A
bstract
We show that superpositions of classical states in quantum gravity with fixed topology can lead to new classical states with a different topology. We study this phenomenon in a particular ...limit of the LLM geometries. In this limit, the UV complete minisuperspace of allowed quantum states is exactly given by the Hilbert space of a free chiral boson in two dimensions. We construct this chiral boson purely in terms of combinatorial objects associated with the permutation group. As a byproduct of this analysis, we rederive the Murnaghan-Nakayama rule for characters of the permutation group. We are able to express this rule in terms of operator relations for raising and lowering operators on the Hilbert space of states in a free fermion basis. Our construction provides a preferred notion of bulk locality by studying an appropriate notion of D-brane state generating functions. We describe how multi-droplet LLM geometries with different topologies give new classical limits of the free chiral boson, even though they can be written as superpositions of coherent states with trivial topology. As a consequence, topology cannot be accessed by a single operator measurement in this quantum system. We study other non-linear measurements in the quantum wave-function, based on uncertainty and entanglement between modes of the chiral boson, that can be used as order parameters to measure the topology of such states.
Clinical myoelectric prostheses lack the sensory feedback and sufficient dexterity required to complete activities of daily living efficiently and accurately. Providing haptic feedback of relevant ...environmental cues to the user or imbuing the prosthesis with autonomous control authority have been separately shown to improve prosthesis utility. Few studies, however, have investigated the effect of combining these two approaches in a shared control paradigm, and none have evaluated such an approach from the perspective of neural efficiency (the relationship between task performance and mental effort measured directly from the brain). In this work, we analyzed the neural efficiency of 30 non-amputee participants in a grasp-and-lift task of a brittle object. Here, a myoelectric prosthesis featuring vibrotactile feedback of grip force and autonomous control of grasping was compared with a standard myoelectric prosthesis with and without vibrotactile feedback. As a measure of mental effort, we captured the prefrontal cortex activity changes using functional near infrared spectroscopy during the experiment. It was expected that the prosthesis with haptic shared control would improve both task performance and mental effort compared to the standard prosthesis. Results showed that only the haptic shared control system enabled users to achieve high neural efficiency, and that vibrotactile feedback was important for grasping with the appropriate grip force. These results indicate that the haptic shared control system synergistically combines the benefits of haptic feedback and autonomous controllers, and is well-poised to inform such hybrid advancements in myoelectric prosthesis technology.
OBJECTIVETo perform a retrospective analysis examining the incidence and prognosis of glioma patients with leptomeningeal disease (LMD) at Memorial Sloan Kettering Cancer Center over a 15-year period ...and correlate these findings with clinicopathologic characteristics.
METHODSWe conducted a retrospective review of glioma patients with LMD at Memorial Sloan Kettering Cancer Center diagnosed from 2001 to 2016. Patients were identified through a keyword search of their electronic medical record and by ICD-9 codes.
RESULTSOne hundred three patients were identified with disseminated LMD and 85 patients with subependymal spread of disease, 4.7% of all patients with glioma. These cohorts were analyzed separately for time to development of disseminated LMD/subependymal LMD, median overall survival, and survival from LMD diagnosis. Patients were pooled for subsequent analyses (n = 188) because of comparable clinical behavior. LMD was present at glioma diagnosis in 10% of patients. In the remaining 90% of patients diagnosed at recurrence, time to LMD diagnosis, survival after LMD diagnosis, and overall survival varied by original histology. Patients with oligodendroglioma had a median survival of 10.8 (range 1.8–67.7) months, astrocytoma 6.5 (0.1–28.5) months, and glioblastoma 3.8 (0.1–32.6) months after LMD diagnosis. In addition, we found that treatment of LMD was associated with superior performance status and increased survival.
CONCLUSIONPatients with LMD diagnosed at relapse may not have decreased overall survival as compared to historical controls with parenchymal relapse and may benefit from treatment.
Diffuse gliomas are the most common malignant brain tumours in adults and include glioblastomas and World Health Organization (WHO) grade II and grade III tumours (sometimes referred to as ...lower-grade gliomas). Genetic tumour profiling is used to classify disease and guide therapy
, but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease
. While the detection of circulating tumour DNA (ctDNA) in the blood of patients with primary brain tumours remains challenging
, sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost
. We therefore evaluated the representation of the glioma genome in CSF from 85 patients with gliomas who underwent a lumbar puncture because they showed neurological signs or symptoms. Here we show that tumour-derived DNA was detected in CSF from 42 out of 85 patients (49.4%) and was associated with disease burden and adverse outcome. The genomic landscape of glioma in the CSF included a broad spectrum of genetic alterations and closely resembled the genomes of tumour biopsies. Alterations that occur early during tumorigenesis, such as co-deletion of chromosome arms 1p and 19q (1p/19q codeletion) and mutations in the metabolic genes isocitrate dehydrogenase 1 (IDH1) or IDH2
, were shared in all matched ctDNA-positive CSF-tumour pairs, whereas growth factor receptor signalling pathways showed considerable evolution. The ability to monitor the evolution of the glioma genome through a minimally invasive technique could advance the clinical development and use of genotype-directed therapies for glioma, one of the most aggressive human cancers.
Temperature-dependent sex determination (TSD) was described nearly 50 years ago. Researchers have since identified many genes that display differential expression at male- vs. female-producing ...temperatures. Yet, it is unclear whether these genes (1) are involved in sex determination per se, (2) are downstream effectors involved in differentiation of ovaries and testes, or (3) are thermo-sensitive but unrelated to gonad development. Here we present multiple lines of evidence linking CIRBP to sex determination in the snapping turtle, Chelydra serpentina We demonstrate significant associations between a single nucleotide polymorphism (SNP) (c63A > C) in CIRBP, transcript levels in embryonic gonads during specification of gonad fate, and sex in hatchlings from a thermal regime that produces mixed sex ratios. The A allele was induced in embryos exposed to a female-producing temperature, while expression of the C allele did not differ between female- and male-producing temperatures. In accord with this pattern of temperature-dependent, allele-specific expression, AA homozygotes were more likely to develop ovaries than AC heterozygotes, which, in turn, were more likely to develop ovaries than CC homozygotes. Multiple regression using SNPs in CIRBP and adjacent loci suggests that c63A > C may be the causal variant or closely linked to it. Differences in CIRBP allele frequencies among turtles from northern Minnesota, southern Minnesota, and Texas reflect small and large-scale latitudinal differences in TSD pattern. Finally, analysis of CIRBP protein localization reveals that CIRBP is in a position to mediate temperature effects on the developing gonads. Together, these studies strongly suggest that CIRBP is involved in determining the fate of the bipotential gonad.
In the mammalian brain, perivascular astrocytes (PAs) closely juxtapose blood vessels and are postulated to have important roles in the control of vascular physiology, including regulation of the ...blood-brain barrier (BBB). Deciphering specific functions for PAs in BBB biology, however, has been limited by the ability to distinguish these cells from other astrocyte populations. In order to characterize selective roles for PAs
, a new mouse model has been generated in which the endogenous megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) gene drives expression of Cre fused to a mutated estrogen ligand-binding domain (Mlc1-T2A-CreERT2). This knock-in mouse model, which we term MLCT, allows for selective identification and tracking of PAs in the postnatal brain. We also demonstrate that MLCT-mediated ablation of PAs causes severe defects in BBB integrity, resulting in premature death. PA loss results in aberrant localization of Claudin 5 and -VE-Cadherin in endothelial cell junctions as well as robust microgliosis. Collectively, these data reveal essential functions for Mlc1-expressing PAs in regulating endothelial barrier integrity in mice and indicate that primary defects in astrocytes that cause BBB breakdown may contribute to human neurologic disorders.
Interlaced among the billions of neurons and glia in the mammalian brain is an elaborate network of blood vessels. Signals from the brain parenchyma control the unique permeability properties of cerebral blood vessels known as the blood-brain barrier (BBB). However, we understand very little about the relative contributions of different neural cell types in the regulation of BBB functions. Here, we show that a specific subpopulation of astrocyte is essential for control of BBB integrity, with ablation of these cells leading to defects in endothelial cell junctions, BBB breakdown, and resulting neurologic deficits.
The sustainability of rural groundwater supply infrastructure, primarily boreholes fitted with hand pumps, remains a challenge. This study evaluates whether coverage targets set out within the ...Millennium Development Goals (MDG) inadvertently increased the challenge to sustainably manage water supply infrastructure. Furthermore, the drive towards decentralised service delivery contributes to the financial burden of water supply assets. A sample size of 14,943 Afridev hand pump boreholes was extracted from a comprehensive live data set of 68,984 water points across Malawi to investigate the sustainability burden as emphasis shifts to the 2030 agenda. The results demonstrate that the push for coverage within the MDG era has impacted the sustainability of assets. A lack of proactive approaches towards major repairs and sub-standard borehole construction alongside aging infrastructure contributes to reduced functionality of decentralised supplies. Furthermore, costly rehabilitation is required to bring assets to operational standards, in which external support is commonly relied upon. Acceleration towards the coverage targets has contributed towards unsustainable infrastructure that has further implications moving forward. These findings support the need for Sustainable Development Goals (SDG) investment planning to move from a focus on coverage targets to a focus on quality infrastructure and proactive monitoring approaches to reduce the future burden placed on communities.
The self and eating disorders Bardone‐Cone, Anna M.; Thompson, Katherine A.; Miller, Alexandra J.
Journal of personality,
February 2020, 2020-02-00, 20200201, Letnik:
88, Številka:
1
Journal Article
Recenzirano
In our review, we focus on self‐related constructs in the context of eating disorders with four aims. First, we examine a variety of self‐related constructs that have been theoretically and ...empirically linked to the development and course of eating disorders. In addition to the more well‐researched constructs of self‐esteem and self‐efficacy, we also report on findings related to selflessness, contingent self‐worth, self‐objectification, ego‐syntonicity, self‐concept clarity, self‐compassion, social comparison, self‐oriented perfectionism/self‐criticism, and narcissism. Second, we discuss self‐related constructs that may be especially relevant to comorbidities common among those with eating disorders. Third, we review intervention and prevention programs where self‐related constructs play a prominent role. Lastly, we share future research directions regarding self‐related constructs and eating disorders that we believe will advance a deeper understanding of the role of the self in the eating disorders.
PDF
