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Mycoplasma gallisepticum causes disease in poultry and emerged as a novel pathogen in house finches resulting in a mycoplasmal conjunctivitis epidemic across North America after a single successful host jump from poultry to house finches. The rapid spread of the epidemic across eastern North America, causing a decline in host abundance, has been documented. Once established, disease prevalence showed regular seasonal variation: a late summer/early autumn peak, a mid-December minimum, followed by a late winter peak and a breeding season minimum, which requires seasonal reproduction (providing an autumn pulse of naïve hosts) and winter social aggregation as well as partial immunity of recovered birds. Virulence evolved rapidly: in eastern populations it increased once the disease had become endemic. In western North America the established strain was of much lower virulence, but once established also increased in virulence. We show that virulence may evolve in opposite directions depending on selection pressures. A detailed study showed that disease decreased survival and mobility and a high proportion of birds recovered; also that re-observation rates of clinically diseased birds are often different from those of asymptomatic birds; only calculations which include this effect allow an accurate estimate of disease prevalence.
In April 2014, the Cellular Jail, Andaman Islands, was submitted to the UNESCO World Heritage Site Tentative List for India. The image of the colonial jail, depicted on coins, stamps, and first day covers, symbolizes both the suffering and heroic struggle of India's freedom fighters. Considering how international, national, and local state forces have attempted to ‘freeze’ the meaning of the Cellular Jail, this article questions what has been excluded or obscured from collective memory. Furthermore, it explores the relationship between contending political wills and the symbol of the Cellular Jail through a particular focus on recent struggles between Hindu and secular nationalists over its appropriation. By considering the production of the symbol of the Cellular Jail, this article challenges the narratives at the heart of modern nation-building and demonstrates their intrinsic instability.
This article documents some of the forms of sociality engendered by the massive and growing presence of private security guards around Nairobi, Kenya. A focus on violence and the logic of an ideal of the use of violence in critical security studies literature obfuscates these networks in a similar way to idealizations of public space and the public sphere in anthropological literature on private security and residential enclaves. By looking at the close ties guards maintain with their homes in rural areas of Nairobi and the associations they make with people such as hawkers, it becomes clear that their presence in the city is creating new sets of valuations and obligations all the time. These forms of sociality are not galvanized by the threat of violence that the guards evoke; rather, they are engendered alongside and at cross-currents to the idealized, securitized landscape.
Tags are a form of linked data familiar to those of us who use the internet for social media. These pieces of metadata are usually assigned to posts on social media to help users make sense of the content (Golder and Huberman, 2006), in a way that is generally easy to understand and emulate. It is difficult to use a social media platform like Facebook, Twitter or Tumblr and not come across tagging in one form or another. Hashtags can sprout up amongst many important events or moments, like #blacklivesmatter or #yesallwomen. Generic tags that have very little indication of meaning or importance can also be added to statuses for fun, like #ThursdayThoughts. These are some of the most common uses of social tagging, but they are far from the only examples of social tagging being used in online spaces.
Although the developments leading to modern, western fandom vary according to country (Cuntz-Leng and Meintzinger, 2015), it is generally accepted that fandom as we now would recognise it largely came about in the late 1960s to early 1970s, when the original series of Star Trek (1966) was airing. Star Trek has had a varied following over the years and still attracts many kinds of viewers (Frazetti, 2011), but Star Trek was and is a byword for geek culture. The incredible devotion and love many Star Trek fans have for the series has led to conventions, collectables, and works of art. Fanfiction was a popular way for Star Trek fans to share their own interpretations of the show's characters by creating transformative works of fiction. Some of the oldest examples of modern fanfiction were created by the Star Trek fandom (Verba, 2003), and were copied and shared in person. With ease of access to the internet becoming more widespread, much of fandom now takes place in online spaces, made up of internet based communities. In spite of this massive technological shift, fanfiction and fandoms have changed very little. Put simply, fandoms today are online spaces dedicated to fans, many of whom produce content for their particular interests and share it online.
This Review describes the objectives and methodology of the DairyWater project as it aims to aid the Irish dairy processing industry in achieving sustainability as it expands. With the abolition of European milk quotas in March 2015, the Republic of Ireland saw a surge in milk production. The DairyWater project was established in anticipation of this expansion of the Irish dairy sector in order to develop innovative solutions for the efficient management of water consumption, wastewater treatment and the resulting energy use within the country's dairy processing industry. Therefore, the project can be divided into three main thematic areas: dairy wastewater treatment technologies and microbial analysis, water re-use and rainwater harvesting and environmental assessment. In order to ensure the project remains as relevant as possible to the industry, a project advisory board containing key industry stakeholders has been established. To date, a number of large scale studies, using data obtained directly from the Irish dairy industry, have been performed. Additionally, pilot-scale wastewater treatment (intermittently aerated sequencing batch reactor) and tertiary treatment (flow-through pulsed ultraviolet system) technologies have been demonstrated within the project. Further details on selected aspects of the project are discussed in greater detail in the subsequent cluster of research communications.
In this Research Communication we investigate potential correlations between key bacterial groups and nutrient removal efficiency in an Intermittently Aerated Sequencing Batch Reactor (IASBR) treating synthetic dairy processing wastewater. Reactor aeration rates of 0·6 and 0·4 litre per minute (LPM) were applied to an 8 l laboratory scale system and the relative impacts on IASBR microbial community structure and orthophosphate (PO4-P) and ammonium (NH4-N) removal efficiencies compared. Aeration at 0·6 LPM over several sludge retention times (SRTs) resulted in approximately 92% removal efficiencies for both PO4-P and NH4-N. Biomass samples subjected to next-generation sequencing (NGS), 16S rRNA profiling revealed a concomitant enrichment of Polaromonas under 0·6 LPM conditions, up to ~50% relative abundance within the reactor biomass. The subsequent shift in reactor aeration to 0·4 LPM, over a period of 3 SRTs, resulted in markedly reduced nutrient removal efficiencies for PO4-P (50%) and NH4-N (45%). An 85·7% reduction in the genus level relative abundance of Polaromonas was observed under 0·4 LPM aeration conditions over the same period.
OBJECTIVES/SPECIFIC AIMS: Despite aggressive chemotherapy, surgical resection, and radiation therapy, glioblastoma remains almost universally fatal. In a pilot, randomized, and blinded clinical trial, we recently demonstrated that administration of RNA-loaded DC vaccines was associated with significantly improved progression-free and overall survival in patients with glioblastoma (Mitchell et al., Nature, 2015). Furthermore, clinical outcomes correlated with DC migration to vaccine-site draining lymph nodes measured by Indium-111 labeling of RNA-loaded DCs and SPECT/CT imaging. Although these studies demonstrated that tracking DC migration may be an important clinical biomarker for response to DC vaccination, the complexity and regulatory requirements associated with nuclear labelling to track DC migration limits widespread application of this technique. We have therefore developed RNA-loaded magnetic nanoparticles (RNA-NPs) to enhance DC migration to LNs and track that migration with a widely available imaging modality (i.e., MRI). METHODS/STUDY POPULATION: Cationic liposomes were loaded with iron oxide nanoparticles with or without cholesterol. The resulting nanoparticles were complexed with RNA and used to transfect DCs ex vivo. RNA-NP-loaded DsRed+ DCs were then injected intradermally into mice and tracked noninvasively with T2-weighted 11T MRI before excision and quantification with flow cytometry. RESULTS/ANTICIPATED RESULTS: In vitro experiments demonstrate that iron oxide loading does not reduce RNA-NP-mediated transfection of DCs. Additionally, replacement of cationic lipids with cholesterol increased RNA-NP transfection of the DC2.4 cell line and enhanced the T cell stimulatory capacity of treated bone marrow-derived dendritic cells (BMDCs). Compared to electroporation, RNA-NPs enhanced DC migration to lymph nodes and reduced T2 MRI intensity in DC-bearing lymph nodes. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that iron oxide-loaded RNA-NPs enable noninvasive cell tracking with MRI and enhance DC migration to lymph nodes. We have further shown that inclusion of cholesterol in RNA-NPs augments the stimulatory capacity of transfected DCs. Future work will consider effects of RNA-NPs on antitumor immune responses and the utility of MRI-detected DC migration as a biomarker of vaccine efficacy.
Many women experience both vasomotor menopausal symptoms (VMS) and depressed mood at midlife, but little is known regarding the prospective bi-directional relationships between VMS and depressed mood and the role of sleep difficulties in both directions.
A pooled analysis was conducted using data from 21 312 women (median: 50 years, interquartile range 49−51) in eight studies from the InterLACE consortium. The degree of VMS, sleep difficulties, and depressed mood was self-reported and categorised as never, rarely, sometimes, and often (if reporting frequency) or never, mild, moderate, and severe (if reporting severity). Multivariable logistic regression models were used to examine the bi-directional associations adjusted for within-study correlation.
At baseline, the prevalence of VMS (40%, range 13–62%) and depressed mood (26%, 8–41%) varied substantially across studies, and a strong dose-dependent association between VMS and likelihood of depressed mood was found. Over 3 years of follow-up, women with often/severe VMS at baseline were more likely to have subsequent depressed mood compared with those without VMS (odds ratios (OR) 1.56, 1.27–1.92). Women with often/severe depressed mood at baseline were also more likely to have subsequent VMS than those without depressed mood (OR 1.89, 1.47–2.44). With further adjustment for the degree of sleep difficulties at baseline, the OR of having a subsequent depressed mood associated with often/severe VMS was attenuated and no longer significant (OR 1.13, 0.90–1.40). Conversely, often/severe depressed mood remained significantly associated with subsequent VMS (OR 1.80, 1.38–2.34).
Difficulty in sleeping largely explained the relationship between VMS and subsequent depressed mood, but it had little impact on the relationship between depressed mood and subsequent VMS.
Large numbers of new medical devices and diagnostics are developed and health services need to identify which ones offer real advantages. The National Institute for Health and Care Excellence (NICE) has introduced a system for assessing technologies that are often notified by companies, based on claims made for their benefits to patients, the National Health Service, and the environment.
Detailed scrutiny of claims made for the benefits of products and the corresponding evidence, seeking associations between these and the selection of products for full evaluation to produce NICE guidance.
Between 2009 and 2015 a NICE committee considered 169 technologies, of which it selected 74 (44 percent) for full evaluation, based on the claims of benefit and the evidence available. An average of 7.5 claims were made per technology; the total number did not influence selection but presence of studies supporting all the claims (p < .001) or any of the claims (p < .05) had a positive influence, as did claims for quicker patient recovery (p < .001). A greater number of studies to support the claims made selection more likely (p < .001), as did cohort studies (p < .05) and surveys (p < .05) but, unexpectedly, not randomized trials. The Medical Device Directive class had no influence.
This study presents categories of claims that may be useful to those developing new products and to others engaged in health technology assessment. It illustrates the importance of relevant evidence and of having a clear vision of the place of new products in care pathways from an early stage.
Perinatal and later postnatal adversities have been shown to adversely affect socioeconomic trajectories, while enhanced early cognitive abilities improve them. However, little is known about the combined influence of these exposures on social mobility. In this study, we examined if childhood IQ moderated the association between four different types of postnatal adversity (childhood socioeconomic disadvantage, childhood sexual abuse, lifetime psychiatric disorder, and trait neuroticism) and annual earnings at 30–35 years of age in a sample of 88 extremely low birth weight survivors. Our results suggested that higher childhood IQ was associated with greater personal income at age 30–35. Extremely low birth weight survivors who did not face psychological adversities and who had higher childhood IQ reported higher income in adulthood. However, those who faced psychological adversity and had higher childhood IQ generally reported lower income in adulthood. Our findings suggest that cognitive reserve may not protect preterm survivors against the complex web of risk factors affecting their later socioeconomic attainment.
OBJECTIVES/SPECIFIC AIMS: Immune-based therapies hold great promise for treatment of refractory tumors. However, development is limited by a lack of identified immune correlates to vaccination. We recently showed that dendritic cells (DCs) prolong progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma, and that DC migration to site draining lymph nodes robustly correlates with both PFS and OS. While this appears to be a reliable immune correlate, the complexity of routine labeling for PET and SPECT prohibits validation in a large clinical study. We therefore seek to develop a safe, translatable reporter that can be imaged with a widely available imaging modality. METHODS/STUDY POPULATION: The cationic liposome 1,2-doleoyl-3-trimethylammonium-propane (DOTAP) was loaded with MRI-imageable iron oxide nanoparticles (IONPs) with or without the neutral molecules PEG and cholesterol. The resulting nanoparticles were loaded with RNA to form RNA-NPs that were characterized with transmission electron microscopy (TEM) and used to transfect DCs in vitro; 4.7 T MRI was then used to image particles or cells in agarose gel phantoms. RESULTS/ANTICIPATED RESULTS: TEM images of RNA-NPs indicate the presence of IONP-loaded liposomes. In vitro transfection experiments demonstrate that iron oxide does not reduce RNA-NP-mediated transfection of DCs. Additionally, small amounts of either PEG or cholesterol within RNA-NPs increased transfection of DC2.4s and enhanced T-cell priming by bone marrow-derived dendritic cells. A series of 4.7 T MRI images of particles in cells, spleens, and LNs demonstrated quantifiable differences in particle density between groups. DISCUSSION/SIGNIFICANCE OF IMPACT: This data suggests that IONP-loaded RNA-NPs can be imaged with MRI and manipulated to augment DC function. Future work will include in vivo imaging in mice and safety studies to facilitate translation into first-in-human studies. Successful completion of this project would provide a powerful clinical tool to improve and track patient responses to immune therapy.
