Alliance boots’ leveraged buyout: is KKR a true barbarian at the gate?

This case study discusses the leveraged buyout (LBO) of Alliance Boots, a multinational company operating in the pharmaceutical, health and beauty industry. The case is particularly focused in the investing part of the private equity cycle and, more specifically, on the motivations for a LBO, on private equity returns and on the relationship between pricing under a competitive bidding process and limited partners' returns. In March 2007, a consortium composed by KKR and Stefano Pessina intended to buy Alliance Boots, however there was another bidder who also wanted to acquire the firm. In face of this competitive market situation, KKR and Pessina had to decide whether to increase the offer price to acquire the firm, while guaranteeing good future returns

Deficiencies in one-carbon metabolism led to increased neurological disease risk and worse outcome: homocysteine is a marker of disease state

Elevated plasma homocysteine levels have been identified as a significant, independent risk factor for the development of cognitive decline including Alzheimer’s disease. While several studies have explored the link between homocysteine and disease risk, the associations have not been entirely clear. Elevated levels of homocysteine serve as a disease marker and understanding the underlying cause of these increased levels (e.g., dietary or genetic deficiency in one-carbon metabolism, 1C) will provide valuable insights into neurological disease risk and outcomes. Previous cell culture experiments investigating the mechanisms involved used ultra-high levels of homocysteine that are not observed in human patients. These studies have demonstrated the negative impacts of ultra-high levels of homocysteine can have on for example proliferation of neuroprogenitor cells in the adult hippocampus, as well as triggering neuronal apoptosis through a series of events, including DNA damage, PARP activation, NAD depletion, mitochondrial dysfunction, and oxidative stress. The aim of this mini-review article will summarize the literature on deficiencies in 1C and how they contribute to disease risk and outcomes and that homocysteine is a marker of disease

Reduced brain volume and impaired memory in betaine homocysteine S -methyltransferase knockout mice

Using a mouse model, this study examined the impact of lack of betaine homocysteine S-methyltransferase (BHMT) on neurological function. Bhmt-/- mice maintained on a control diet had elevated concentrations of homocysteine, reduced total brain MRI volume, as well as impaired reference and short- term memories. The results of this study indicate that the absence of BHMT may play a role in neurological function

Increased homocysteine levels impair reference memory and reducecortical levels of acetylcholine in a mouse model of vascular cognitive impairment

Folates are B-vitamins that are vital for normal brain function. Deficiencies in folates either genetic(methylenetetrahydrofolate reductase, MTHFR) or dietary intake of folic acid result in elevated levelsof homocysteine. Clinical studies have shown that elevated levels of homocysteine (Hcy) may be associ-ated with the development of dementia, however this link remains unclear. The purpose of this study wasto evaluate the impact of increased Hcy levels on a mouse model of vascular cognitive impairment (VCI)produced by chronic hypoperfusion. Male and female Mthfr+/+and Mthfr+/−mice were placed on eithercontrol (CD) or folic acid deficient (FADD) diets after which all animals underwent microcoil implantationaround each common carotid artery or a sham procedure. Post-operatively animals were tested on theMorris water maze (MWM), y-maze, and rotarod. Animals had no motor impairments on the rotarod,y-maze, and could learn the location of the platform on the MWM. However, on day 8 of testing of MWMtesting during the probe trial, Mthfr+/−FADD microcoil mice spent significantly less time in the targetquadrant when compared to Mthfr+/−CD sham mice, suggesting impaired reference memory. All FADDmice had elevated levels of plasma homocysteine. MRI analysis revealed arterial remodeling was present in Mthfr+/− microcoil mice not Mthfr+/+ mice. Acetylcholine and related metabolites were reduced in cortical tissue because of microcoil implantation and elevated levels of homocysteine. Deficiencies in folate metabolism resulting in increased Hcy levels yield a metabolic profile that increases susceptibility to neurodegeneration in a mouse model of VCI

Studies on Sheet Explosive Formulation Based on Octahydro-1,3,5,7-Tetranitro-1,3,5,7-Tetrazocine and Hydroxyl Terminated Polybutadiene

The effect of replacing hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in HTPB-binder on the performance, sensitivity, thermal, and mechanical properties of the sheet explosive formulation has been studied. The maximum loading of HMX was achieved up to 78 per cent in HTPB-binder system. The velocity of detonation (VOD) of HMX-based sheet explosive was observed about 7300 m/s which is marginally higher than existing RDX-based sheet explosive formulation (RDX/HTPB-binder, 80/20). The VOD trends were verified by theoretical calculation by BKW code using FORTRAN executable program. The thermal decomposition kinetics of sheet explosive formulations was investigated by differential scanning calorimetry. The activation energy for sheet explosive formulation HMX/HTPB-binder (78/22) was calculated using Kissinger kinetic method and found to be 170.08 kJ/mol, infer that sheet explosive formulation is thermally stable

