The quantification of business strategy

Подано групи показників, що описують кінцеві та проміжні результати реалізації стратегії та її окремих етапів і саму стратегію.The groups of indicators to describe the final and intermediate results of strategy and its separate stages implementation and the whole strategy are considered

ІНФОРМАЦІЙНО–АНАЛІТИЧНЕ ЗАБЕЗПЕЧЕННЯ ОЦІНЮВАННЯ В ЕКОНОМІЧНІЙ БЕЗПЕКОЛОГІЇ МІКРОРІВНЯ

One of the subject areas in economic security studies (a new direction in management science) is an assessment. Estimates of a particular object will most significantly reflect its state in case there is an information analytical support. Information analytical assessment provision in economic security studies must meet assessment information needs by providing such resource as indicators, using which it will be possible to have a high–quality economic security estimates of the objects selected for assessment. The indicators selection and further operations with them using the assessment methods to get the objects estimates in mіcrolevel economic security studies is performed taking into account an object of assessment, a research context of economic security, quality estimates requirements, availability and accessibility of information for determining values of indicators, estimates character (retrospective, current, predictive). There are some examples of indicators and methods of the objects assessment in the microlevel economic security studies considered that are eligible for assessment in a protective context of an enterprise economic security.Одной из предметных областей в науке об экономической безопасности (новое  направление в управленческой науке) является оценивание. Оценки конкретного объекта максимально достоверно будут отображать его состояние в случае наличия информационно–аналитического обеспечения. Информационно–аналитическое обеспечение оценивания в науке об экономической безопасности должно удовлетворять информационные потребности оценивания путем предоставления такого ресурса, как показатели, на основе которых можно получить качественные оценки экономической безопасности выбранных объектов оценивания. Выбор показателей и дальнейшие операции с ними с применением методов оценивания для получения оценок объектов в науке об экономической безопасности на микроуровне осуществляется с учетом объекта оценивания, контексты исследования экономической безопасности, требований к качеству оценок,  наличия и доступности информации для определения значений показателей, характера оценок (ретроспективные, текущие или прогнозные).  Как пример, представлено некоторые показатели и методы оценивания объектов в науке об экономической безопасности на микроуровне, которые подходят для оценивания в защитном контексте экономической безопасности предприятия.Однією з предметних областей в економічній безпекології (новий напрям в управлінській науці) є оцінювання. Оцінки конкретного об’єкта максимально достовірно будуть відображати його стан за наявності інформаційно–аналітичного забезпечення. Інформаційно–аналітичне забезпечення оцінювання в економічній безпекології має задовольнити інформаційні потреби оцінювання шляхом надання такого ресурсу як показники, з використанням яких можна отримати якісні оцінки економічної безпеки вибраних об’єктів оцінювання. Вибір показників та подальші операції з ними за допомогою методів оцінювання для отримання оцінок об’єктів в економічній безпекології макрорівня здійснюються з урахуванням об’єкта оцінювання, контексту дослідження економічної безпеки, вимог до якості оцінок, наявності та доступності інформації для визначення значень показників, характеру оцінок (ретроспективні, поточні, прогнозні). Як приклад надано деякі показники та методи оцінювання об’єктів в економічній безпекології мікрорівня, які придатні для оцінювання у захисному контексті економічної безпеки підприємства

The awareness assessment of “Ukrainian medical stomatological academy” students about methods of oral cavity care

Стабільно висока поширеність стоматологічних захворювань серед осіб різних вікових груп, значна ураженість каріозним процесом твердих тканин зубів та значна потреба у стоматологічній допомозі серед населення України - свідчать про необхідність удосконалення організації профілактики основних стоматологічних захворювань. Однією з актуальних проблем сучасної стоматології є недостатня інформованість населення про методи догляду за порожниною рота, хоча саме профілактика є вирішальною для запобігання виникненні захворювання. Наукова новизна. Вперше нами були досліджені показники поширеності та інтенсивності каріозного ураження серед студентів другого та третього курсів ВДНЗУ «УМСА» стоматологічного факультету та факультету підготовки іноземних студентів

Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease

Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking. We evaluated neuronal pentraxin 1 (NP1), a potential CNS-derived plasma biomarker of excitatory synaptic pathology. NP1 is preferentially expressed in brain and involved in glutamate receptor internalization. NP1 is secreted presynaptically induced by Aβ oligomers, and implicated in excitatory synaptic and mitochondrial deficits. Levels of NP1 and its fragments were increased in a correlated fashion in both brain and plasma of 7–8 month-old E4FAD mice relative to E3FAD mice. NP1 was also found in exosome preparations and reduced by dietary DHA supplementation. Plasma NP1 was higher in E4FAD+ (APOE4+/+/FAD+/−) relative to E4FAD- (non-carrier; APOE4+/+/FAD−/−) mice, suggesting NP1 is modulated by Aβ expression. Finally, relative to normal elderly, plasma NP1 was also elevated in patients with mild cognitive impairment (MCI) and elevated further in the subset who progressed to early-stage AD. In those patients, there was a trend towards increased NP1 levels in APOE4 carriers relative to non-carriers. These findings indicate that NP1 may represent a potential synapse-derived plasma biomarker relevant to early alterations in excitatory synapses in MCI and early-stage AD

Open-label add-on treatment trial of minocycline in fragile X syndrome

<p>Abstract</p> <p>Background</p> <p>Fragile X syndrome (FXS) is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP) leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9) in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in <it>fmr1 </it>knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS.</p> <p>Methods</p> <p>Twenty individuals with FXS, ages 13-32, were randomly assigned to receive 100 mg or 200 mg of minocycline daily. Behavioural evaluations were made prior to treatment (baseline) and again 8 weeks after daily minocycline treatment. The primary outcome measure was the Aberrant Behaviour Checklist-Community Edition (ABC-C) Irritability Subscale, and the secondary outcome measures were the other ABC-C subscales, clinical global improvement scale (CGI), and the visual analog scale for behaviour (VAS). Side effects were assessed using an adverse events checklist, a complete blood count (CBC), hepatic and renal function tests, and antinuclear antibody screen (ANA), done at baseline and at 8 weeks.</p> <p>Results</p> <p>The ABC-C Irritability Subscale scores showed significant improvement (p < 0.001), as did the VAS (p = 0.003) and the CGI (p < 0.001). The only significant treatment-related side effects were minor diarrhea (n = 3) and seroconversion to a positive ANA (n = 2).</p> <p>Conclusions</p> <p>Results from this study demonstrate that minocycline provides significant functional benefits to FXS patients and that it is well-tolerated. These findings are consistent with the <it>fmr1 </it>knockout mouse model results, suggesting that minocycline modifies underlying neural defects that account for behavioural abnormalities. A placebo-controlled trial of minocycline in FXS is warranted.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Open-Label Trial NCT00858689.</p

Nanoscale structure of amyloid-β plaques in Alzheimer’s disease

Abstract Soluble amyloid-β (Aβ) is considered to be a critical component in the pathogenesis of Alzheimer’s disease (AD). Evidence suggests that these non-fibrillar Aβ assemblies are implicated in synaptic dysfunction, neurodegeneration and cell death. However, characterization of these species comes mainly from studies in cellular or animal models, and there is little data in intact human samples due to the lack of adequate optical microscopic resolution to study these small structures. Here, to achieve super-resolution in all three dimensions, we applied Array Tomography (AT) and Stimulated Emission Depletion microscopy (STED), to characterize in postmortem human brain tissue non-fibrillar Aβ structures in amyloid plaques of cases with autosomal dominant and sporadic AD. Ultrathin sections scanned with super-resolution STED microscopy allowed the detection of small Aβ structures of the order of 100 nm. We reconstructed a whole human amyloid plaque and established that plaques are formed by a dense core of higher order Aβ species (~0.022 µm3) and a peripheral halo of smaller Aβ structures (~0.003 µm3). This work highlights the potential of AT-STED for human neuropathological studies

FMR1 premutation and full mutation molecular mechanisms related to autism

Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism

Targeted treatments for fragile X syndrome

Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet full criteria for ASD. Recent major advances have been made in the understanding of the neurobiology and functions of FMRP, the FMR1 (fragile X mental retardation 1) gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to the dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to the dysregulated translational pathway. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model at multiple stages of development. Clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess cognitive change that might be associated with treatment. Genes known to be causes of ASD interact with the translational pathway defective in FXS, and it has been hypothesized that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction between FXS and ASD. Therefore, targeted treatments developed for FXS may also target subgroups of ASD, and clinical trials in FXS may serve as a model for the development of clinical trial strategies for ASD and other cognitive disorders

Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients.

High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated patients. It is not known whether this is true in patients treated with second generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic CIP2A levels who receive a 2G TKI do not progress, unlike those treated with imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs. Patients with high CIP2A levels should be offered 2G TKI treatment in preference to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading to lower disease progression risk. The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome