This paper considers some of the theoretical and practical problems of conducting cost-utility analyses alongside clinical trials. In order to measure utilities of different health states in a clinical trial a number of critical assumptions have to be made. Some of these assumptions are questionable on a theoretical level, others empirically invalid. The practical problems of measuring utilities are discussed. The standard gamble is shown to be the most validated method of utility measurement, but still based on very strong assumptions. The standard gamble instrument is also costly and difficult to administer in clinical trials. Other instruments are found to be less valid than the standard gamble. It is concluded that although cost-utility analysis seems relevant in some instances, investigators should avoid this assessment of utility and instead measure cost-effectiveness, cost-benefit and quality of life.

In order to utilise the position and attitude information of a Celestial Navigation System (CNS) to aid a Strapdown Inertial Navigation System (SINS) and make it possible to achieve long-range and high-precision navigation, a new SINS/CNS integrated navigation scheme based on overall optimal correction is proposed. Firstly, the optimal installation angle of the star sensor is acquired according to the geometric relationship between the refraction stars area and the star sensor's visual field. Secondly, an analytical method to determine position and horizontal reference is introduced. Thirdly, the mathematical model of the SINS/CNS integrated navigation system is established. Finally, some simulations are carried out to compare the navigation performance of the proposed SINS/CNS integrated scheme with that of the traditional gyro-drift-corrected integration scheme. Simulation results indicate that in the proposed scheme, without the aid of SINS, CNS can provide attitude and position information and the errors of the SINS are able to be estimated and corrected efficiently. Therefore, the navigation performance of the proposed SINS/CNS scheme is superior to that of a more traditional scheme in long-range flight.

Traumatic brain injury (TBI) results in a variable degree of cerebral atrophy that is not always related to cognitive measures across studies. However, the use of different methods for examining atrophy may be a reason why differences exist. The purpose of this manuscript was to examine the predictive utility of seven magnetic resonance imaging (MRI) -derived brain volume or indices of atrophy for a large cohort of TBI patients (n = 65). The seven quantitative MRI (qMRI) measures included uncorrected whole brain volume, brain volume corrected by total intracranial volume, brain volume corrected by the ratio of the individual TICV by group TICV, a ventricle to brain ratio, total ventricular volume, ventricular volume corrected by TICV, and a direct measure of parenchymal volume loss. Results demonstrated that the various qMRI measures were highly interrelated and that corrected measures proved to be the most robust measures related to neuropsychological performance. Similar to an earlier study that examined cerebral atrophy in aging and dementia, these results suggest that a single corrected brain volume measure is all that is necessary in studies examining global MRI indicators of cerebral atrophy in relationship to cognitive function making additional measures of global atrophy redundant and unnecessary. (JINS, 2011, 17, 308–316)

Neurological involvement following trypanosome infection has been recognised for over a century. However, there are still many unanswered questions concerning the mechanisms used by the parasite to gain entry to the CNS and the pathogenesis of the resulting neuroinflammatory reaction. There is a paucity of material from human cases of the disease therefore the majority of current research relies on the use of animal models of trypanosome infection. This review reports contemporary knowledge, from both animal models and human samples, regarding parasite invasion of the CNS and the neuropathological changes that accompany trypanosome infection and disease progression. The effects of trypanosomes on the blood-brain barrier are discussed and possible key molecules in parasite penetration of the barrier highlighted. Changes in the balance of CNS cytokines and chemokines are also described. The article closes by summarising the effects of trypanosome infection on the circadian sleep-wake cycle, and sleep structure, in relation to neuroinflammation and parasite location within the CNS. Although a great deal of progress has been made in recent years, the advent and application of sophisticated analysis techniques, to decipher the complexities of HAT pathogenesis, herald an exciting and rewarding period for advances in trypanosome research.

