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"Brooks, David"
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How to know a person : the art of seeing others deeply and being deeply seen
If you are going to care for someone, you must first understand them. If you're going to hire, marry, or befriend someone, you have to be able to see them. If you are going to work closely with someone, you have to be able to make them feel recognized and valued. As David Brooks observes, 'The older I get, the more I come to the certainty that there is one skill at the center of any healthy family, company, classroom, community or nation: the ability to see each other, to know other people, to make them feel valued, heard and understood.' And yet we humans don't do this well. All around us are people who feel invisible, unseen, misunderstood. In 'How to Know a Person', Brooks sets out to help us to do better, posing questions that are essential for all of us.
Book
The noradrenergic subtype of Parkinson disease: from animal models to clinical practice
Many advances in understanding the pathophysiology of Parkinson disease (PD) have been based on research addressing its motor symptoms and phenotypes. Various data-driven clinical phenotyping studies supported by neuropathological and in vivo neuroimaging data suggest the existence of distinct non-motor endophenotypes of PD even at diagnosis, a concept further strengthened by the predominantly non-motor spectrum of symptoms in prodromal PD. Preclinical and clinical studies support early dysfunction of noradrenergic transmission in both the CNS and peripheral nervous system circuits in patients with PD that results in a specific cluster of non-motor symptoms, including rapid eye movement sleep behaviour disorder, pain, anxiety and dysautonomia (particularly orthostatic hypotension and urinary dysfunction). Cluster analyses of large independent cohorts of patients with PD and phenotype-focused studies have confirmed the existence of a noradrenergic subtype of PD, which had been previously postulated but not fully characterized. This Review discusses the translational work that unravelled the clinical and neuropathological processes underpinning the noradrenergic PD subtype. Although some overlap with other PD subtypes is inevitable as the disease progresses, recognition of noradrenergic PD as a distinct early disease subtype represents an important advance towards the delivery of personalized medicine for patients with PD.Some patients with Parkinson disease (PD) present with mostly non-motor symptoms. Here, Chaudhuri et al. discuss the evidence for CNS abnormalities in noradrenergic function in these individuals. Recognition of this noradrenergic subtype of PD might ultimately lead to subtype-specific treatments and personalized medicine.
Journal Article
Imaging Approaches to Parkinson Disease
Parkinson disease (PD) is associated with nigral degeneration and striatal dopamine deficiency. Demonstrating midbrain structural abnormalities with transcranial sonography or diffusion-weighted MRI or showing striatal dopamine terminal dysfunction with PET or SPECT supports the diagnosis and rationalizes the use of dopaminergic medications. In atypical PD variants, transcranial sonography can detect striatal hyperechogenicity, and diffusion-weighted imaging can detect increased putamen water diffusion, whereas (18)F-FDG PET reveals reduced lentiform nucleus glucose metabolism. PET and SPECT can detect changes in striatal dopamine levels after levodopa administration and relate these to motor responses. Loss of cortical dopaminergic and cholinergic function is present in demented PD and, on occasion, amyloid deposits can be detected. Loss of cardiac sympathetic innervation can be sensitively detected in PD with (18)F-dopamine PET or (123)I-metaiodobenzylguanidine SPECT. Finally, PET can detect widespread brain inflammation in PD. This review discusses the role of structural and functional imaging for diagnosing and managing different parkinsonian syndromes.
Journal Article
New cold wars : China's rise, Russia's invasion, and America's struggle to defend the West
\"A fast-paced account of America's plunge into simultaneous Cold Wars against two very different adversaries-Xi Jinping's China and Vladimir Putin's Russia-based on deep reporting from inside the White House, U.S. intelligence agencies, technology firms, and foreign governments\"-- Provided by publisher.
Book
Neuroinflammation is independently associated with brain network dysfunction in Alzheimer’s disease
Brain network dysfunction is increasingly recognised in Alzheimer’s disease (AD). However, the causes of brain connectivity disruption are still poorly understood. Recently, neuroinflammation has been identified as an important factor in AD pathogenesis. Microglia participate in the construction and maintenance of healthy neuronal networks, but pro-inflammatory microglia can also damage these circuits. We hypothesised that microglial activation is independently associated with brain connectivity disruption in AD. We performed a cross-sectional multimodal imaging study and interrogated the relationship between imaging biomarkers of neuroinflammation, Aβ deposition, brain connectivity and cognition. 42 participants (12 Aβ-positive MCI, 14 Aβ-positive AD and 16 Aβ-negative healthy controls) were recruited. Participants had
11
C-PBR28 and
18
F-flutemetamol PET to quantify Aβ deposition and microglial activation, T1-weighted, diffusion tensor and resting-state functional MRI to assess structural network and functional network.
11
C-PBR28 uptake, structural network integrity and functional network orgnisation were compared across diagnostic groups and the relationship between neuroinflammation and brain network was tested in 26 Aβ-positive patients. Increased
11
C-PBR28 uptake, decreased FA, network small-worldness and local efficiency were observed in AD patients. Cortical
11
C-PBR28 uptake correlated negatively with structural integrity (standardised
β
= −0.375,
p
= 0.037) and network local efficiency (standardised
β
= −0.468,
p
< 0.001), independent of cortical thickness and Aβ deposition, while Aβ was not. Network structural integrity, small-worldness and local efficiency, and cortical thickness were positively associated with cognition. Our findings suggest cortical neuroinflammation coincide with structural and functional network disruption independent of Aβ and cortical atrophy. These findings link the brain connectivity change and pathological process in Alzheimer’s disease, and suggest a pathway from neuroinflammation to systemic brain dysfunction.
Journal Article
Rapid Detection of Mycobacterium tuberculosis by Recombinase Polymerase Amplification
Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39 °C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays could be of use for integration into a point-of-care test for use in resource constrained settings.
Journal Article
Full-Sun observations for identifying the source of the slow solar wind
Fast (>700 km s
−1
) and slow (~400 km s
−1
) winds stream from the Sun, permeate the heliosphere and influence the near-Earth environment. While the fast wind is known to emanate primarily from polar coronal holes, the source of the slow wind remains unknown. Here we identify possible sites of origin using a slow solar wind source map of the entire Sun, which we construct from specially designed, full-disk observations from the Hinode satellite, and a magnetic field model. Our map provides a full-Sun observation that combines three key ingredients for identifying the sources: velocity, plasma composition and magnetic topology and shows them as solar wind composition plasma outflowing on open magnetic field lines. The area coverage of the identified sources is large enough that the sum of their mass contributions can explain a significant fraction of the mass loss rate of the solar wind.
Both fast and slow solar winds emanate from our Sun, although the source of the slow component remains elusive. Towards identifying this, Brooks
et al
. present full-Sun spectral images from Hinode, combined with magnetic modelling, to produce a solar wind source map.
Journal Article