contribute to global SERT function at 5-HT synapses in the midbrain. Importantly, our screen of a normal human population for single nucleotide polymorphisms in human ITGB3 identified a variant associated with reductions in integrin β3 expression levels that parallel our mouse findings. Thus, polymorphisms in human ITGB3 may contribute to the differential responsiveness of select patients to SSRIs.     

Clinical issues in renal transplantation in the elderly

Kidney transplantation is the best renal replacement therapy option and is superior to dialysis in elderly end‐stage renal disease (ESRD) patients. Furthermore, the outcome of transplantation in the elderly is comparable to younger patients in terms of allograft survival. The exact nature of this phenomenon is not completely clear. As the elderly population continues to grow, it becomes more important to identify specific issues associated with kidney transplantation. In particular, elderly transplant recipients might have a lower chance of acute rejection as their immune systems seem to be less reactive. This might predispose elderly recipients to greater risk of post‐transplant infectious complications or malignancies. Furthermore, due to differences in pharmacokinetics, elderly recipients might require lower doses of immunosuppressive medication. As the main cause of graft failure in the elderly is death with a functioning graft and also considering the scarcity of donor organs, it might make sense to recommend transplanting elderly recipients with extended criteria donor kidneys. This approach would balance shorter patient survival compared to younger recipients. In conclusion, old age should not preclude ESRD patients from kidney transplantation. However, specific differences that have to do with immunosuppression and other aspects of managing elderly transplant recipients should be considered.     

Age of Barrier Canyon-style rock art constrained by cross-cutting relations and luminescence dating techniques

Rock art compels interest from both researchers and a broader public, inspiring many hypotheses about its cultural origin and meaning, but it is notoriously difficult to date numerically. Barrier Canyon-style (BCS) pictographs of the Colorado Plateau are among the most debated examples; hypotheses about its age span the entire Holocene epoch and previous attempts at direct radiocarbon dating have failed. We provide multiple age constraints through the use of cross-cutting relations and new and broadly applicable approaches in optically stimulated luminescence dating at the Great Gallery panel, the type section of BCS art in Canyonlands National Park, southeastern Utah. Alluvial chronostratigraphy constrains the burial and exhumation of the alcove containing the panel, and limits are also set by our related research dating both a rockfall that removed some figures and the rock’s exposure duration before that time. Results provide a maximum possible age, a minimum age, and an exposure time window for the creation of the Great Gallery panel, respectively. The only prior hypothesis not disproven is a late Archaic origin for BCS rock art, although our age result of A.D. ∼1–1100 coincides better with the transition to and rise of the subsequent Fremont culture. This chronology is for the type locality only, and variability in the age of other sites is likely. Nevertheless, results suggest that BCS rock art represents an artistic tradition that spanned cultures and the transition from foraging to farming in the region.Archaeology is focused upon material records, contextualized in time. Rock art is a record with the potential to provide unique insight into the dynamics and evolution of culture, but it generally lacks stratigraphic or chronologic context. Interpretation of the origin and meaning of rock art is indirect at best, or simply speculative. In the case of some pictographs, pigments may include or have enough accessory carbon for accelerator mass spectrometry (AMS) radiocarbon dating (1–4). In other special situations, such as caves, minimum age constraints have been obtained by various techniques of dating material that overlies or entombs rock art (5–7). However, most rock art remains undatable and researchers rely upon stylistic comparison and indirect associations with artifacts at nearby sites (8, 9). The case in point for this study is arguably the most compelling and debated rock art in the United States—the Barrier Canyon style (BCS) of the Colorado Plateau. Previous attempts to derive an absolute chronology have failed and its age remains unknown, with widely ranging hypotheses that have remained untested until now.The continued development of dating techniques offers new possibilities for hypothesis testing. The optically stimulated luminescence (OSL) signals from mineral grains make it possible to date the deposition of most sediment that is exposed to a few seconds of full sunlight before burial, and its use in the earth and cultural sciences has greatly increased (10, 11). Among the latest applications of OSL are techniques dating the outer surfaces of rock clasts that have become shielded from light, including those with archaeological context (12–15). Recent work has furthermore used the “bleaching” profile of decreasing luminescence signal toward the surface of rock to estimate exposure time to sunlight (16, 17). Using these dating tools, we can constrain the age of rock art and gain new insight into past cultures and landscapes.Here, we synthesize results from three approaches to dating the type section of BCS art, the Great Gallery in Canyonlands National Park of southeastern Utah. Through dating the full alluvial stratigraphy and a rockfall event that both have incontrovertible cross-cutting relations with the rock art, and then by determining the exposure duration of a painted rock surface, we greatly narrow the window of time when the rock art was created. These approaches do not require direct sampling of rock art and have strong potential for application to other archaeological and surface processes research. Although our results are only for the type section of BCS art, and chronological variability should be expected for the style across the region, they suggest that BCS art coincides with the transition to agriculture in the northern Colorado Plateau and may not have been limited to a specific archaeological culture.     

A 2014 update on the management of patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic, relapsing autoimmune connective tissue disease, primarily affecting the skin, joints, kidneys, heart, lungs, nervous system, blood elements, and serosal membranes. SLE is characterized by cytokine dysregulation, polyclonal B-cell activation, autoantibody production, and increased immune complex formation due to aberrations involving hyperactive B cells, T cells, and cells of the monocytic lineage. The symptoms of SLE are often diverse and nonspecific, and timely identification of SLE and associated comorbidities in patients is critical as aggressive monitoring and therapy may be warranted, especially in patients with poor prognoses. Based on the up-to-date understanding of the pathophysiology of SLE, the first targeted biological agent belimumab has been approved by the US Food and Drug Administration (FDA) in more than 50 years, and many targeted agents are being evaluated in late-stage clinical trials. There is a clear need to discuss how and when to incorporate new and emerging biological agents in managing patients with SLE. Additionally, the potential for increased risk of infections is a factor that heavily influences the rheumatologist?s decision to use biological agents in managing patients with SLE. Hence, in this roundtable educational activity, expert faculty will review and discuss the strategies for timely diagnosis of SLE and associated comorbidities. They will also discuss the current understanding of the pathophysiology of SLE and how new and emerging biological agents help address the underlying pathophysiological aberrations in patients with SLE. The faculty will also review strategies to minimize the risk of infections and other toxicities in patients with SLE.