The anti-psychotic drug management of patients with schizophrenia and HIV-1 infection is problematic. Such individuals are prone to extra-pyramidal reactions on account of HIV-1 induced sub-cortical involvement and exacerbation of cognitive impairment due to underlying CNS infection. Compliance with treatment can be problematic due to a disordered mental state and bone marrow toxicity may also result from the combined effects of anti-psychotic and retroviral agents. It is generally thought that atypical anti-psychotic drugs are the treatment of choice in such cases.

We present the case of a 30-year-old man with a history of schizophrenia who was successfully treated with clozapine following an admission to a psychiatric unit with acute confusional symptoms secondary to HIV-related central nervous system (CNS) involvement.

In this in vitro study we investigated whether previously described in vivo plasma-associated effects, that occurred in the period shortly after penetration of Trichobilharzia ocellata into the snail host Lymnaea stagnalis (1.5–72 h post-exposure; p.e.) were direct and/or indirect effects of parasite-derived factor(s). It was investigated whether the effect is mediated by the central nervous system (CNS) of the host. Phagocytic activity of the haemocytes was taken as a parameter for the activity of internal defence of the host. A number of preliminary experiments were performed. When the supernatant of in vitro cultured parasites (33 h; corresponding with their developmental stage in vivo when plasma-associated activation was found) was applied directly to monolayers of haemocytes, it appeared to enhance their phagocytic activity. No direct effect, however, was found with a supernatant of parasites cultured for a longer period of time (72 h; when, in vivo, a plasma-associated suppression was found). In this case, indirect suppression was detected: the parasites appeared to have released a factor that induced the CNS of the host to release material suppressing the activity of the internal defence system of the host. To date the nature of this factor is unknown.

Attentional impairments in children occur in the context of both developmental and acquired disorders involving the central nervous system (CNS) and may have implications for ongoing development, potentially impeding cognitive, educational, and behavioral functions. Using a continuous performance paradigm (CPT), this study compared attentional profiles of children with developmental and acquired conditions impacting on the CNS: (i) attention deficit–hyperactivity disorder (ADHD: n = 27); (ii) moderate traumatic brain injury (TBI: n = 41); (iii) acute lymphoblastic leukemia (n = 31); and (iv) insulin-dependent diabetes mellitus (n = 39). A healthy control group (n = 46) was also examined. Groups were compared on measures of sustained attention, selective attention, and response inhibition. In addition, measures of performance variability and deterioration and processing speed were examined. Results showed that children with ADHD exhibited global and severe attentional impairments in contrast to all other groups. Children with moderate TBI displayed mild attentional difficulties, restricted to selective and sustained attention domains. In conclusion, although CPT parameters differentiated the ADHD group from all others, a disorder-specific profile was not observed. (JINS, 2006, 12, 519–531.)

HIV-1-associated dementia (HIV-D) remains a significant consequence of HIV-1 infection and AIDS. Since the clinical introduction of highly active antiretroviral therapy (HAART), the incidence of HIV-D has decreased, yet the prevalence has increased as patients are living longer under treatment. Additionally, a less severe form of HIV-D, minor cognitive motor disorder, has become an increasing issue. Two different models have been proposed for virus entry in the central nervous system (CNS) in HIV-D. In the ‘Trojan horse’ model, the virus enters the CNS early carried by macrophages and infects resident glia; later in the course of infection, virus replication is activated and additional monocyte/macrophages are recruited into the CNS via cytokine/chemokine networks and endothelial-cell–leukocyte interactions at the blood–brain barrier. In the ‘late invasion’ model, an inherently invasive activated monocyte subset is expanded from bone marrow as a result of immune dysregulation in the periphery in the setting of AIDS. In this review we discuss these two separate, although not mutually exclusive, means for virus entry and persistence in the CNS. Additionally, we explore mechanisms for neuronal injury and apoptosis, including the role of virus, viral and host proteins, oxidative stress and products of infected or uninfected activated microglia and astrocytes. Potential therapeutic strategies are also briefly discussed.