The NIH plans to offer more money and more freedom to the best researchers, but there are downsides, say scientists. In July, the National Institutes of Health (NIH) Deputy Director for Extramural Research, Sally Rockey, announced on her blog, Rock Talk, that the federal agency will begin offering longer-term financial support to scientists with strong prior accomplishments, allowing them to pursue more ambitious lines of research (2). The move is a change of direction for the NIH, which has traditionally awarded research grants on the basis of specific project proposals with clear-cut scientific goals. [Extract].
The temperate waters of the North-Eastern Atlantic have a long history of maritime resource richness and, as a result, the European Union is endeavouring to maintain regional productivity and biodiversity. At the intersection of these aims lies potential conflict, signalling the need for integrated, cross-border management approaches. This paper focuses on the marine megafauna of the region. This guild of consumers was formerly abundant, but is now depleted and protected under various national and international legislative structures. We present a meta-analysis of available megafauna datasets using presence-only distribution models to characterise suitable habitat and identify spatially-important regions within the English Channel and southern bight of the North Sea. The integration of studies from dedicated and opportunistic observer programmes in the United Kingdom and France provide a valuable perspective on the spatial and seasonal distribution of various taxonomic groups, including large pelagic fishes and sharks, marine mammals, seabirds and marine turtles. The Western English Channel emerged as a hotspot of biodiversity for megafauna, while species richness was low in the Eastern English Channel. Spatial conservation planning is complicated by the highly mobile nature of marine megafauna, however they are important components of the marine environment and understanding their distribution is a first crucial step toward their inclusion into marine ecosystem management.
The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders and together are the most common degenerative brain diseases in childhood. They are a group of disorders linked by the characteristic accumulation of abnormal storage material in neurons and other cell types, and a degenerative disease course. All NCLs are characterized by a combination of dementia, epilepsy, and motor decline. For most childhood NCLs, a progressive visual failure is also a core feature. The characteristics of these symptoms can vary and the age at disease onset ranges from birth to young adulthood. Genetic heterogeneity, with fourteen identified NCL genes and wide phenotypic variability render diagnosis difficult. A new NCL classification system based on the affected gene and the age at disease onset allows a precise and practical delineation of an individual patients NCL type. A diagnostic algorithm to identify each NCL form is presented here. Precise NCL diagnosis is essential not only for genetic counseling, but also for the optimal delivery of care and information sharing with the family and other caregivers. These aspects are challenging because there are also potential long term complications which are specific to NCL type. Therefore care supported by a specifically experienced team of clinicians is recommended. As the underlying pathophysiological mechanism is still unclear for all NCL forms, the development of curative therapies remains difficult. This article is part of a Special Issue entitled: The neuronal ceroid lipofuscinoses or Batten Disease.
It has been shown experimentally that competition for limited translational resources by upstream mRNAs can lead to an anticorrelation between protein counts. Here, we investigate a stochastic model for this phenomenon, in which gene transcripts of different types compete for a finite pool of ribosomes. Throughout, we utilize concepts from the theory of multiclass queues to describe a qualitative shift in protein count statistics as the system transitions from being underloaded (ribosomes exceed transcripts in number) to being overloaded (transcripts exceed ribosomes in number). The exact analytical solution of a simplified stochastic model, in which the numbers of competing mRNAs and ribosomes are fixed, exhibits weak positive correlations between steady-state protein counts when total transcript count slightly exceeds ribosome count, whereas the solution can exhibit strong negative correlations when total transcript count significantly exceeds ribosome count. Extending this analysis, we find approximate but reasonably accurate solutions for a more realistic model, in which abundances of mRNAs and ribosomes are allowed to fluctuate randomly. Here, ribosomal fluctuations contribute positively and mRNA fluctuations contribute negatively to correlations, and when mRNA fluctuations dominate ribosomal fluctuations, a strong anticorrelation extremum reliably occurs near the transition from the underloaded to the overloaded regime.
This article explores the development of the Butterfly Scheme, a hospital-based, dementia-specific programme that aims to improve patient safety and wellbeing. Carer Barbara Hodkinson developed the initiative, which is an opt-in programme of care that identifies people with memory impairment, with their permission, by a butterfly symbol on their name board and notes. It also ensures carers are asked for detailed information about their relatives, such as their likes and dislikes and aspects of their daily and past life, and seeks to educate staff to interact knowledgeably, positively and appropriately using a five-point response system. Two case studies from hospitals which have introduced the scheme are presented.
The aim of this study was to evaluate whether pediatric bone marrow transplant (BMT) patients receive the prescribed dose of nutrition support (NS). Data were obtained from electronic and paper charts at St. Jude Childrens Research Hospital. The amount of NS received was compared with the amount prescribed. Data were collected on 32 patients for 63 hospital stays in which NS was administered. The mean percentage of nutrition prescription met and percentage of total estimated energy met were 69% and 72%, respectively. Allogeneic BMT patients received significantly more of their nutrition prescription (92%) than autologous BMT patients did (54%, P < .01). Malnourished patients were significantly more likely to receive the full dose of NS than patients who were considered nourished or obese (P < .05). This study showed that patients who were most in need of NS were more likely to receive the full dose.
Chief nursing officer for England Dame Chris Beasley retires this month. She is known best for achieving cuts in healthcare-associated infection rates and reducing mixed-sex wards. But she has also worked to give nurses a higher profile in the NHS and most recently pioneered the development of the high impact actions for nursing and midwifery.
The neuropeptide nocistatin has a variety of effects on nociception and other central nervous system functions. It has shown to exert diverging effects on nociceptive behavior in various experimental pain models depending on the dose administered. The inhibitory effect of spinal nocistatin on the release of glycine and ?-aminobutyric acid is thought to be responsible for pronociceptive effects, whereas the antinociceptive action of nocistatin can be attributed to diminished glycine-dependent N-methyl-D-aspartate receptor activation. So far, nocistatin has only been investigated in experimental models of already established pain and has been injected as a bolus.
High-throughput technologies have led to the generation of complex wiring diagrams as a post-sequencing paradigm for depicting the interactions between vast and diverse cellular species. While these diagrams are useful for analyzing biological systems on a large scale, a detailed understanding of the molecular mechanisms that underlie the observed network connections is critical for the further development of systems and synthetic biology. Here, we use queueing theory to investigate how waiting lines can lead to correlations between protein customers that are coupled solely through a downstream set of enzymatic servers. Using the E. coli ClpXP degradation machine as a model processing system, we observe significant cross-talk between two networks that are indirectly coupled through a common set of processors. We further illustrate the implications of enzymatic queueing using a synthetic biology application, in which two independent synthetic networks demonstrate synchronized behavior when common ClpXP machinery is overburdened. Our results demonstrate that such post-translational processes can lead to dynamic connections in cellular networks and may provide a mechanistic understanding of existing but currently inexplicable links.
Acinetobacter baumannii infection is responsible for a wide range of infections, including pneumonia, bacteraemia, meningitis, wound infections, and urinary tract infections. During June 2010, two patients on an intensive care unit in an acute hospital in the UK had multi-resistant A. baumannii identified in samples obtained from a variety of specimens. A further case was identified 31 days following confirmation of the first outbreak. The investigation and management of this outbreak included the introduction of enhanced infection prevention and control precautions; the establishment of an Outbreak Control Team; epidemiological investigations; and the decontamination of equipment and the environment. Isolate typing by the Health Protection Agency Centre for Infections laboratory confirmed the three cases had identical A. baumannii strains: European clone II lineage encoded with an OXA-51-type carbapenemase. This suggests that there was a patient-to-patient spread of multi-resistant A. baumannii.
A 61-year-old woman was admitted with history of vomiting, diarrhoea and severe hyponatraemia (Na(+) 109). The cause of the hyponatraemia was due to intravascular volume depletion resulting in a non-osmotic release of antidiuretic hormone (ADH) with the added effects of a thiazide diuretic. She was also on fluoxetine which may induce inappropriate secretion of ADH. Despite cautious fluid replacement, the patients serum sodium increased by 12 mmol/l over the first 18 h (and by 10 mmol/l over 12 h). This trajectory, coupled with the rapid decrease in urine osmolality, suggested that this patient was at risk of significant brain injury due to rapid correction of serum sodium. The use of desmopressin slowed the rise in serum sodium allowing brain adaptive mechanisms time to protect against osmotic demyelination.
Due to the dearth of relevant research, intellectual disability nurses may have difficulty identifying sources of evidence on which they can base their clinical decisions. The aim of the present research was to explore how intellectual disability nurses make decisions and how their decisions are influenced by evidence. The method was guided by interpretative phenomenology and the analysis adopted an idiographic approach. Twelve National Health Service intellectual disability nurses in Wales participated in semi-structured interviews. Four key themes were identified: getting to know the person; working as a team; evidence to support decision making; and understanding of evidence-based practice. In the context of the myriad of other professionals involved in caregiving, the nurses conveyed a commitment towards ensuring that the person with intellectual disability is at the centre of decision making. Although using empirical evidence to support practice was acknowledged, these nurses considered person centred decision making to be paramount.
