Peter Drucker's ontology: understanding business relationships and networks

PURPOSE: The paper aims to consider the underlying premises of Peter Drucker’s managerial writing and focuses on three main aspects: humans and relations, an evolutionary perspective and a pragmatic perspective. These ontological views are taken to a new level and applied to explore the world of networked firms. DESIGN AND METHODOLOGY AND APPROACH: The paper is a conceptual contribution based on a literature study by the author. FINDINGS: An examination of Drucker’s ontology shows how his world perspective led him to an understanding of managers and organisations. The three elements of his ontology discussed are applied to research in business networks. RESEARCH LIMITATIONS AND IMPLICATIONS: The paper argues for research on human perspectives of business relationships and networks, particularly of issues such as time, timing, partner integration, relational and network embeddedness, network sensing, network horizons, and network identity. PRACTICAL IMPLICATIONS: Drucker’s ontological view enabled him to make pronouncements that cut through to the truth of reality in our organisationally shaped world. Understanding Drucker’s ontology provides managers with ways to deepen their understanding of an individual’s role at every level within an organisation. ORIGINALITY AND VALUE: The linking of Drucker’s ontology to research on new ways to organise and manage networked firms opens areas of future research.Christopher J. Medlinhttp://www.emeraldinsight.com/journals.htm?articleid=1704807

Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer's Disease Patients

BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer’s disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE ɛ4 allele carriers or noncarriers). METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE ɛ4 noncarriers and 1,121 carriers by independent neuroradiologists. Assessment of ARIA-E, ARIA-H, intracerebral hemorrhages, and age-related white matter changes is described. RESULTS: In the Final Read, treatment-emergent ARIA-E were identified in 242 patients including 76 additional cases not noted previously in real time. Overall, incidence proportion of ARIA-E was higher in carriers (active 21.2%; placebo 1.1%) than in noncarriers (pooled active 11.3%; placebo 0.6%), and was more often identified in homozygote APOE ɛ4 carriers than heterozygotes (34.5% versus 16.9%). Incidence rate of ARIA-E increased with increased dose in noncarriers. Frequency of ARIA-E first episodes was highest after the first and second bapineuzumab infusion and declined after repeated infusions. Incidence of total HDs <10 mm (cerebral microhemorrhages) was higher in active groups versus placebo. CONCLUSION: ARIA was detected more often on MRI scans when every scan was reviewed by trained neuroradiologists and results adjudicated. There was increased incidence of ARIA-E in bapineuzumab-treated carriers who had a microhemorrhage at baseline. ARIA-E was a risk factor for incident ARIA-H and late onset ARIA-E was milder radiologically. Age-related white matter changes did not progress during the study

Mutations in the Na+/K+-ATPase α3 Gene ATP1A3 Are Associated with Rapid-Onset Dystonia Parkinsonism

AbstractRapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability. We report the finding of six missense mutations in the gene for the Na+/K+-ATPase α3 subunit (ATP1A3) in seven unrelated families with RDP. Functional studies and structural analysis of the protein suggest that these mutations impair enzyme activity or stability. This finding implicates the Na+/K+ pump, a crucial protein responsible for the electrochemical gradient across the cell membrane, in dystonia and parkinsonism

Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings

Rapid-onset dystonia-parkinsonism (RDP) is a movement disorder associated with mutations in the ATP1A3 gene. Signs and symptoms of RDP commonly occur in adolescence or early adulthood and can be triggered by physical or psychological stress. Mutations in ATP1A3 are also associated with alternating hemiplegia of childhood (AHC). The neuropathologic substrate of these conditions is unknown. The central nervous system of four siblings, three affected by RDP and one asymptomatic, all carrying the I758S mutation in the ATP1A3 gene, was analyzed. This neuropathologic study is the first carried out in ATP1A3 mutation carriers, whether affected by RDP or AHC. Symptoms began in the third decade of life for two subjects and in the fifth for another. The present investigation aimed at identifying, in mutation carriers, anatomical areas potentially affected and contributing to RDP pathogenesis. Comorbid conditions, including cerebrovascular disease and Alzheimer disease, were evident in all subjects. We evaluated areas that may be relevant to RDP separately from those affected by the comorbid conditions. Anatomical areas identified as potential targets of I758S mutation were globus pallidus, subthalamic nucleus, red nucleus, inferior olivary nucleus, cerebellar Purkinje and granule cell layers, and dentate nucleus. Involvement of subcortical white matter tracts was also evident. Furthermore, in the spinal cord, a loss of dorsal column fibers was noted. This study has identified RDP-associated pathology in neuronal populations, which are part of complex motor and sensory loops. Their involvement would cause an interruption of cerebral and cerebellar connections which are essential for maintenance of motor control. Electronic supplementary material The online version of this article (doi:10.1007/s00401-014-1279-x) contains supplementary material, which is available to authorized users

The Assembled Genome of the Stroke-Prone Spontaneously Hypertensive Rat

BACKGROUND: We report the creation and evaluation of a de novo assembly of the genome of the spontaneously hypertensive rat, the most widely used model of human cardiovascular disease. METHODS: The genome is assembled from long read sequencing (PacBio HiFi and continuous long read data [CLR]) and scaffolded with long-range structural information obtained from Bionano optical maps and proximity ligation sequencing proximity analysis of the genome. The genome assembly was polished with Illumina short reads. Completeness of the assembly was investigated using Benchmarking Universal Single Copy Orthologs analysis. The genome assembly was also evaluated with the rat reference gene set, using NCBI automated protocols. We also generated orthogonal single molecule transcript sequence reads (Iso-Seq) from 8 tissues and used them to validate the coding assembly, to annotate the assembly with RNA transcripts representing unique full length transcript isoforms for each gene and to determine whether divergences between RefSeq sequences and the assembly were attributable to assembly errors or polymorphisms. RESULTS: The assembly analysis indicates that this assembly is comparable in contiguity and completeness to the current rat reference assembly, while the use of HiFi sequencing yields an assembly that is more correct at the single base level. Synteny analysis was performed to uncover the extent of synteny and the presence and distribution of chromosomal rearrangements between the reference and this assembly. CONCLUSION: The resulting genome assembly is reference quality and captures significant structural variation

A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1

A new mutant mouse (lamb1t) exhibits intermittent dystonic hindlimb movements and postures when awake, and hyperextension when asleep. Experiments showed co-contraction of opposing muscle groups, and indicated that symptoms depended on the interaction of brain and spinal cord. SNP mapping and exome sequencing identified the dominant causative mutation in the Lamb1 gene. Laminins are extracellular matrix proteins, widely expressed but also known to be important in synapse structure and plasticity. In accordance, awake recording in the cerebellum detected abnormal output from a circuit of two Lamb1-expressing neurons, Purkinje cells and their deep cerebellar nucleus targets, during abnormal postures. We propose that dystonia-like symptoms result from lapses in descending inhibition, exposing excess activity in intrinsic spinal circuits that coordinate muscles. The mouse is a new model for testing how dysfunction in the CNS causes specific abnormal movements and postures. DOI: http://dx.doi.org/10.7554/eLife.11102.00

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Study design and methods of the BoTULS trial: a randomised controlled trial to evaluate the clinical effect and cost effectiveness of treating upper limb spasticity due to stroke with botulinum toxin type A