Introduction: Collaborative Emergency Centres (CECs) provide access to care in rural communities. After hours, registered nurses (RNs) and paramedics work together in the ED with telephone support by an emergency medical services (EMS) physician. The safety of such a model is unknown. Relapse visits are often used as a proxy measure for safety in emergency medicine. The primary outcome of this study is to measure unscheduled relapses to emergency care. Methods: The electronic patient care record (ePCR) database was queried for all patients who visited two CECs from April 1, 2012 to April 1, 2013. Abstracted data included demographics, time, acuity score, clinical impression, chief complaint, and disposition. Records were searched for each discharged CEC patient to identify unscheduled relapses to emergency care, defined as presenting back to EMS, CEC, or any other ED within the Health Authority within 48 hours of CEC discharge. Results: There were 894 CEC visits, of which 66 were excluded due to missing data. The dispositions from CEC were: 131/828 (15.8%) transferred to regional ED; 264/828 (31.9%) discharged home; 488/828 (58.9%) discharged with follow up visit booked; and 11/82 (1.2%) left the CEC without being seen. There was 37/828 (4.5%) visits which relapsed back to emergency care, all of whom were discharged from CEC or left without being seen: 3/828 (0.4%) relapsed back to EMS (two taken to regional ED and one to CEC); 16/828 (1.9%) relapsed to regional ED (by walking-in); and 18/828 (2.2%) had a relapse to the CEC (walk-in). 516/828 (62.3%) CEC visits were resolved in a single visit. Conclusion: This study was based on only two of the 7 operating CECs due to accessing paper-based charts for multiple health regions. We also acknowledge the limitations of using relapse as a proxy for safety, and that low volumes and acuity will make detection of adverse events challenging. Albeit a proxy measure, the rate of patients who relapse to emergency care was under 5% in this case series of two CECs. Most patients had their concern resolved in a single visit to a CEC. Further research is underway to determine the effectiveness, optimal utilization and safety of this collaborative model of rural emergency care.
In 2015, frustrated by the slow pace of negotiations in the International Maritime Organisation, the EU issued Regulation 2015/757 on the monitoring, reporting, and verification of carbon dioxide emissions from maritime transport. Echoing the controversial Aviation Directive, the Regulation is intended to support a unilateral market-based measure, and includes emissions from outside EU territory. This raises the question whether, according to international law, the EU has jurisdiction to regulate such ‘extraterritorial’ circumstances. In exploring the appropriate jurisdictional bases, we argue that neither the Law of the Sea Convention, nor world trade law definitively decide this issue. We therefore devote more detailed attention to the customary international law of State jurisdiction supplementing these regimes. We seek to build on the existing analysis by examining climate change as a ‘common concern of mankind’. We argue that this emerging concept has distinct legal implications that can and should be accommodated within the interest-balancing exercise underlying the jurisdictional analysis.
In 1892 the celebrated physicist and chemist William Crookes commented on the existence of “an almost infinite range of ethereal vibrations or electrical rays,” which he believed could revolutionize telegraphic communications (174). A few years later, and aided by Crookes's experiments with vacuums, the German physicist Wilhelm Röntgen successfully produced X-rays, a hitherto unrecorded form of electromagnetic radiation, which he tantalizingly described as “a new kind of invisible light” (Röntgen 413; Warner 256). Crookes was quick to speculate as to “the possibility of links between roentgen rays and the cerebral ganglia,” that an undiscovered organ in the brain might be “capable of transmitting and receiving . . . electrical rays” (Lyons 105; Crookes 176). X-rays, he thought, might prove a psychic counterpart to higher wavelength radio waves, allowing the transmission of messages telepathically rather than telegraphically, and even communication with the world of the spirits (Lyons 105). Crookes theorized that the parapsychological was intimately entwined with the findings of contemporary physics, occupying different zones of the same electromagnetic spectrum. An ardent Spiritualist, he believed that the ether, the “impalpable, invisible entity, by which all space is supposed to be filled” and which contained countless “channels of communication” also sustained “ghost-light . . . invisible to the naked eye” and acted as a medium that allowed “ethereal bodies to rise up” (Crookes 174; Warner 253–56). In other words, the matter through which light and electrical signals passed was envisaged as the same substance which allowed the spirits to fluctuate between visible and invisible forms. These links between the electromagnetic field and the occult, endorsed by Crookes and certain other members of his circles such as the Society for Psychical Research, anticipated turn-of-the-century associations between electricity, radiation and ancient Egypt which, through its reputation as the birthplace of magic, was central to Victorian conceptions of the supernatural.