Deepak Srivastava’s group at the Gladstone Institute of Cardiovascular Disease, University of California San Francisco, reported in the August 6 issue of the journal Cell that to make heart muscle cells, all you need are three factors and some fibroblasts. But is it really that easy?
The purpose is to answer the following research question: are the time-series data published by the Australian Bureau of Statistics for Queensland statistically the same as those of the Queensland Suicide Register?
A major challenge for systems biology is to deduce the molecular interactions that underlie correlations observed between concentrations of different intracellular molecules. Although direct explanations such as coupled transcription or direct protein-protein interactions are often considered, potential indirect sources of coupling have received much less attention. Here we show how correlations can arise generically from a posttranslational coupling mechanism involving the processing of multiple protein species by a common enzyme. By observing a connection between a stochastic model and a multiclass queue, we obtain a closed form expression for the steady-state distribution of the numbers of molecules of each protein species. Upon deriving explicit analytic expressions for moments and correlations associated with this distribution, we discover a striking phenomenon that we call correlation resonance: for small dilution rate, correlations peak near the balance-point where the total rate of influx of proteins into the system is equal to the maximum processing capacity of the enzyme. Given the limited number of many important catalytic molecules, our results may lead to new insights into the origin of correlated behavior on a global scale.
Dietary fluid and sodium intake may influence the risk for vasoocclusive events in persons with sickle cell anemia (SCA). The objective of this study was to examine the dietary intake of water and sodium in children and adolescents with SCA and identify possible factors influencing intake. We compared water (mL) and sodium (mg) intake in 21 patients with SCA, aged 5 to 18 years, to reported adequate intake for water, daily fluid requirement, upper limit for sodium, and National Health and Nutrition Examination Survey 2005 to 2006 data for sodium, and sociodemographic factors. Dietary intake from 3-day food records was evaluated retrospectively. Median water intake was significantly lower than adequate intake, and median sodium intake was significantly higher than sodium upper limit. Sociodemographic factors were not associated with dietary water or sodium intake. Our results suggest that children and adolescents with SCA would benefit from education regarding increasing fluid intake and limiting high sodium foods.
Rising suicide rates have been identified as a social problem in several Western countries. The application of a Welfare Economics argument justifies a role for policy that reduces the welfare impact of suicide, whereas the measurement of that impact can inform policy making. Two dimensions of the concept can be measured: the social loss from suicide, and the inequality in the distribution of that loss. In this study, an alternative measure of suicide to the conventional suicide headcount, viz. the potential years of life lost (PYLL), is employed. The PYLL measure is a proxy measure of the social impact of suicide, and involves the concept of premature loss of life. The PYLL also lends itself to inequality measurement. We apply the approach to inequality measurement of health phenomena that was pioneered in the 1980s by Jacques Silber and Julian Le Grand, in a literature now described as measuring health inequality per se. The empirical part of the paper statistically estimates equations on Australian suicide data for the period 1907-2003 and determines the trends in the social loss from suicide and the inequality of its age distribution. Some illustrative examples assist in interpreting the welfare impact of suicide measured both ways, by the headcount rate and the PYLL rate.
The nurse consultant role has existed for a decade. The five components of the role--professional leadership, service development, research, education and training, and expert practice--are discussed in relation to Aileen Frasers work with older people in Bristol. Ms Fraser explains how she has identified gaps in services and developed new policies to improve practice on safeguarding vulnerable adults. She also discusses how she has been influenced by good practice she witnessed on a study tour in the United States.
Resource shortages and unmet need are two economic problems reported in the Australian mental health sector. Unmet need arises with a structural imbalance, the non-correspondence between the use of mental health services and the extent of need for those services. Another problem reported in literature is met non-need, people who use mental health services and do not have a diagnosis of mental illness.
This study determines the trend in mental health-related mortality (defined here as the aggregation of suicide and deaths coded as "mental/behavioural disorders"), and its relative numerical importance, and to argue that this has importance to policy-makers. Its results will have policy relevance because policy-makers have been predominantly concerned with cost-containment, but a re-appraisal of this issue is occurring, and the trade-off between health expenditures and valuable gains in longevity is being emphasised now. This study examines longevity gains from mental health-related interventions, or their absence, at the population level. The study sums mortality data for suicide and mental/behavioural disorders across the relevant ICD codes through time in Australia for the period 1916-2004. There are two measures applied to the mortality rates: the conventional age-standardised headcount; and the age-standardised Potential Years of Life Lost (PYLL), a measure of premature mortality. Mortality rates formed from these data are analysed via comparisons with mortality rates for All Causes, and with circulatory diseases, cancer and motor vehicle accidents, measured by both methods.
