Board Effectiveness and Stock Liquidity Empirical Evidence at the Nairobi Securities Exchange

The aim of this paper was to assess the influence of the board effectiveness on the stock liquidity of firms listed at the Nairobi Securities Exchange. The success of security markets highly depends on stock liquidity. The ease of buying and selling of securities in the stock market while not bringing any effect on the prices. Board effectiveness has been found to play a key role as an aspect of corporate governance on firms’ financial performance but its role still remains unclear on stock liquidity of firms listed at the NSE. It is on this merit that this paper sought to fill the existing gap by establishing whether the board effectiveness influences stock liquidity of firms listed at the NSE. A census was carried out on all the 68 firms listed at the Nairobi securities exchange for the period spinning from 2014 to 2018. This study used secondary obtained from the NSE and the listed firms’ published annual financial reports. Data analysis was done using descriptive and inferential statistics. Under descriptive statistics; mean, median, minimum, maximum, and standard deviation were used and for the inferential statistics correlation and regression analysis within panel data framework were used. Data was subjected to diagnostic tests with Eviews 7 as the main statistical tool of analysis. The findings of the study indicated that board effectiveness had positive and significant influence on stock liquidity of firms listed at the NSE when quoted spread was used as measure but no significant influence when measured by turnover, illiquidity and liquidity ratio. This study recommended that more monitoring needs to be done to enable firms to reduce transaction cost. Key Words: Board Effectiveness, Stock Liquidity, Nairobi Securities Exchange. DOI: 10.7176/RJFA/12-10-12 Publication date:May 31st 202

Arteriolar neuropathology in cerebral microvascular disease

\ua9 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. Cerebral microvascular disease (MVD) is an important cause of vascular cognitive impairment. MVD is heterogeneous in aetiology, ranging from universal ageing to the sporadic (hypertension, sporadic cerebral amyloid angiopathy [CAA] and chronic kidney disease) and the genetic (e.g., familial CAA, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL] and cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy [CARASIL]). The brain parenchymal consequences of MVD predominantly consist of lacunar infarcts (lacunes), microinfarcts, white matter disease of ageing and microhaemorrhages. MVD is characterised by substantial arteriolar neuropathology involving ubiquitous vascular smooth muscle cell (SMC) abnormalities. Cerebral MVD is characterised by a wide variety of arteriolar injuries but only a limited number of parenchymal manifestations. We reason that the cerebral arteriole plays a dominant role in the pathogenesis of each type of MVD. Perturbations in signalling and function (i.e., changes in proliferation, apoptosis, phenotypic switch and migration of SMC) are prominent in the pathogenesis of cerebral MVD, making ‘cerebral angiomyopathy’ an appropriate term to describe the spectrum of pathologic abnormalities. The evidence suggests that the cerebral arteriole acts as both source and mediator of parenchymal injury in MVD

Supporting Mitosis Detection AI Training with Inter-Observer Eye-Gaze Consistencies

The expansion of artificial intelligence (AI) in pathology tasks has intensified the demand for doctors' annotations in AI development. However, collecting high-quality annotations from doctors is costly and time-consuming, creating a bottleneck in AI progress. This study investigates eye-tracking as a cost-effective technology to collect doctors' behavioral data for AI training with a focus on the pathology task of mitosis detection. One major challenge in using eye-gaze data is the low signal-to-noise ratio, which hinders the extraction of meaningful information. We tackled this by levering the properties of inter-observer eye-gaze consistencies and creating eye-gaze labels from consistent eye-fixations shared by a group of observers. Our study involved 14 non-medical participants, from whom we collected eye-gaze data and generated eye-gaze labels based on varying group sizes. We assessed the efficacy of such eye-gaze labels by training Convolutional Neural Networks (CNNs) and comparing their performance to those trained with ground truth annotations and a heuristic-based baseline. Results indicated that CNNs trained with our eye-gaze labels closely followed the performance of ground-truth-based CNNs, and significantly outperformed the baseline. Although primarily focused on mitosis, we envision that insights from this study can be generalized to other medical imaging tasks.Comment: Accepted by IEEE International Conference on Healthcare Informatics 202

Neuropathology of trisomy 21 mosaicism in a case with early-onset dementia.

INTRODUCTION: This study investigated the impact of trisomy 21 mosaicism (mT21) on Alzheimers disease (AD) neuropathology in a well-characterized clinical case described by Ringman et al. METHODS: We describe AD neuropathology in mT21 including amyloid beta, phosphorylated tau, astrogliosis, microgliosis, α-synuclein, and TAR DNA-binding protein 43 (TDP-43) in cerebral cortex, hippocampal subregions, and amygdala using immunohistochemistry. RESULTS: We observed high AD neuropathologic change with a score of A3B3C3. In addition, there was widespread astrogliosis, cerebral amyloid angiopathy, and perivascular space widening throughout the brain. Lewy bodies and neurites were noted in the amygdala only and no TDP-43 was observed. DISCUSSION: The findings in this case report highlight that mT21 is sufficient to induce AD neuropathology and early-onset dementia. HIGHLIGHTS: Trisomy 21 mosaicism (mT21) occurs when three copies of chromosome 21 are present in some but not all somatic cells in an individual. mT21 accounts for ≈ 2% of people diagnosed with Down syndrome (DS). Immunohistochemical identification of amyloid beta, tau, astrocytes, microglia, α-synuclein, and TAR DNA-binding protein 43 show that Alzheimers disease (AD) pathology in mT21 is similar to full trisomy 21. The findings in this case report highlight that mT21 is sufficient to induce AD neuropathology and early-onset dementia

Augmenting Pathologists with NaviPath: Design and Evaluation of a Human-AI Collaborative Navigation System

Artificial Intelligence (AI) brings advancements to support pathologists in navigating high-resolution tumor images to search for pathology patterns of interest. However, existing AI-assisted tools have not realized this promised potential due to a lack of insight into pathology and HCI considerations for pathologists' navigation workflows in practice. We first conducted a formative study with six medical professionals in pathology to capture their navigation strategies. By incorporating our observations along with the pathologists' domain knowledge, we designed NaviPath -- a human-AI collaborative navigation system. An evaluation study with 15 medical professionals in pathology indicated that: (i) compared to the manual navigation, participants saw more than twice the number of pathological patterns in unit time with NaviPath, and (ii) participants achieved higher precision and recall against the AI and the manual navigation on average. Further qualitative analysis revealed that navigation was more consistent with NaviPath, which can improve the overall examination quality.Comment: Accepted ACM CHI Conference on Human Factors in Computing Systems (CHI '23

Monoaminergic neurotransmitters are bimodal effectors of tau aggregation.

Neurotransmitters (NTs) mediate trans-synaptic signaling, and disturbances in their levels are linked to aging and brain disorders. Here, we ascribe an additional function for NTs in mediating intracellular protein aggregation by interaction with cytosolic protein fibrils. Cell-based seeding experiments revealed monoaminergic NTs as inhibitors of tau. Seeding is a disease-relevant mechanism involving catalysis by fibrils, leading to the aggregation of proteins in Alzheimers disease and other neurodegenerative diseases. Chemotyping small molecules with varied backbone structures revealed determinants of aggregation inhibitors and catalysts. Among those identified were monoaminergic NTs. Dose titrations revealed bimodal effects indicative of fibril disaggregation, with aggregation catalysis occurring at low ratios of NTs and inhibited seeding ensuing at higher concentrations. Bimodal effects by NTs extend from in vitro systems to dopaminergic neurons, suggesting that pharmacotherapies that modify intracellular NT levels could shape the neuronal protein aggregation environment

A Case of Holocord Leptomeningeal Dissemination from Cerebellar Hemangioblastoma without von Hippel-Lindau Disease

Hemangioblastoma disseminated along leptomeninges from the solitary cranial lesion without von Hippel-Lindau (VHL) disease is a quite rare instance with 23 cases reported in 40 years. We add a new case and discuss these rare instances. A 55-year-old female underwent surgery for total removal of cerebellar hemangioblastoma. Twenty months later, magnetic resonance (MR) images of the spinal cord revealed a tumor compressing the thoracic cord at T3-4 level which was removed en bloc by emergent spinal surgery. However, paraplegia and bowel bladder dysfunction recurred 5 months after the spinal surgery. Spine MR images showed diffuse enhancement of subarachnoid space. Exploratory surgery disclosed that the enhanced lesion was disseminated hemangioblastoma. After whole spinal irradiation, she was transferred to a palliative care hospital. Even after complete removal, possibility of leptomeningeal dissemination demands continuous follow-up. The mechanism of seeding of hemangioblastoma remains unclear, but attention must be paid to avoid spreading tumor cells during surgery because all the disseminated cases had precedent cranial surgery

xPath: Human-AI Diagnosis in Pathology with Multi-Criteria Analyses and Explanation by Hierarchically Traceable Evidence

Data-driven AI promises support for pathologists to discover sparse tumor patterns in high-resolution histological images. However, from a pathologist's point of view, existing AI suffers from three limitations: (i) a lack of comprehensiveness where most AI algorithms only rely on a single criterion; (ii) a lack of explainability where AI models tend to work as 'black boxes' with little transparency; and (iii) a lack of integrability where it is unclear how AI can become part of pathologists' existing workflow. Based on a formative study with pathologists, we propose two designs for a human-AI collaborative tool: (i) presenting joint analyses of multiple criteria at the top level while (ii) revealing hierarchically traceable evidence on-demand to explain each criterion. We instantiate such designs in xPath -- a brain tumor grading tool where a pathologist can follow a top-down workflow to oversee AI's findings. We conducted a technical evaluation and work sessions with twelve medical professionals in pathology across three medical centers. We report quantitative and qualitative feedback, discuss recurring themes on how our participants interacted with xPath, and provide initial insights for future physician-AI collaborative tools.Comment: 31 pages, 11 figure

Brain-wide alterations revealed by spatial transcriptomics and proteomics in COVID-19 infection.

Understanding the pathophysiology of neurological symptoms observed after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is essential to optimizing outcomes and therapeutics. To date, small sample sizes and narrow molecular profiling have limited the generalizability of findings. In this study, we profiled multiple cortical and subcortical regions in postmortem brains of patients with coronavirus disease 2019 (COVID-19) and controls with matched pulmonary pathology (total n = 42) using spatial transcriptomics, bulk gene expression and proteomics. We observed a multi-regional antiviral response without direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and upregulation of neuroinflammation in glia, consistent across both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in age-related neurodegenerative diseases, including Parkinsons disease and Alzheimers disease. Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe acute/subacute COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging and neurodegeneration

Neuropathology of COVID-19 (neuro-COVID): clinicopathological update

Coronavirus disease 2019 (COVID-19) is emerging as the greatest public health crisis in the early 21st century. Its causative agent, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is an enveloped single-stranded positive-sense ribonucleic acid virus that enters cells via the angiotensin converting enzyme 2 receptor or several other receptors. While COVID-19 primarily affects the respiratory system, other organs including the brain can be involved. In Western clinical studies, relatively mild neurological dysfunction such as anosmia and dysgeusia is frequent (~70-84%) while severe neurologic disorders such as stroke (~1-6%) and meningoencephalitis are less common. It is unclear how much SARS-CoV-2 infection contributes to the incidence of stroke given co-morbidities in the affected patient population. Rarely, clinically-defined cases of acute disseminated encephalomyelitis, Guillain-Barré syndrome and acute necrotizing encephalopathy have been reported in COVID-19 patients. Common neuropathological findings in the 184 patients reviewed include microglial activation (42.9%) with microglial nodules in a subset (33.3%), lymphoid inflammation (37.5%), acute hypoxic-ischemic changes (29.9%), astrogliosis (27.7%), acute/subacute brain infarcts (21.2%), spontaneous hemorrhage (15.8%), and microthrombi (15.2%). In our institutional cases, we also note occasional anterior pituitary infarcts. COVID-19 coagulopathy, sepsis, and acute respiratory distress likely contribute to a number of these findings. When present, central nervous system lymphoid inflammation is often minimal to mild, is detected best by immunohistochemistry and, in one study, indistinguishable from control sepsis cases. Some cases evince microglial nodules or neuronophagy, strongly supporting viral meningoencephalitis, with a proclivity for involvement of the medulla oblongata. The virus is detectable by reverse transcriptase polymerase chain reaction, immunohistochemistry, or electron microscopy in human cerebrum, cerebellum, cranial nerves, olfactory bulb, as well as in the olfactory epithelium; neurons and endothelium can also be infected. Review of the extant cases has limitations including selection bias and limited clinical information in some cases. Much remains to be learned about the effects of direct viral infection of brain cells and whether SARS-CoV-2 persists long-term contributing to chronic symptomatology