Background Following a stroke, 55–75% of patients experience upper limb problems in the longer term. Upper limb spasticity may cause pain, deformity and reduced function, affecting mood and independence. Botulinum toxin is used increasingly to treat focal spasticity, but its impact on upper limb function after stroke is unclear. The aim of this study is to evaluate the clinical and cost effectiveness of botulinum toxin type A plus an upper limb therapy programme in the treatment of post stroke upper limb spasticity. Methods Trial design : A multi-centre open label parallel group randomised controlled trial and economic evaluation. Participants : Adults with upper limb spasticity at the shoulder, elbow, wrist or hand and reduced upper limb function due to stroke more than 1 month previously. Interventions : Botulinum toxin type A plus upper limb therapy (intervention group) or upper limb therapy alone (control group). Outcomes : Outcome assessments are undertaken at 1, 3 and 12 months. The primary outcome is upper limb function one month after study entry measured by the Action Research Arm Test (ARAT). Secondary outcomes include: spasticity (Modified Ashworth Scale); grip strength; dexterity (Nine Hole Peg Test); disability (Barthel Activities of Daily Living Index); quality of life (Stroke Impact Scale, Euroqol EQ-5D) and attainment of patient-selected goals (Canadian Occupational Performance Measure). Health and social services resource use, adverse events, use of other antispasticity treatments and patient views on the treatment will be compared. Participants are clinically reassessed at 3, 6 and 9 months to determine the need for repeat botulinum toxin type A and/or therapy. Randomisation : A web based central independent randomisation service. Blinding : Outcome assessments are undertaken by an assessor who is blinded to the randomisation group. Sample size : 332 participants provide 80% power to detect a 15% difference in treatment successes between intervention and control groups. Treatment success is defined as improvement of 3 points for those with a baseline ARAT of 0–3 and 6 points for those with ARAT of 4–56

Clinical utility of tibial motor and sensory nerve conduction studies with motor recording from the flexor hallucis brevis: a methodological and reliability study

<p>Abstract</p> <p>Background</p> <p>Standard tibial motor nerve conduction measures are established with recording from the abductor hallucis. This technique is often technically challenging and clinicians have difficulty interpreting the information particularly in the short segment needed to assess focal tibial nerve entrapment at the medial ankle as occurs in posterior tarsal tunnel syndrome. The flexor hallucis brevis (FHB) has been described as an alternative site for recording tibial nerve function in those with posterior tarsal tunnel syndrome. Normative data has not been established for this technique. This pilot study describes the technique in detail. In addition we provide reference values for medial and lateral plantar orthodromic sensory measures and assessed intrarater reliability for all measures.</p> <p>Methods</p> <p>Eighty healthy female participants took part, and 39 returned for serial testing at 4 time points. Mean values ± SD were recorded for nerve conduction measures, and coefficient of variation as well as intraclass correlation coefficients (ICC) were calculated.</p> <p>Results</p> <p>Motor latency, amplitude and velocity values for the FHB were 4.1 ± 0.9 msec, 8.0 ± 3.0 mV and 45.6 ± 3.4 m/s, respectively. Sensory latencies, amplitudes, and velocities, respectively, were 2.8 ± 0.3 msec, 26.7 ± 10.1 μV, and 41.4 ± 3.5 m/s for the medial plantar nerve and 3.2 ± 0.5 msec, 13.3 ± 4.7 μV, and 44.3 ± 4.0 msec for the lateral plantar nerve. All values demonstrated significant ICC values (<it>P </it>≤ 0.007).</p> <p>Conclusion</p> <p>Motor recording from the FHB provides technically clear waveforms that allow for an improved ability to assess tibial nerve function in the short segments used to assess tarsal tunnel syndrome. The reported means will begin to establish normal values for this technique.</p

Assessing the application of miscible CO2 flooding in oil reservoirs: a case study from Pakistan

Miscible carbon dioxide (CO2) flooding has been recognized as a promising approach to enhance the recovery of oil reservoirs. However, depending on the injection strategy and rock/fluid characteristics, efficiency of the miscible CO2flooding varies from reservoir to reservoir. Although, many studies have been carried out to evaluate the performance of the miscible CO2flooding, a specific strategy which can be strictly followed for a hydrocarbon reservoir has not been established yet. The aim of this study is to assess one of Pakistan’s oil reservoirs for miscible CO2flooding by applying a modified screening criterion and numerical modeling. As such, the most recent miscible CO2screening criteria were modified, and a numerical modeling was applied on the prospective reservoir. Based on the results obtained, South oil reservoir (S3) is chosen for a detailed assessment of miscible CO2flooding. It was also found that implementation of CO2water-alternating gas (CO2-WAG) injection at early stages of production can increase the production life of the reservoir