Apollo Lightcraft Project

This second year of the NASA/USRA-sponsored Advanced Aeronautical Design effort focused on systems integration and analysis of the Apollo Lightcraft. This beam-powered, single-stage-to-orbit vehicle is envisioned as the shuttlecraft of the 21st century. The five person vehicle was inspired largely by the Apollo Command Module, then reconfigured to include a new front seat with dual cockpit controls for the pilot and co-pilot, while still retaining the 3-abreast crew accommodations in the rear seat. The gross liftoff mass is 5550 kg, of which 500 kg is the payload and 300 kg is the LH2 propellant. The round trip cost to orbit is projected to be three orders of magnitude lower than the current space shuttle orbiter. The advanced laser-driven 5-speed combined-cycle engine has shiftpoints at Mach 1, 5, 11 and 25+. The Apollo Lightcraft can climb into low Earth orbit in three minutes, or fly to any spot on the globe in less than 45 minutes. Detailed investigations of the Apollo Lightcraft Project this second year further evolved the propulsion system design, while focusing on the following areas: (1) man/machine interface; (2) flight control systems; (3) power beaming system architecture; (4) re-entry aerodynamics; (5) shroud structural dynamics; and (6) optimal trajectory analysis. The principal new findings are documented. Advanced design efforts for the next academic year (1988/1989) will center on a one meter+ diameter spacecraft: the Lightcraft Technology Demonstrator (LTD). Detailed engineering design and analyses, as well as critical proof-of-concept experiments, will be carried out on this small, near-term machine. As presently conceived, the LTD could be constructed using state of the art components derived from existing liquid chemical rocket engine technology, advanced composite materials, and high power laser optics

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

Impact of combined 18F-FDG PET/CT in head and neck tumours

To compare the interobserver agreement and degree of confidence in anatomical localisation of lesions using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET alone in patients with head and neck tumours. A prospective study of 24 patients (16 male, eight female, median age 59 years) with head and neck tumours was undertaken. 18F-FDG PET/CT was performed for staging purposes. 2D images were acquired over the head and neck area using a GE Discovery LS™ PET/CT scanner. 18F-FDG PET images were interpreted by three independent observers. The observers were asked to localise abnormal 18F-FDG activity to an anatomical territory and score the degree of confidence in localisation on a scale from 1 to 3 (1=exact region unknown; 2=probable; 3=definite). For all 18F-FDG-avid lesions, standardised uptake values (SUVs) were also calculated. After 3 weeks, the same exercise was carried out using 18F-FDG PET/CT images, where CT and fused volume data were made available to observers. The degree of interobserver agreement was measured in both instances. A total of six primary lesions with abnormal 18F-FDG uptake (SUV range 7.2–22) were identified on 18F-FDG PET alone and on 18F-FDG PET/CT. In all, 15 nonprimary tumour sites were identified with 18F-FDG PET only (SUV range 4.5–11.7), while 17 were identified on 18F-FDG PET/CT. Using 18F-FDG PET only, correct localisation was documented in three of six primary lesions, while 18F-FDG PET/CT correctly identified all primary sites. In nonprimary tumour sites, 18F-FDG PET/CT improved the degree of confidence in anatomical localisation by 51%. Interobserver agreement in assigning primary and nonprimary lesions to anatomical territories was moderate using 18F-FDG PET alone (kappa coefficients of 0.45 and 0.54, respectively), but almost perfect with 18F-FDG PET/CT (kappa coefficients of 0.90 and 0.93, respectively). We conclude that 18F-FDG PET/CT significantly increases interobserver agreement and confidence in disease localisation of 18F-FDG-avid lesions in patients with head and neck cancers

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

The cost of community-managed viral respiratory illnesses in a cohort of healthy preschool-aged children

Background : Acute respiratory illnesses (ARIs) during childhood are often caused by respiratory viruses, result in significant morbidity, and have associated costs for families and society. Despite their ubiquity, there is a lack of interdisciplinary epidemiologic and economic research that has collected primary impact data, particularly associated with indirect costs, from families during ARIs in children.Methods : We conducted a 12-month cohort study in 234 preschool children with impact diary recording and PCR testing of nose-throat swabs for viruses during an ARI. We used applied values to estimate a virus-specific mean cost of ARIs.Results : Impact diaries were available for 72% (523/725) of community-managed illnesses between January 2003 and January 2004. The mean cost of ARIs was AU$309 (95$263 to $354). Influenza illnesses had a mean cost of$904, compared with RSV, $304, the next most expensive single-virus illness, although confidence intervals overlapped. Mean carer time away from usual activity per day was two hours for influenza ARIs and between 30 and 45 minutes for all other ARI categories.Conclusion : From a societal perspective, community-managed ARIs are a significant cost burden on families and society. The point estimate of the mean cost of community-managed influenza illnesses in healthy preschool aged children is three times greater than those illnesses caused by RSV and other respiratory viruses. Indirect costs, particularly carer time away from usual activity, are the key cost drivers for ARIs in children. The use of parent-collected specimens may enhance ARI surveillance and reduce any potential Hawthorne effect caused by compliance with study procedures. These findings reinforce the need for further integrated epidemiologic and economic research of ARIs in children to allow for comprehensive cost-effectiveness assessments of preventive and therapeutic options.<br /

Risk Factors of Household Transmission of Pandemic (H1N1) 2009 among Patients Treated with Antivirals: A Prospective Study at a Primary Clinic in Japan

