Accelerating vaccine development and deployment: report of a Royal Society satellite meeting.

The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it

Alcohol-related dementia: An update of the evidence

The characteristics of dementia relating to excessive alcohol use have received increased research interest in recent times. In this paper, the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and alcohol-induced persisting amnestic syndrome (Wernicke-Korsakoff syndrome, or WKS) are reviewed. Neuropathological and imaging studies suggest that excessive and prolonged use of alcohol may lead to structural and functional damage that is permanent in nature; however, there is debate about the relative contributions of the direct toxic effect of alcohol (neurotoxicity hypothesis), and the impact of thiamine deficiency, to lasting damage. Investigation of alcohol-related cognitive impairment has been further complicated by differing definitions of patterns of alcohol use and associated lifestyle factors related to the abuse of alcohol. Present diagnostic systems identify two main syndromes of alcohol-related cognitive impairment: ARD and WKS. However, 'alcohol-related brain damage' is increasingly used as an umbrella term to encompass the heterogeneity of these disorders. It is unclear what level of drinking may pose a risk for the development of brain damage or, in fact, whether lower levels of alcohol may protect against other forms of dementia. Epidemiological studies suggest that individuals with ARD typically have a younger age of onset than those with other forms of dementia, are more likely to be male, and often are socially isolated. The cognitive profile of ARD appears to involve both cortical and subcortical pathology, and deficits are most frequently observed on tasks of visuospatial function as well as memory and higher-order (executive) tasks. The WKS appears more heterogeneous in nature than originally documented, and deficits on executive tasks commonly are reported in conjunction with characteristic memory deficits. Individuals with alcohol-related disorders have the potential to at least partially recover - both structurally and functionally - if abstinence is maintained. In this review, considerations in a clinical setting and recommendations for diagnosis and management are discussed. It is well established that excessive and prolonged alcohol use can lead to permanent damage to the structure and function of the brain [1]. Despite this, there is little consensus on the characteristics of a dementia syndrome related to sustained alcohol abuse or its relationship to Wernicke-Korsakoff syndrome (WKS). After a long period of neglect, research interest has increased in recent years and has been spurred on by clinical demand, increased reported rates of alcohol abuse in older people, and increasing alcohol consumption by women [2, 3]. In this paper, we aim to review the neuropathology, nosology, epidemiology, clinical features, and neuropsychology of alcohol-related dementia (ARD) and WKS. To retrieve papers for the purpose of this review, the search terms (alcohol OR alcoholism) AND (dementia OR brain damage OR brain injury OR cognitive impairment) were used as keywords in the Medline and PsycINFO databases. Additional terms included Wernicke's encephalopathy, Korsakoff, and Alcohol Amnestic Disorder. Reference lists were also scanned for relevant papers

Cross-sector collaboration among critical infrastructure utilities : a case study for assessing relational capacity

CHDS State/LocalThis nation relies on the network of critical infrastructures to maintain economic superiority, public health, and military strength. Under this premise, the federal government established the National Infrastructure Protection Plan (NIPP) to leverage national and regional preparedness. Hurricane Katrina demonstrated that, collectively, the infrastructure sectors are not prepared to respond to local and regional disasters using national strategies and resources. There remains a lack of capability to assess an organization's capacity to collaborate. To better understand the enablers and barriers to collaboration within a region's infrastructure system, this study reports the findings of interviews of thirteen middle and ten top managers of the utility organizations in and around Mesa, Arizona. In addition to interviews, the managers in this case study completed a survey on collaborative capacity that provides a lens for examining the factors that enable and impede cross-sector collaboration in the City of Mesa and the interdependent sectors. Finally, the managers were requested to provide individual interpretations of the survey data and recommendations for improvement on the "Response Form." Incorporating this feedback will be critical for starting the momentum for change.http://archive.org/details/crosssectorcolla109453314Wastewater Compliance Administrator, City of Mesa, Arizona, Utility Department author (civilian)

Characterization of mid-intestinal microbiota of farmed Chinook salmon using 16S rRNA gene metabarcoding

With the growing importance of aquaculture worldwide, characterization of the microbiota of high-value aquaculture species and identification of their shifts induced by changes in fish physiology or nutrition is of special interest. Here we report the first 16S rRNA gene metabarcoding survey of the mid-intestinal bacteria of Chinook salmon (Oncorhynchus tshawytscha), an economically important aquacultured species. The microbiota of 30 farmed Chinook salmon from a single cohort was surveyed using metabarcode profiling of the V3-V4 hypervariable region of the bacterial 16S rRNA gene. Seawater, feed and mid-intestinal samples and controls were sequenced in quadruplicate to assess both biological and technical variation in the microbial profiles. Over 1000 operational taxonomic units were identified within the cohort, providing a first glimpse into the mid-intestinal microbiota of farmed Chinook salmon. The taxonomic distribution of the salmon microbiota was reasonably stable, with around two thirds of individuals dominated by members of the family Vibrionaceae. We anticipate that the workflow presented in this paper could be applied in other aquacultured fish species to capture variation or dysbiosis occurring as a result of changes in feed, health or environmental conditions

ΦCrAss001 represents the most abundant bacteriophage family in the human gut and infects Bacteroides intestinalis

peer-reviewedCrAssphages are an extensive and ubiquitous family of tailed bacteriophages, predicted to infect bacteria of the order Bacteroidales. Despite being found in ~50% of individuals and representing up to 90% of human gut viromes, members of this viral family have never been isolated in culture and remain understudied. Here, we report the isolation of a CrAssphage (ΦCrAss001) from human faecal material. This bacteriophage infects the human gut symbiont Bacteroides intestinalis, confirming previous in silico predictions of the likely host. DNA sequencing demonstrates that the bacteriophage genome is circular, 102 kb in size, and has unusual structural traits. In addition, electron microscopy confirms that ΦcrAss001 has a podovirus-like morphology. Despite the absence of obvious lysogeny genes, ΦcrAss001 replicates in a way that does not disrupt proliferation of the host bacterium, and is able to maintain itself in continuous host culture during several weeks

Help-seeking experiences of bereaved adolescents: A qualitative study

Despite the potentially devastating effects of a death on the lives of adolescents, little is known about their help-seeking experiences. We interviewed by telephone 39 bereaved adolescents on their help-seeking experiences. Thematic analysis resulted in three themes: Formal support, Informal support and School-related support. Participants provided a critical appraisal of positive and negative experiences, and noted barriers and facilitators for help-seeking. As adolescents bereaved through suicide may receive less social support, professional help is a much needed auxiliary. Parental encouragement is important in accessing adequate professional help

Single- and double-scattering production of four muons in ultraperipheral PbPb collisions at the Large Hadron Collider

We discuss production of two $\mu^+\mu^-$ pairs in ultraperipheral ultrarelativistic heavy ion collisions at the LHC. We take into account electromagnetic (two-photon) double-scattering production and for a first time direct $\gamma\gamma$ production of four muons in one scattering. We study the unexplored process $\gamma \gamma \to \mu^+\mu^-\mu^+\mu^-$. We present predictions for total and differential cross sections. Measurable nuclear cross sections are obtained and corresponding differential distributions and counting rates are presented.Comment: 13 pages, 11 figures, 1 tabl

Potentially preventable complications of urinary tract infections, pressure areas, pneumonia, and delirium in hospitalised dementia patients: Retrospective cohort study

