To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
In the past four decades lipid vesicles (liposomes) have evolved from widely used biomembrane models into important drug and gene carriers. The phosphatidylcholine phospholipids PC used in the drug carriers are biocompatible and biodegradable but they function as a relatively inert shell and require the incorporation of cholesterol to maintain the drug encapsulated in the liposome; The PC are also incapable of associating with ligands and have very weak interactions with nucleic acids. Moreover, they are not particularly good for cytoplasmic delivery of the encapsulated cargo. Recently, we have devised three classes of new lipids and have improved the synthesis of a fourth class that enable the preparation of a bioresponsive targeted carrier with improved nucleic acid delivery. Class 1 are low pH sensitive and include a diortho ester PEG lipid or a di-orthoester PC. Class two are redox sensitive lipids and include thiocholesterol based and thio diacyl chain based lipids that can be used in a sequential assembly process to encapsulate nucleic acid drugs in a charge neutral or negatively charged nanolipid particle. Class 3 is a new family of lipids that provide increased in vivo bilayer stability without the need for crosslinking of the bilayer. Class 4 is an improved synthesis of a triNTA diacyl lipid. This lipid can be used to attach His-6 containing molecules to the bilayer vesicle after the liposomes have been prepared and loaded with drugs. These lipids form a tool kit that can be used to prepare a variety of targeted drug, protein and nucleic acid delivery vesicles with attached targeting ligands. The synthesis, characterization and use of these lipids in a variety of drug delivery applications will be described. Suported by NIH EB003008 & NIH GM061851.
Timely identification of outbreaks of hospital-associated infections is needed to implement control measures and minimize impact. Survey results from 33 hospitals indicated that most hospitals lacked a formal cluster definition and all targeted a very limited group of prespecified pathogens. Standardized, statistically based outbreak detection could greatly improve current practice.
Infect. Control Hosp. Epidemiol. 2016;37(4):466–468
To estimate and compare the impact on healthcare costs of 3 alternative strategies for reducing bloodstream infections in the intensive care unit (ICU): methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, targeted decolonization (ie, screening, isolation, and decolonization of MRSA carriers or infections), and universal decolonization (ie, no screening and decolonization of all ICU patients).
Cost analysis using decision modeling.
We developed a decision-analysis model to estimate the health care costs of targeted decolonization and universal decolonization strategies compared with a strategy of MRSA nares screening and isolation. Effectiveness estimates were derived from a recent randomized trial of the 3 strategies, and cost estimates were derived from the literature.
In the base case, universal decolonization was the dominant strategy and was estimated to have both lower intervention costs and lower total ICU costs than either screening and isolation or targeted decolonization. Compared with screening and isolation, universal decolonization was estimated to save $171,000 and prevent 9 additional bloodstream infections for every 1,000 ICU admissions. The dominance of universal decolonization persisted under a wide range of cost and effectiveness assumptions.
A strategy of universal decolonization for patients admitted to the ICU would both reduce bloodstream infections and likely reduce healthcare costs compared with strategies of MRSA nares screening and isolation or screening and isolation coupled with targeted decolonization.
Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10–11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10–11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.
Carbon-based forest conservation requires the establishment of ‘reference emission levels’ against which to measure a country or region's progress in reducing their carbon emissions. In East Africa, landscape-scale estimates of carbon fluxes are uncertain and factors such as deforestation poorly resolved due to a lack of data. In this study, trends in vegetation cover and carbon for East Africa were quantified using moderate-resolution imaging spectroradiometer (MODIS) land cover grids from 2002 to 2008 (500-m spatial resolution), in combination with a regional carbon look-up table. The inclusion of data on rainfall and the distribution of protected areas helped to gauge impacts on vegetation burning (assessed using 1-km spatial resolution MODIS active fire data) and biome trends. Between 2002 and 2008, the spatial extents of forests, woodlands and scrublands decreased considerably and East Africa experienced a net carbon loss of 494 megatonnes (Mt). Most countries in the area were sources of carbon emissions, except for Tanzania and Malawi, where the areal increase of savannah and woodlands counterbalanced carbon emissions from deforestation. Both Malawi and Tanzania contain large areas of planted forest. Vegetation burning was correlated with rainfall (forest only) and differed depending on land management. Freely available global earth observation products have provided ways to achieve rapid assessment and monitoring of carbon change hotspots at the landscape scale.