Background: Household transmission of influenza can affect the daily lives of patients and their families and be a trigger for community transmission, thus it is necessary to take precautions to prevent household transmission. We aimed to determine the risks of household transmission of pandemic (H1N1) 2009 influenza virus from an index patient who visited a primary clinic and was treated with antiviral drugs. Methods: We followed up all the patients who were diagnosed with influenza A by rapid diagnostic test with a questionnaire or interview from July 2009 to April 2010. Secondary cases were defined as patients visiting the clinic or other clinics and being positive for influenza A by rapid diagnostic test within 7 days of onset of an index patient. Logistic regression analysis was used to explore the association between household transmission and the studied variables. Results: We recruited 591 index patients and 1629 household contacts. The crude secondary attack rate was 7.3 % [95% confidence interval (CI): 6.1–8.7]. Age of index patients (0–6 years old: odds ratio 2.56; 95 % CI: 1.31–4.01; 7–12 years old: 2.44, 1.31–3.72; 30–39 years old 3.88; 2.09–5.21; 40 years old or more 2.76; 1.17–4.53) and number of household members with five or more (3.09, 2.11–4.07), medication started 48 hours from the onset of fever (2.38, 1.17–3.87) were significantly associated with household transmission. Conclusions: Household transmission was associated with index patients aged #12 years old and adults 30 years wit

Influenza vaccination coverage rates in five European countries during season 2006/07 and trends over six consecutive seasons

<p>Abstract</p> <p>Background</p> <p>The objectives of the survey were to identify the level of influenza vaccination coverage in five European countries between 2001 and 2007, to understand the drivers and barriers to vaccination, to assess vaccination intentions for the winter 2007/08 as well as major encouraging factors for vaccination.</p> <p>Methods</p> <p>Between 2001 and 2007, representative household surveys were performed with telephone or mailed (France) interviews of individuals aged 14 and above. The questionnaire used in the UK, Germany, Italy, France and Spain was essentially the same in all seasons. The data were subsequently pooled. Four target groups were defined for the analysis: 1) persons aged 65 years and over; 2) persons working in the medical field; 3) chronically ill persons and 4) combined target group composed of individuals belonging to one or more of the previous groups 1, 2 or 3.</p> <p>Results</p> <p>In 2006/07, vaccination coverage was, 25.0% in UK, 27.4% in Germany, 21.8% in Spain, 24.2% in France and 24.4% in Italy. During six influenza seasons (2001–2007), vaccination coverage showed a slight positive trend in the five countries (p ≤ 0.0001). In the elderly (≥ 65 years), across all countries, no significant trend was seen; the vaccination rate decreased non-significantly from a peak of 64.2% in season 2005/06 to 61.1% in season 2006/07. The most frequent reason for getting vaccinated was a recommendation by the family doctor or nurse (51%), and this was also perceived as the major encouraging factor for vaccination (61%). The main reason for not getting vaccinated was feeling unlikely to catch the flu (36%).</p> <p>Conclusion</p> <p>In the UK, Germany and Spain, influenza vaccination coverage rates in season 2006/07 dropped slightly compared to the previous season. However, a trend of increasing vaccination coverage was observed from 2001/02 to 2006/07 across Europe. The family doctor is the major source of encouragement for individuals getting vaccinated. Efforts to overcome the barriers to vaccination need to be put in place to reach the WHO objective of 75% coverage in the elderly by 2010. This is a major challenge to be faced by governments, healthcare workers and healthcare organisations.</p

The influenza pandemic preparedness planning tool InfluSim

BACKGROUND: Planning public health responses against pandemic influenza relies on predictive models by which the impact of different intervention strategies can be evaluated. Research has to date rather focused on producing predictions for certain localities or under specific conditions, than on designing a publicly available planning tool which can be applied by public health administrations. Here, we provide such a tool which is reproducible by an explicitly formulated structure and designed to operate with an optimal combination of the competing requirements of precision, realism and generality. RESULTS: InfluSim is a deterministic compartment model based on a system of over 1,000 differential equations which extend the classic SEIR model by clinical and demographic parameters relevant for pandemic preparedness planning. It allows for producing time courses and cumulative numbers of influenza cases, outpatient visits, applied antiviral treatment doses, hospitalizations, deaths and work days lost due to sickness, all of which may be associated with economic aspects. The software is programmed in Java, operates platform independent and can be executed on regular desktop computers. CONCLUSION: InfluSim is an online available software which efficiently assists public health planners in designing optimal interventions against pandemic influenza. It can reproduce the infection dynamics of pandemic influenza like complex computer simulations while offering at the same time reproducibility, higher computational performance and better operability

Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia

BACKGROUND: Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol). METHODS: Data were drawn from the acute phase (first 6-weeks) of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative) were measured with the Brief Psychiatric Rating Scale (BPRS), depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration. RESULTS: Weight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom), given a clinically significant weight gain (at least 7% of baseline weight), showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic response and weight gain were similar for the olanzapine and haloperidol treatment groups. Improved outcomes were, however, more pronounced for the olanzapine-treated patients, and more olanzapine-treated patients gained weight. CONCLUSIONS: The findings of significant relationships between treatment-emergent weight gain and improvements in clinical and functional status at 6-weeks suggest that patients who have greater treatment-emergent weight gain are more likely to benefit from treatment with olanzapine or haloperidol regardless of gender