Are pathological lesions in neurodegenerative disorders the cause or the effect of the degeneration?

Pathological lesions in the form of extracellular protein deposits, intracellular inclusions and changes in cell morphology occur in the brain in the majority of neurodegenerative disorders. Studies of the presence, distribution, and molecular determinants of these lesions are often used to define individual disorders and to establish the mechanisms of lesion pathogenesis. In most disorders, however, the relationship between the appearance of a lesion and the underlying disease process is unclear. Two hypotheses are proposed which could explain this relationship: (i) lesions are the direct cause of the observed neurodegeneration ('causal' hypothesis); and (ii) lesions are a reaction to neurodegeneration ('reaction' hypothesis). These hypotheses are considered in relation to studies of the morphology and molecular determinants of lesions, the effects of gene mutations, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies and the degeneration of anatomical pathways. The balance of evidence suggests that in many disorders, the appearance of the pathological lesions is a reaction to degenerative processes rather than being their cause. Such a conclusion has implications both for the classification of neurodegenerative disorders and for studies of disease pathogenesis.

The East Asian crisis and financing corporate investment:is there a cause for concern?

In view of limited empirical evidence concerning the microeconomic aspects of corporate financial problems in the East Asian countries in the 1990s, this paper analyses the financing pattern of corporate investment in Indonesia, Korea, Malaysia, and Thailand. The analysis is based on an unbalanced panel of listed firms during the period 1989–1997. By using firm size, retention practices, and leverage as three different indicators of financial constraint on firm investment, we have examined the role of various internal and external financing variables on corporate investment in the sample countries. Results indicate that a large number of sample firms depend on free cash flow, especially in Indonesia; there was also a steady increase in debt-equity ratio in all countries. There were signs of agency costs in the use of cash flow in Korea and Malaysia and also in the use of debt financing in Malaysia and Thailand. There was also sign of over-investment among the Thai firms during 1994–1997 though it appears very little if at all was done to redress it in time.

Cause, effect and benefits of a standardised corporate visual identity system of UK companies operating in Malaysia

Investigates the degree of global standardisation of a corporate visual identity system (CVIS) in multinational operations. A special emphasis of this research is accorded to UK companies operating in Malaysia. In particular, the study seeks to reveal the reasons for developing a standardised CVIS; the behavioural issues associated with CVIS; and the determination in selecting a graphic design agency. The findings of the research revealed that multinational corporations in an increasingly corporate environment adopted a standardised CVIS for several reasons, including, aiding the sale of products and services, creating an attractive environment for hiring employees, and increasing the company’s stature and presence. Further findings show that the interest in global identity was stimulated by global restructuring, merger or acquisition. The above trends help explain why increased focus has been accorded to CVIS over the past five years by many UK companies operating in Malaysia. Additional findings reveal that both the UK design agencies and in-house design department are used in the development of the firms’ CVIS.

Issues of cause and control in patient accounts of Type 2 diabetes

Patients experience considerable difficulties in making and sustaining health-related lifestyle changes. Many Type 2 diabetes patients struggle to follow disease risk-management advice even when they receive extensive information and support. Drawing on a qualitative study of patients with Type 2 diabetes, the paper uses discourse analysis to examine their accounts about disease causation and disease management, and the implications for how they respond to their condition and health services advice. As it is a multifactorial disease, biomedical discourse around Type 2 diabetes is complex. Patients are encouraged to grasp the complicated message that both cause and medical outcomes related to their condition are partly, but not wholly, within their control. Discursive constructions identified from respondent accounts indicate how these two messages are deployed variously by respondents when accounting for disease causation and management. While these constructions (identified in respondent accounts as 'Up to me' and 'Down to them') are a valuable resource for patients, equally they may be deployed in a selective and detrimental way. We conclude that clear messages from health professionals about effective disease management may help patients to position themselves more effectively in relation to their condition. More importantly, they might serve to hinder the availability of inappropriate and potentially harmful patient positions where patients either relinquish responsibility for disease management or reject all input from health professionals. © The Author 2005. Published by Oxford University Press. All rights reserved.

Phonology as Cause, Symptom and Treatment? Early Reading Development and Dyslexia, by Valerie Muter, London: Whurr, 2003, 232 pages + viii, ISBN 1 86156 327 2

Book review

Is inflammation the cause of pre-eclampsia?

It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford-Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose-response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising.

Does FDI cause development? The ambiguity of the evidence and why it matters

The contribution that inward foreign direct investment (FDI) makes to development has been examined in a number of contexts including the relationship between inward FDI and new firm formation; growth; innovation, exports and competitiveness. However, no debate has proved so contentious, or so long lasting as that concerning the extent to which inward FDI stimulates productivity growth in the host country.