Since hospitals in a region often share patients, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in one hospital could affect other hospitals.
Using extensive data collected from Orange County (OC), California, we developed a detailed agent-based model to represent patient movement among all OC hospitals. Experiments simulated MRSA outbreaks in various wards, institutions, and regions. Sensitivity analysis varied lengths of stay, intraward transmission coefficients (β), MRSA loss rate, probability of patient transfer or readmission, and time to readmission.
Each simulated outbreak eventually affected all of the hospitals in the network, with effects depending on the outbreak size and location. Increasing MRSA prevalence at a single hospital (from 5% to 15%) resulted in a 2.9% average increase in relative prevalence at all other hospitals (ranging from no effect to 46.4%). Single-hospital intensive care unit outbreaks (modeled increase from 5% to 15%) caused a 1.4% average relative increase in all other OC hospitals (ranging from no effect to 12.7%).
MRSA outbreaks may rarely be confined to a single hospital but instead may affect all of the hospitals in a region. This suggests that prevention and control strategies and policies should account for the interconnectedness of health care facilities.
Ecological regions aggregate habitats with similar biophysical characteristics within well-defined boundaries, providing spatially consistent platforms for monitoring, managing and forecasting the health of interrelated ecosystems. A major obstacle to the implementation of this approach is imprecise and inconsistent boundary placement. For globally important mountain regions such as the Eastern Arc (Tanzania and Kenya), where qualitative definitions of biophysical affinity are well established, rule-based methods for landform classification provide a straightforward solution to ambiguities in region extent. The method presented in this paper encompasses the majority of both contemporary and estimated preclearance forest cover within strict topographical limits. Many of the species here tentatively considered ‘near-endemic’ could be reclassified as strictly endemic according to the derived boundaries. LandScan and census data show population density inside the ecoregion to be higher than in rural lowlands, and lowland settlement to be most probable within 30 km. This definition should help to align landscape scale conservation strategies in the Eastern Arc and promote new research in areas of predicted, but as yet undocumented, biological importance. Similar methods could work well in other regions where mountain extent is poorly resolved. Spatial data accompany the online version of this article.
We report on high quality Ba1−xKxBiO3 (BKBO) thin films grown by pulsed laser deposition. The best films exhibit resistive and magnetic transition temperatures of 28 K, with a transition width of 0.4 K and critical current densities above 106 A/cm2 measured at 5 K. Surface impedance is measured to be 1 mΩ. Films are single phase and highly oriented in the (100) direction and electron diffraction shows no other phases. Analysis using Moire' fringes shows films to consist of 100 nm size dislocation-free regions which show a high degree of in-plane epitaxy.
Isolates of Salmonella typhimurium, recovered over a 9-month period from a child with gastroenteritis, were characterized by biotyping, phage-typing and plasmid-profile analysis. Because the data from the different methods were discrepant, it was difficult to establish whether her infection was due to a single strain that had changed character in vivo or was due to recurrent infections with different, unrelated strains. Restriction-enzyme fingerprinting of the plasmids from the different isolates provided an explanation for the initial discrepancy and highlighted a source of potential confusion in epidemiological studies.
Antimicrobial resistance is a priority emerging public health threat, and the ability to detect promptly outbreaks caused by resistant pathogens is critical for resistance containment and disease control efforts. We describe and evaluate the use of an electronic laboratory data system (WHONET) and a space–time permutation scan statistic for semi-automated disease outbreak detection. In collaboration with WHONET-Argentina, the national network for surveillance of antimicrobial resistance, we applied the system to the detection of local and regional outbreaks of Shigella spp. We searched for clusters on the basis of genus, species, and resistance phenotype and identified 19 statistical ‘events’ in a 12-month period. Of the six known outbreaks reported to the Ministry of Health, four had good or suggestive agreement with SaTScan-detected events. The most discriminating analyses were those involving resistance phenotypes. Electronic laboratory-based disease surveillance incorporating statistical cluster detection methods can enhance infectious disease outbreak detection and response.