OBJECTIVES: To identify rates of potentially preventable complications for dementia patients compared with non-dementia patients. DESIGN: Retrospective cohort design using hospital discharge data for dementia patients, case matched on sex, age, comorbidity and surgical status on a 1 : 4 ratio to non-dementia patients. SETTING: Public hospital discharge data from the state of New South Wales, Australia for 2006/2007. PARTICIPANTS: 426 276 overnight hospital episodes for patients aged 50 and above (census sample). MAIN OUTCOME MEASURES: Rates of preventable complications, with episode-level risk adjustment for 12 complications that are known to be sensitive to nursing care. RESULTS: Controlling for age and comorbidities, surgical dementia patients had higher rates than non-dementia patients in seven of the 12 complications: urinary tract infections, pressure ulcers, delirium, pneumonia, physiological and metabolic derangement (all at p<0.0001), sepsis and failure to rescue (at p<0.05). Medical dementia patients also had higher rates of these complications than did non-dementia patients. The highest rates and highest relative risk for dementia patients compared with non-dementia patients, in both medical and surgical populations, were found in four common complications: urinary tract infections, pressure areas, pneumonia and delirium. CONCLUSIONS: Compared with non-dementia patients, hospitalised dementia patients have higher rates of potentially preventable complications that might be responsive to nursing interventions

Falls, Depression and antidepressants in Later Life: A Large Primary Care Appraisal

Background: Depression and falls are common and co-exist for older people. Safe management of each of these conditions is important to quality of life. Methods: A cross-sectional survey was used to examine medication use associated with injurious and non-injurious falls in 21,900 community-dwelling adults, aged 60 years or over from 383 Australian general practices recruited for the DEPS-GP Project. Falls and injury from falls, medication use, depressive symptoms (Primary Health Questionnaire (PHQ-9)), clinical morbidity, suicidal ideation and intent, health status (SF-12 Health Survey), demographic and lifestyle information was reported in a standardised survey. Findings: Respondents were 71.8 years (sd 7.7) of age and 58.4% were women. 24% 11% and 8% reported falls, fall related injury, and sought medical attention respectively. Antidepressant use (odds ratio, OR: 1.46; 95% confidence interval, 95%CI: 1.25, 1.70), questionable depression (5–14 on PHQ OR: 1.32, 95%CI: 1.13, 1.53) and clinically significant symptoms of depression (15 or more on PHQ OR: 1.70, 95%CI: 1.14, 1.50) were independently associated with multiple falls. SSRI use was associated with the highest risk of multiple falls (OR: 1.66, 95%CI: 1.36, 2.02) amongst all psychotropic medications. Similar associations were observed for injurious falls. Over 60% of those with four accumulated risk factors had multiple falls in the previous year (OR: 3.40, 95%CI: 1.79, 6.45); adjusted for other demographic and health factors. Interpretation: Antidepressant use (particularly SSRIs) was strongly associated with falls regardless of presence of depressive symptoms. Strategies to prevent falls should become a routine part of the management of older people with depression

Levels of physical activity and sleep patterns among older people with dementia living in long-term care facilities: A 24-hour snapshot

Objectives To objectively measure over a 24-hour period the daytime and nighttime levels of physical activity and sleep patterns of older people with dementia living in long-term care facilities. Study design Nested within a larger research program, this cross-sectional study involved 415 residents, aged ≥60 years, with a documented diagnosis of dementia, from 28 long-term care facilities in south-east Queensland, Australia. Main outcome measures Residents wore SenseWear® activity armbands continuously for 24 hours, with data recorded for: step count; total energy expenditure; metabolic equivalent of task (MET); and the amount of time spent physically active, lying down, awake and asleep. Residents’ levels of cognitive impairment (assessed using the Rowland Universal Dementia Assessment Scale) and agitation (assessed using the Cohen-Mansfield Agitation Inventory-Short Form), and demographic data were also collected. Results From a total of 415 residents monitored with the SenseWear® activity armbands, 192 met the valid wear-time of 21 hours or more, and had activity and sleep data recorded. These residents were largely inactive during the daytime (engaged in an average of 1.8 hours of light physical activity), but achieved recommended amounts of sleep at night (average of 6.8 hours). There was considerable variation within the sample, and activity and sleep differed by sex (p<.001), age (p=.010), mobility (p<.001), and antipsychotic usage (p=.030). Conclusions These data can be used by long-term care clinicians to assist in planning interventions and care approaches which promote physical activity and good sleep practices, and are individualized to physical and cognitive capabilities. Australian New Zealand Clinical Trials Registry (ACTRN12614000508673).NHMR