Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural ...changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.
Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, ...surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m
) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.
1. Using a structured approach, participants will self-report the ability to understand the static and dynamic factors that influence treatment decision-making at diagnosis for children presenting ...with advanced cancer in LMICs.
2. Participants will reflect on the need to revise and develop treatment guidelines that are adaptable to resource-constrained settings and consider challenges faced by physicians caring for children presenting with advanced cancer at diagnosis, considering also the need to explore decision-making approaches of other key decision-partners.
Physicians face challenging treatment decision-making for children presenting with advanced cancer in LMICs. In this study, we sought to understand approaches to decision-making and factors modifying treatment recommendations at diagnosis. Preliminary findings describe how decision-making can be influenced by dynamic factors and cure-directed treatment is not always offered. Revision of treatment guidelines considering challenges faced in these contexts is required.
Physicians in low- and middle-income countries (LMICs) face challenging treatment decision-making for children presenting with advanced cancer. Decision-making in these circumstances has not been well described, and current treatment guidelines may not reflect challenges faced by physicians in LMICs.
In this study, we sought to understand physician decision-making approaches and factors that modify treatment recommendations at diagnosis for these children in LMICs.
Semi-structured interviews were conducted with physicians who treat children diagnosed with cancer across six World Health Organization (WHO) defined regions. Interviews were conducted using an online platform, audio-recorded, and transcribed. The research team developed a hybrid inductive/deductive codebook utilizing an existing framework describing factors influencing treatment decision-making and applied codes across transcripts. Thematic content analysis focused on decision-making approaches.
Thirty-six physicians completed interviews. Preliminary analysis describes decision-making processes with initial treatment recommendations based on static factors considered for all patients, including the diagnosis and disease burden. Many physicians described their inability to offer cure-directed treatment at diagnosis. Treatment recommendations were modified at two points: 1) prior to and 2) during or after the discussion with the patient/family. Dynamic factors that altered an initial recommendation included resource and treatment availability and allocation, treatment affordability, and family alignment or disagreement with the treatment recommendation.
Treatment decision-making for children presenting with advanced cancer in LMICs is not linear, and curative treatments cannot always be offered. Revision of treatment guidelines for use in resource-constrained settings which incorporate challenges faced and factors that modify decision-making in the context of advanced disease at diagnosis is required. Future work will explore the perspectives and decision-making approaches of patients/families to inform intervention design to support decision-making, including the provision of upfront non-curative treatment strategies and early integration of palliative care. This abstract was completed on behalf of the CATALYST Study Group.
Models of Palliative Care DeliveryGlobal Palliative Care
During development, biological neural networks produce more synapses and neurons than needed. Many of these synapses and neurons are later removed in a process known as neural pruning. Why networks ...should initially be over-populated, and the processes that determine which synapses and neurons are ultimately pruned, remains unclear. We study the mechanisms and significance of neural pruning in model neural networks. In a deep Boltzmann machine model of sensory encoding, we find that (1) synaptic pruning is necessary to learn efficient network architectures that retain computationally-relevant connections, (2) pruning by synaptic weight alone does not optimize network size and (3) pruning based on a locally-available measure of importance based on Fisher information allows the network to identify structurally important vs. unimportant connections and neurons. This locally-available measure of importance has a biological interpretation in terms of the correlations between presynaptic and postsynaptic neurons, and implies an efficient activity-driven pruning rule. Overall, we show how local activity-dependent synaptic pruning can solve the global problem of optimizing a network architecture. We relate these findings to biology as follows: (I) Synaptic over-production is necessary for activity-dependent connectivity optimization. (II) In networks that have more neurons than needed, cells compete for activity, and only the most important and selective neurons are retained. (III) Cells may also be pruned due to a loss of synapses on their axons. This occurs when the information they convey is not relevant to the target population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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