The space–time scan statistic is often used to identify incident disease clusters. We introduce a method to adjust for naturally occurring temporal trends or geographical patterns in illness. The space–time scan statistic was applied to reports of lower respiratory complaints in a large group practice. We compared its performance with unadjusted populations from: (1) the census, (2) group-practice membership counts, and on adjustments incorporating (3) day of week, month, and holidays; and (4) additionally, local history of illness. Using a nominal false detection rate of 5%, incident clusters during 1 year were identified on 26, 22, 4 and 2% of days for the four populations respectively. We show that it is important to account for naturally occurring temporal and geographic trends when using the space–time scan statistic for surveillance. The large number of days with clusters renders the census and membership approaches impractical for public health surveillance. The proposed adjustment allows practical surveillance.
The Critically Endangered Burmese star tortoise Geochelone platynota is endemic to the dry zone of central Myanmar. Although quantitative assessments are lacking, populations are believed to be in decline throughout its limited range due to over-collecting for international markets. We conducted star tortoise surveys during 2000–2001 at two sites in central Myanmar: Minzontaung Wildlife Sanctuary, a protected area established in 1998–1999, and Myaleik Taung, an area recently proposed for protected status. G. platynota populations of global conservation significance were found at both sites. Because tortoises are protected by local religious beliefs and commercial collecting is so far non-existent, the Sanctuary and Myaleik Taung offer excellent prospects for star tortoise conservation. The Sanctuary is well patrolled, protected from wildfires, and access is rigorously controlled. Recommended conservation actions at Myaleik Taung include management of livestock grazing, prescribed burning, and elimination of fuelwood cutting.
Recent stratigraphic studies in central Alaska have yielded the unexpected finding that there is little evidence for full-glacial (late Wisconsin) loess deposition. Because the loess record of western Alaska is poorly exposed and not well known, we analyzed a core from Zagoskin Lake, a maar lake on St. Michael Island, to determine if a full-glacial eolian record could be found in that region. Particle size and geochemical data indicate that the mineral fraction of the lake sediments is not derived from the local basalt and is probably eolian. Silt deposition took place from at least the latter part of the mid-Wisconsin interstadial period through the Holocene, based on radiocarbon dating. Based on the locations of likely loess sources, eolian silt in western Alaska was probably deflated by northeasterly winds from glaciofluvial sediments. If last-glacial winds that deposited loess were indeed from the northeast, this reconstruction is in conflict with a model-derived reconstruction of paleowinds in Alaska. Mass accumulation rates in Zagoskin Lake were higher during the Pleistocene than during the Holocene. In addition, more eolian sediment is recorded in the lake sediments than as loess on the adjacent landscape. The thinner loess record on land may be due to the sparse, herb tundra vegetation that dominated the landscape in full-glacial time. Herb tundra would have been an inefficient loess trap compared to forest or even shrub tundra due to its low roughness height. The lack of abundant, full-glacial, eolian silt deposition in the loess stratigraphic record of central Alaska may be due, therefore, to a mimimal ability of the landscape to trap loess, rather than a lack of available eolian sediment.
To assess the resource utilization associated with sepsis syndrome in academic medical centers.
Prospective cohort study.
Eight academic, tertiary-care centers.
Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges.
The mean LOS for patients with sepsis was 27.7 ± 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 ± 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 ± 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community-acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post-onset LOS and 12 correlates of total charges were identified.
These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions.
The purpose of the book is to bring together current knowledge about injury in childhood. While there are many books, and a large literature, which address the epidemiology of childhood injury, and textbooks to which doctors can refer when in need of guidance about management of injuries, we believe there has not yet been a book which brings together the science of injury responses and injury management in relation to children.
We have asked our contributors to review experimental and empirical data which influence the rational management of injury in childhood. Because management of injury in its widest sense has to relate to the organisation of pre-hospital services and emergency rooms, and because the needs of children are different to those of adults, we have also included material on organisational issues, and on the management of families when a child cannot be saved. We all start, unashamedly, from the assumption that knowledge acquired in adults cannot readily be extrapolated to the young.
There is no doubt that in recent years there has been a huge advance in our knowledge of injuries in childhood, although publication of this work is scattered across a wide variety of journals and clinical disciplines as can be seen from the reference lists in all the chapters. Other trends have been in evidence as well. Advanced life support courses have become established, both for trauma and specifically for paediatrics.