Nutritional Influences on the Health of Women and Children in Cabo Delgado, Mozambique: A Qualitative Study

In 2017, the Government of Mozambique declared localized acute malnutrition crises in a range of districts across Mozambique including Cabo Delgado. This is in spite of intensive efforts by different non-governmental organizations (NGO) and the Government of Mozambique to expand access to information on good nutritional practices as well as promote nutrition-specific interventions, such as cooking demonstrations, home gardens and the distribution of micronutrient powder to children. This paper examines and discusses key nutritional influences on the health of pregnant and breastfeeding mothers in Cabo Delgado province, Mozambique. We conducted 21 key informant interviews (KIIs) with a wide range of stakeholders and 16 in-depth interviews (IDIs) with women. In addition, we conducted four focus group discussions with each of the following groups: (1) pregnant adolescent girls, (2) pregnant women \u3e20 yrs, (3) women \u3e20 yrs with babies \u3c6 mths who were not practicing exclusive breastfeeding, (4) women \u3e20 yrs of children \u3c2 yrs and (5) with fathers of children \u3c2 yrs. Data were analyzed thematically using NVIVO software. There is no single widely held influence on pregnant and breast-feeding women’s nutritional decision-making, choices and food consumption. Rather, variables such as social-cultural, environmental, economic, gender, knowledge and information intersect in their roles in nutritional food choice

Interactions of stress and motor system function

ix, 128 leaves : ill. (some col.) ; 29 cm.Stress is one of the most critical influences on behavior, performance and disease. Recent findings from our laboratory have shown that stress represents a major modulator of motor function in the intact and damaged brain. The mechanisms by which stress and stress hormones affect motor system function, however, have not yet been determined. The objective of this thesis was to determine the route of action of stress and stress hormones on the motor system in a rat model. The first experiment investigates whether corticosterone is involved in mediating stress-induced motor impairments. The second experiment compares the role of glucocorticoid and mineralocorticoid receptors in regard to modulating the motor response to stress. The third experiment determines the differential effects of stress on motor function in males and females. The final experiment systematically describes changes in neuronal cell signaling that affect normal function of motor areas. The results indicate that disturbance of fine motor control by stress is not associated with stress hormone increases. Furthermore, it is modulated through the glucocorticoid and mineralocorticoid receptors. Stress differentially impairs motor function in males and females. These changes in motor behaviour could possibly be the result of changes in neuronal cell signaling within the motor system. This research provides new insights into physiological influences in motor system function and disorders of the motor system

Elevated levels of plasma homocysteine, deficiencies in dietary folic acid and uracil–DNA glycosylase impair learning in a mouse model of vascular cognitive impairment

Dietary deficiencies in folic acid result in elevated levels of plasma homocysteine, which has been associated with the development of dementia and other neurodegenerative disorders. Previously, we have shown that elevated levels of plasma homocysteine in mice deficient for a DNA repair enzyme, uracil–DNA glycosylase (UNG), result in neurodegeneration. The goal of this study was to evaluate how deficiencies in folic acid and UNG along with elevated levels of homocysteine affect vascular cognitive impairment, via chronic hypoperfusion in an animal model. Ung+/+ and Ung−/− mice were placed on either control (CD) or folic acid deficient (FADD) diets. Six weeks later, the mice either underwent implantation of microcoils around both common carotid arteries. Post-operatively, behavioral tests began at 3-weeks, angiography was measured after 5-weeks using MRI to assess vasculature and at completion of study plasma and brain tissue was collected for analysis. Learning impairments in the Morris water maze (MWM) were observed only in hypoperfused Ung−/− FADD mice and these mice had significantly higher plasma homocysteine concentrations. Interestingly, Ung+/+ FADD produced significant remodeling of the basilar artery and arterial vasculature. Increased expression of GFAP was observed in the dentate gyrus of Ung−/− hypoperfused and FADD sham mice. Chronic hypoperfusion resulted in increased cortical MMP-9 protein levels of FADD hypoperfused mice regardless of genotypes. These results suggest that elevated levels of homocysteine only, as a result of dietary folic acid deficiency, don’t lead to memory impairments and neurobiochemical changes. Rather a combination of either chronic hypoperfusion or UNG deficiency is required

A survey-based analysis of the academic job market

Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success - including funding, number of publications or journals published in - were unable to completely differentiate applicants with and without job offers. Respondents also reported that the hiring process was unnecessarily stressful, time-consuming, and lacking in feedback, irrespective of outcome. Our findings suggest that there is considerable scope to improve the transparency of the hiring process