Controlling feeding practices:cause or consequence of early child weight?

INTRODUCTION. The exertion of control during child feeding has been associated with both underweight and overweight during childhood. What is as-yet unclear is whether controlling child feeding practices causally affect child weight or whether the use of control may be a reactive response to concerns about high or low child weight. The aims of this study were to explore the direction of causality in these relationships during infancy. METHODS. Sixty-two women gave informed consent to take part in this longitudinal study that spanned from birth to 2 years of child age. Mothers completed the Child Feeding Questionnaire at 1 year, and their children were weighed at 1 and 2 years of age. Child weight scores were converted into standardized z scores that accounted for child age and gender. RESULTS. Controlling for child weight at 1 year, the use of pressure to eat and restriction at 1 year significantly predicted lower child weight at 2 years. CONCLUSIONS. Controlling feeding practices in infancy have an impact on children's weight at 2 years. The use of restrictive child feeding practices during infancy predicts lower child weight at age 2 years, which may reinforce mothers' use of this strategy in the longer term despite its potential association with disinhibition and greater child weight in later childhood.

Toroidal flux oscillation as possible cause of geomagnetic excursions and reversals

It is proposed that convection driven dynamos operating in planetary cores could be oscillatory even when the oscillations are not directly noticeable from the outside. Examples of dynamo simulations are pointed out that exhibit oscillations in the structure of the azimuthally averaged toroidal magnetic flux while the mean poloidal field shows only variations in its amplitude. In the case of the geomagnetic field, global excursions may be associated with these oscillations. Long period dynamo simulations indicate that the oscillations may cause reversals once in a while. No special attempt has been made to use most realistic parameter values. Nevertheless some similarities between the simulations and the paleomagnetic record can be pointed out. Crown Copyright © 2008.

Fatty acid and phospholipid chlorohydrins cause cell stress and endothelial adhesion

The oxidation of low-density lipoprotein (LDL) is thought to contribute to atherogenesis, which is an inflammatory disease involving activation of phagocytic cells. Myeloperoxidase, an enzyme which is able to produce hypochlorous acid (HOCl), is released from these phagocytic cells, and has been found in an active form in atherosclerotic plaques. HOCl can oxidize both the lipid and protein moiety of LDL, and HOCl-modified LDL has been found to be pro-inflammatory, although it is not known which component is responsible for this effect. As HOCl can oxidize lipids to give chlorohydrins, we hypothesized that phospholipid chlorohydrins might have toxic and pro-inflammatory effects. We have formed chlorohydrins from fatty acids (oleic, linoleic and arachidonic acids) and from phospholipids (stearoyl-oleoyl phosphatidylcholine, stearoyl-linoleoyl phosphatidylcholine and stearoyl-arachidonoyl phosphatidylcholine), and investigated various biological effects of these oxidation products. Fatty acid and phospholipid chlorohydrins were found to deplete ATP levels in U937 cells in a concentration-dependent manner, with significant effects observed at concentrations of 25 µM and above. Low concentrations (25 µM) of stearoyl-oleoyl phosphatidylcholine and stearoyl-arachidonoyl phosphatidylcholine chlorohydrins were also found to increase caspase-3 activity. Finally, stearoyl-oleoyl phosphatidylcholine chlorohydrin increased leukocyte adhesion to artery segments isolated from C57Bl/6 mice. These results demonstrate potentially harmful effects of lipid chlorohydrins, and suggest that they may contribute to some of the pro-inflammatory effects that HOCl-modified low density lipoprotein has been found to induce.

Material and efficient cause interpretations of the formative model:resolving misunderstandings and clarifying conceptual language

This paper presents a causal explanation of formative variables that unpacks and clarifies the generally accepted idea that formative indicators are ‘causes’ of the focal formative variable. In doing this, we explore the recent paper by Diamantopoulos and Temme (AMS Review, 3(3), 160-171, 2013) and show that the latter misunderstand the stance of Lee, Cadogan, and Chamberlain (AMS Review, 3(1), 3-17, 2013; see also Cadogan, Lee, and Chamberlain, AMS Review, 3(1), 38-49, 2013). By drawing on the multiple ways that one can interpret the idea of causality within the MIMIC model, we then demonstrate how the continued defense of the MIMIC model as a tool to validate formative indicators and to identify formative variables in structural models is misguided. We also present unambiguous recommendations on how formative variables can be modelled in lieu of the formative MIMIC model.