Every chromosome needs a centromere for proper segregation during cell division. Centromeric chromatin wraps around histones, providing an anchor for kinetochore proteins and spindle attachment. It is clear why cells need centromeres, but how they form and what they look like is less so. Recent reports extend our understanding of chaperones involved in centromere formation. And other accounts of half-sized, right-handed nucleosomes have created an unexpected twist.
Concern with suicide measurement is a positive, albeit relatively recent, development. A concern with "the social loss from suicide" requires careful attention to appropriately measuring the phenomenon. This paper applies two different methods of measuring suicide data: the conventional age-standardized suicide (count) rate; and the alternative rate, the potential years of life lost (PYLL) rate.
The neuronal ceroid lipofuscinoses (NCL) are a group of genetically heterogeneous neurodegenerative disorders. The recent identification of the MFSD8/CLN7 gene in a variant-late infantile form of NCL (v-LINCL) in affected children from Turkey prompted us to examine the relative frequency of variants in this gene in Italian patients with v-LINCL. We identified nine children harboring 11 different mutations in MFSD8/CLN7. Ten mutations were novel and included three nonsense (p.Arg35Stop, p.Glu381Stop, p.Arg482Stop), four missense (p.Met1Thr, p.Gly52Arg, p.Thr294Lys, p.Pro447Leu), two splice site mutations (c.863+3_4insT, c.863+1G>C), and a 17-bp deletion predicting a frameshift and premature protein truncation (c.627_643del17/p.Met209IlefsX3). The clinical phenotype, which was similar to that of the Turkish v-LINCL cases, was not influenced by type and location of the mutation nor the length of the predicted residual gene product. As well as identifying novel variants in MFSD8/CLN7, this study contributes to a better molecular characterization of Italian NCL cases, and will facilitate medical genetic counseling in such families. The existence of a subset of v-LINCL cases without mutations in any of the known NCL genes suggests further genetic heterogeneity.
We reconsider conventional suicide measurement. First, a headcount of suicide is examined relative to some other causes of death (circulatory diseases, cancer, and motor vehicle accidents). We then construct a time-series data set of an alternative measure of suicide, the potential years of life lost (PYLL) for males and females. Suicide PYLLs average 4.57% of all male PYLLs and 2.44% of female PYLLs for 1907-2005. The comparable "count" percentages are 1.85 and 0.65, respectively. These differences are widening through time. In 2005, suicide represented 3.25% of all male deaths and 0.90% of female deaths using the count measure and, using PYLLs, 11.0% and 4.96%, respectively. The two measures produce quite different indications of suicide.
Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives.
Who are the ophthalmologists of the future? How will the new generation practice? How will they interact with their professional organizations? What part will technology play in their lives and professions? A new paradigm is in place that will dramatically affect ophthalmologists answers to these questions going forward. Given the uncertainty of our future professional lives, it is vital that we anticipate, contemplate, and formulate a plan. To begin this process, the Knapp Symposium at the 2011 Annual Meeting of the American Ophthalmological Society was devoted to a discussion of the ophthalmologist of the future.
This article provides five case studies to illustrate the increasing involvement of nurses in ambulance services in England and Wales, and how their work complements that of their paramedic colleagues to improve care delivery.
We provide a new classification for the neuronal ceroid lipofuscinoses (NCLs) that takes into account recent genetic and biochemical advances. This was originally developed by an international group with clinical, molecular genetic, biological, and morphologic interests, further revised by a panel of world experts in the NCLs, and is now updated in light of recent research findings. The aim is to provide young people, carers, and professionals with a diagnostic label that is informative, leads to effective clinical management of symptoms and in the future perhaps a cure, as well as aiding basic scientific and clinical research. We suggest that clinicians should aim to provide every child and family with detailed diagnostic information at clinical, biochemical, and genetic levels where possible, which the new classification allows in a gene-led hierarchical manner. The robustness and applicability of this updated new classification have been independently audited in the clinical setting using a series of patients previously diagnosed with NCL according to standard ultrastructural, biochemical, or genetic criteria.
Nurses are increasingly becoming involved in ambulance services in England and Wales. This article discusses some of the work they do and why their involvement is important in improving the delivery of emergency care to patients.
Weight gain after kidney transplantation affects 50% to 90% of kidney transplant recipients. Factors leading to weight gain in recipients are thought to include a change in lifestyle (eg, dietary intake and physical activity), age, race, sex, and immunosuppressant medications.
A stroke specialist nurse enlisted the help of women carers to develop a self-supporting carers group in Northern Ireland. Members are offered information, advice and a forum for service improvement suggestions. Two founding members discuss their experiences of attending meetings.
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