A broad chronological overview of the plagues of the past and the present provides a basis for understanding how they have arisen, how they have affected societies over time, and how humanity has responded to the challenge of each new wave of deadly disease. Many puzzles still surround the plagues of antiquity, although recent techniques such as DNA analysis of skeletal remains are beginning to provide clues as to their causes; it has, for example, now been confirmed that the plague bacillus, Yersinia pestis, was responsible for the ‘Black Death’ of the mid-14th century. Many other infectious diseases or ‘plagues’, such as smallpox, typhus, cholera and influenza, have afflicted human populations over the centuries. As the causes of these diseases have become increasingly well understood, humanity has devised ever more effective means for their control. With the extension of human lifespan that has resulted from such progress, other medical conditions have become increasingly common, notably the neurological disorder, Alzheimer's disease. Although not infectious, this disease has become so prevalent in recent years that it is has been called a ‘21st century plague’. The intrinsic origins of this highly debilitating condition are now being explored intensively by scientists from many different disciplines leading, as with the plagues of the past, to new ideas as to potential strategies for its prevention and treatment.
Most people associate the word ‘plague’ with the ‘Black Death’ of the mid-fourteenth century, which in the space of a few years killed between a third and a half of the population of Europe, Asia and the Middle East – with frightening consequences. However, throughout history there have been many other widespread and devastating outbreaks of disease that have been labelled as plagues. The word ‘plague’ comes from the Latin plaga, meaning a stroke or a wound; the Oxford English Dictionary also defines it as an affliction, calamity or a general name for any malignant diseases ‘with which men or beasts are stricken’. The word is, moreover, now becoming associated with some disorders that are not infectious, but which have increased in prevalence so rapidly that they have been likened to the historic plagues.
One such condition in humans is dementia, which has been called the ‘twenty-first century plague’, and indeed it is perhaps as greatly feared today as the classic plagues were in the past.
Growing interest in the use of CO2 as a feedstock for fuel generation has led to increased interest in solar CO2 electrolysis for renewable fuel generation which has a variety of applications ranging from providing renewable sources for energy-dense carbon fuels, to curbing high-density emissions from power plants, industries and automobiles. The challenges of integrated solar-to-carbon fuel converters, where the photovoltaic (PV) material is immersed in the electrolyte, are well-known: the need for unique PV cell designs; material incompatibility; corrosion; and optical losses. In this paper, a PV-electrolysis system is presented, where a flow-cell electrolyzer is power-matched to a high-performance solar PV module array which has two system design advantages: 1) use of standard PV cells external to the electrolyzer, which allows de-coupling the design, fabrication and operation of the PV system from that of the electrolyzer; and 2) enabling optimization of the PV configuration to maximize power coupling efficiency to the specific electrolyzer Tafel curve, with or without the use of electronic power-conditioning devices. The implemented system resulted in a peak SFE of 6.5%, a competitive solar-to-fuel efficiency (SFE) figure to those reported in literature.
Objectives: The aim of this study was to review 5 years of activity from a new system devised by the National Institute for Health and Care Excellence (NICE), for assessing medical devices and diagnostics aimed at identifying and speeding adoption of technologies with clinical and cost advantages, compared with current practice in the United Kingdom healthcare system.
Methods: All eligible notified technologies were classified using the Food and Drug Administration and Global Medical Device Nomenclature nomenclatures. Decisions about selecting technologies for full assessment to produce NICE recommendations were reviewed, along with the reasons given to companies for not selecting products.
Results: Between 2009 and 2014, 186 technologies were notified (46 percent therapeutic and 54 percent diagnostic). Thirty-nine were judged ineligible (no regulatory approval), and 147 were considered by an independent committee. Of these, eighty (54 percent) were not selected for full assessment, most commonly because of insufficient evidence (86 percent): there were uncertainties specifically about benefits to the health service (54 percent), to patients (39 percent), and about cost (24 percent). The remaining 67 were selected and assessed for Medical Technology guidance (52 percent) (noninferior and/or lower cost consequences than current practice), for Diagnostics guidance (43 percent) or other NICE recommendations about adoption and use. Classifying technologies by two different systems showed no selection bias for any technology type or disease area.
Conclusions: Identifying new or under-used devices and diagnostics with potential benefits and promoting their adoption is important to health services in the United Kingdom and worldwide. This new system offers a means of fostering both uptake and further research. Lack of research data on new products is a major obstacle to evaluation.