What is the Value and Impact of Coaching at all Levels in the Organization?

[Excerpt] In the past coaching was nearly exclusively used for executive-level development, whereas coaching is currently approached as a more widespread intervention for various levels of employees within an organization. This application of coaching has developed over the past decade. The research on such coaching for talent management across the organization as it correlates to employee performance is fairly limited. Despite the limited research, several studies have shown that coaching to develop high potential employees (in addition to more traditional coaching aimed at executives) was successful, and yielded a return on investment. However, there are key factors that help define the best practices and added value of multi-level coaching within an organization

Laminar Flow Face Shield

The scope of this project was to design a personal protective equipment (PPE) that protects the wearer from SARS-CoV-2 without inhibiting communication and was comfortable to wear for long periods of time. SARS-CoV-2, commonly known as COVID-19, is a contagious respiratory virus that spreads through droplets produced when someone who is infected by the virus coughs, sneezes, or talks. These droplets may land on the mouths or noses of nearby people or may be inhaled in the lungs, infecting those who come in contact with the virus. The current guidelines to help slow the spread of COVID-19 are to wear a mask that covers the mouth and nose when around others [1]. However, this causes the wearer\u27s voice to be muffled and be difficult to understand, covers the wearer\u27s facial expressions, inhibits others from picking up on important facial cues, and can become uncomfortable after long periods of wear. An alternative that meets these needs would be a powered air-purifying respirator (PAPR), which is currently sold by several companies in various forms. Many are quite comfortable and allow the user’s face to be seen, but the price is the biggest downfall, most costing over $1,000. Our goal was to design a comfortable, affordable, and effective powered air purifying respirator for Cal Poly professors. We were able to create a respirator that costs only$140, filters out 99.93% of COVID-19 sized particles, and is generally well received in functionality by the general public. This document comprises the results of the critical design process, including background research, specifications, concept development and final design, testing and manufacturing plans, and project timeline

Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.

Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures

An Adaptive Perturbation-Based Heuristic: An Application to the Continuous p-Centre Problem

A self-adaptive heuristic that incorporates a variable level of perturbation, a novel local search and a learning mechanism is proposed to solve the p-centre problem in the continuous space. Empirical results, using several large TSP-Lib data sets, some with over 1300 customers with various values of p, show that our proposed heuristic is both effective and efficient. This perturbation metaheuristic compares favourably against the optimal method on small size instances. For larger instances the algorithm outperforms both a multi-start heuristic and a discrete-based optimal approach while performing well against a recent powerful VNS approach. This is a self-adaptive method that can easily be adopted to tackle other combinatorial/global optimisation problems. For benchmarking purposes, the medium size instances with nodes are solved optimally for the first time, though requiring a large amount of computational time. As a by-product of this research, we also report for the first time the optimal solution of the vertex p-centre problem for these TSP-Lib data sets

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries