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Melting at the base of the Antarctic Ice Sheet influences ice dynamics and our ability to recover ancient climatic records from deep ice cores. Basal melt rates are affected by geothermal flux, one of the least constrained properties of the Antarctic continent. Estimates of Antarctic geothermal flux are typically regional in nature, derived from geological, magnetic or seismic data, or from sparse point measurements at ice core sites. We analyse ice-penetrating radar data upstream of South Pole revealing a ~100 km long and 50 km wide area where internal ice sheet layers converge with the bed. Ice sheet modelling shows that this englacial layer configuration requires basal melting of up to 6 ± 1 mm a -1 and a geothermal flux of 120 ± 20 mW m -2 , more than double the values expected for this cratonic sector of East Antarctica. We suggest high heat producing Precambrian basement rocks and hydrothermal circulation along a major fault system cause this anomaly. We conclude that local geothermal flux anomalies could be more widespread in East Antarctica. Assessing their influence on subglacial hydrology and ice sheet dynamics requires new detailed geophysical observations, especially in candidate areas for deep ice core drilling and at the onset of major ice streams.

Airborne gravimetry from a helicopter has been a feasible tool since the 1990s, with gravimeters mounted on a gyro-stabilised platform. In contrast to fixed-wing aircrafts, the helicopter allows for a higher spatial resolution, since it can move slower and closer to the ground. In August 2016, a strapdown gravimetry test was carried out over the Jakobshavn Glacier in Greenland. To our knowledge, this was the first time that a strapdown system was used in a helicopter. The strapdown configuration is appealing because it is easily installed and requires no operation during flight. While providing additional information over the thickest part of the glacier, the survey was designed to assess repeatability both within the survey and with respect to profiles flown previously using a gyro-stabilised gravimeter. The system's ability to fly at an altitude following the terrain, i.e., draped flying, was also tested. The accuracy of the gravity profiles was estimated to 2 mGal and a method for inferring the spatial resolution was investigated, yielding a half-wavelength spatial resolution of 4.5 km at normal cruise speed.

Viral hemorrhagic septicemia virus (VHSV), a rhabdovirus infecting teleost fish, has repeatedly crossed the boundary from marine fish species to freshwater cultured rainbow trout. These naturally replicated cross-species transmission events permit the study of general and repeatable evolutionary events occurring in connection with viral emergence in a novel host species. The purpose of the present study was to investigate the adaptive molecular evolution of the VHSV glycoprotein, one of the key virus proteins involved in viral emergence, following emergence from marine species into freshwater cultured rainbow trout. A comprehensive phylogenetic reconstruction of the complete coding region of the VHSV glycoprotein was conducted, and adaptive molecular evolution was investigated using a maximum likelihood approach to compare different codon substitution models allowing for heterogeneous substitution rate ratios among amino acid sites. Evidence of positive selection was detected at six amino acid sites of the VHSV glycoprotein, within the signal peptide, the confirmation-dependent major neutralizing epitope, and the intracellular tail. Evidence of positive selection was found exclusively in rainbow trout-adapted virus isolates, and amino acid combinations found at the six sites under positive selection pressure differentiated rainbow trout- from non-rainbow trout-adapted isolates. Furthermore, four adaptive sites revealed signs of recurring identical changes across phylogenetic groups of rainbow trout-adapted isolates, suggesting that repeated VHSV emergence in freshwater cultured rainbow trout was established through convergent routes of evolution that are associated with immune escape. IMPORTANCE This study is the first to demonstrate that VHSV emergence from marine species into freshwater cultured rainbow trout has been accompanied by bursts of adaptive evolution in the VHSV glycoprotein. Furthermore, repeated detection of the same adaptive amino acid sites across phylogenetic groups of rainbow trout-adapted isolates indicates that adaptation to rainbow trout was established through parallel evolution. In addition, signals of convergent evolution toward the maintenance of genetic variation were detected in the conformation-dependent neutralizing epitope or in close proximity to disulfide bonds involved in the structural conformation of the neutralizing epitope, indicating adaptation to immune response-related genetic variation across freshwater cultured rainbow trout., (Copyright © 2018 American Society for Microbiology.)

Introduction: The worldwide use of rail transport has increased, and the train speeds are escalating. Concurrently, the number of train disasters has been amplified globally. Consequently, railway safety has become an important issue for the future. High-velocity crashes increase the risk for injuries and mortality; nevertheless, there are relatively few studies on high-speed train crashes and the influencing factors on travelers' injuries occurring in the crash phase. The aim of this study was to investigate the fatal and non-fatal injuries and the main interacting factors that contributed to the injury process in the crash phase of the 2013 high-velocity train crash that occurred at Angrois, outside Santiago de Compostela, Spain., Methods: Hospital records (n=157) of all the injured who were admitted to the six hospitals in the region were reviewed and compiled by descriptive statistics. The instant fatalities (n=63) were collected on site. Influencing crash factors were observed on the crash site, by carriage inspections, and by reviewing official reports concerning the approximated train speed., Results: The main interacting factors that contributed in the injury process in the crash phase were, among other things, the train speed, the design of the concrete structure of the curve, the robustness of the carriage exterior, and the interior environment of the carriages. Of the 222 people on board (218 passengers and four crew), 99% (n=220) were fatally or non-fatally injured in the crash. Thirty-three percent (n=72) suffered fatal injuries, of which 88% (n=63) died at the crash site and 13% (n=9) at the hospital. Twenty-one percent (n=32) of those admitted to hospital suffered multi-trauma (ie, extensive, severe, and/or critical injuries). The head, face, and neck sustained 42% (n=123) of the injuries followed by the trunk (chest, abdomen, and pelvis; n=92; 32%). Fractures were the most frequent (n=200; 69%) injury., Conclusion: A mass-casualty incident with an extensive amount of fatal, severe, and critical injuries is most probable with a high-velocity train; this presents prehospital challenges. This finding draws attention to the importance of more robust carriage exteriors and injury minimizing designs of both railway carriages and the surrounding environment to reduce injuries and fatalities in future high-speed crashes.

An airborne gravimeter is one of the most important tools for gravity data collection over large areas with mGal accuracy and a spatial resolution of several kilometers. In August 2012, a flight test was carried out to determine the feasibility and to assess the accuracy of the new Chinese SGA-WZ strapdown airborne gravimeter in Greenland, in an area with good gravity coverage from earlier marine and airborne surveys. An overview of this new system SGA-WZ is given, including system design, sensor performance and data processing. The processing of the SGA-WZ includes a 160 s length finite impulse response filter, corresponding to a spatial resolution of 6 km. For the primary repeated line, a mean r.m.s. deviation of the differences was less than 1.5 mGal, with the error estimate confirmed from ground truth data. This implies that the SGA-WZ could meet standard geophysical survey requirements at the 1 mGal level.

Survivors' experiences of media at traumatic events, is still a limited research area. The aim of this study is to explore survivors' experiences of interacting with journalists and media coverage, including their experiences of being portrayed in the media, following two Swedish train crashes. Qualitative interviews were conducted with passengers from two train crashes in Sweden. A qualitative content analysis generated meaning units, subcategories, and categories. Survivors experienced interacting with journalists mainly in three ways: harmful, inconsequential, and helpful. Media content and personal media exposure was experienced in a similar way: uncomfortable, insignificant, and useful. Journalists and media coverage have a large impact on survivors' experiences following a traumatic event. It is important that emergency responders, such as ambulance nurses, are aware of how victims are affected by journalists' presence and the media coverage that follows so that negative outcomes can be reduced and the positive can be enhanced. The present study also shows that media coverage in the long term can become important pieces of information for the victim in order to understand and process the traumatic event., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We combined an ensemble of satellite altimetry, interferometry, and gravimetry data sets using common geographical regions, time intervals, and models of surface mass balance and glacial isostatic adjustment to estimate the mass balance of Earth's polar ice sheets. We find that there is good agreement between different satellite methods--especially in Greenland and West Antarctica--and that combining satellite data sets leads to greater certainty. Between 1992 and 2011, the ice sheets of Greenland, East Antarctica, West Antarctica, and the Antarctic Peninsula changed in mass by -142 ± 49, +14 ± 43, -65 ± 26, and -20 ± 14 gigatonnes year(-1), respectively. Since 1992, the polar ice sheets have contributed, on average, 0.59 ± 0.20 millimeter year(-1) to the rate of global sea-level rise.

The Greenland GPS Network (GNET) uses the Global Positioning System (GPS) to measure the displacement of bedrock exposed near the margins of the Greenland ice sheet. The entire network is uplifting in response to past and present-day changes in ice mass. Crustal displacement is largely accounted for by an annual oscillation superimposed on a sustained trend. The oscillation is driven by earth's elastic response to seasonal variations in ice mass and air mass (i.e., atmospheric pressure). Observed vertical velocities are higher and often much higher than predicted rates of postglacial rebound (PGR), implying that uplift is usually dominated by the solid earth's instantaneous elastic response to contemporary losses in ice mass rather than PGR. Superimposed on longer-term trends, an anomalous 'pulse' of uplift accumulated at many GNET stations during an approximate six-month period in 2010. This anomalous uplift is spatially correlated with the 2010 melting day anomaly.

Introduction: Globally, railway transport is increasing steadily. Despite the adoption of diverse safety systems, major railway incidents continue to occur. Higher speeds and increased passenger traffic are factors that influence the risk of mass-casualty incidents and make railway crashes a reality that merits extensive planning and training., Methods: Data on railway disasters were obtained from the Centre for Research on the Epidemiology of Disasters (CRED), which maintains the Emergency Events Database (EM-DAT). This descriptive study consists of 529 railway disasters (≥10 killed and/or ≥100 non- fatally injured) from 1910 through 2009., Results: The number of railway disasters, people killed, and non-fatally injured, has increased throughout the last hundred years-particularly during the last four decades (1970-2009), when 88% of all disasters occurred. In the mid-20th century, a shift occurred, resulting in more people being non-fatally injured than fatally injured. During 1970-2009, 74% of all railway disasters occurred in Asia, Africa, and South and Central America, combined. The remaining 26% occurred in Europe, North America, and Oceania, combined. Since 1980, railway disasters have increased, especially in Asia and Africa, while Europe has had a decrease in railway disasters. The number killed per disaster (1970-2009) was highest in Africa (n = 55), followed by South and Central America (n = 47), and Asia (n = 44). The rate was lowest in North America (n = 10) and Europe (n = 29). On average, the number of non-fatal injuries per disaster was two to three times the number of fatalities, however, in the African countries (except South Africa) the relation was closer to 1:1, which correlates to the relation found in more developed countries during the mid-20th century. The total losses (non-fatally and fatally injured) per disaster has shown a slight decreasing trend., Conclusions: Despite extensive crash avoidance and injury reduction safety systems, railway crashes occur on all continents, indicating that this type of incident must be accounted for in disaster planning and training. Better developed safety, crashworthiness, and rescue resources in North America and Europe may be factors explaining why the number of crashes and losses has stabilized and why the average number of people killed per disaster is lowest on these continents.

Rarely described are people's lived experiences from severe injury events such as train crashes. The number of train crashes named disasters with ≥10 killed and/or ≥100 nonfatally injured grows globally and the trend shows that more people survive these disasters today than did so in the past. This results in an increased number of survivors needing care. The aim of the study was to explore survivors' experiences from a train crash. Narrative interviews were performed with 14 passengers 4 years after a train crash event. Qualitative content analysis was used to analyse the interviews. Experiences were captured in three main themes: (1) Living in the mode of existential threat describes how the survivors first lost control, then were thrown into a state of unimaginable chaos as they faced death. (2) Dealing with the unthinkable described how survivors restored control, the central role of others, and the importance of reconstructing the event to move forward in their processing. (3) Having cheated death shows how some became shackled by their history, whereas others overcame the haunting of unforgettable memories. Furthermore, the result shows how all experienced a second chance in life. Experiencing a train crash meant that the passengers experienced severe vulnerability and a threat to life and interdependence turned out to play a crucial role. Focusing on helping other passengers on site was one way to regain the loss of control and kept the chaos at bay. Family, friends, and fellow passengers turned out to be extremely important during the recovery process why such closeness should be promoted and facilitated.

This study presents a new computer program for assessing the effects of different factors and sequencing strategies on de novo sequence assembly. The program uses reads from actual sequencing studies or from simulations with a reference genome that may also be real or simulated. The simulated reads can be created with our read simulator. They can be of differing length and coverage, consist of paired reads with varying distance, and include sequencing errors such as color space miscalls to imitate SOLiD data. The simulated or real reads are mapped to their reference genome and our assembly simulator is then used to obtain optimal assemblies that are limited only by the distribution of repeats. By way of this mapping, the assembly simulator determines which contigs are theoretically possible, or conversely (and perhaps more importantly), which are not. We illustrate the application and utility of our new simulation tools with several experiments that test the effects of genome complexity (repeats), read length and coverage, word size in De Bruijn graph assembly, and alternative sequencing strategies (e.g., BAC pooling) on sequence assemblies. These experiments highlight just some of the uses of our simulators in the experimental design of sequencing projects and in the further development of assembly algorithms.

This is a descriptive study of the medical responses to the bombings by terrorists in Madrid on 11 March 2004. The nature of the event, the human damage, and the responses are described. It describes the: (1) nature and operations associated with the alarm; (2) assignment of responding units and personnel; (3) establishment and operations of casualty collection points; (4) medical transport and distribution of injured victims; (5) prioritization and command; (6) hospital care; (7) psychosocial care; (8) identification of the dead; and (9) police investigation and actions. Each of these descriptions is discussed in terms of what currently is known and the implications for future planning, preparedness, and response.

Background: Time-structured genetic samples are a valuable source of information in population genetics because they provide several correlated observations of the underlying evolutionary processes. In this paper we study basic properties of the genetic variation in time-structured samples as reflected in the genealogies relating individuals and the number of segregating sites observed. Our emphasis is on "measurably evolving populations" i.e. populations from which it is possible to obtain time-structured samples that span a significant interval of evolutionary time., Results: We use results from the coalescent process to derive properties of time-structured samples. In the first section we extend existing results to attain measures on coalescent trees relating time-structured samples. These include the expected time to a most recent common ancestor, the expected total branch length and the expected length of branches subtending only ancient individuals. The effect of different sampling schemes on the latter measure is studied. In the second section we study the special case where the full sample consists of a group of contemporary extant samples and a group of contemporary ancient samples. As regards this case, we present results and applications concerning the probability distribution of the number of segregating sites where a mutation is unique to the ancient individuals and the number of segregating sites where a mutation is shared between ancient and extant individuals., Conclusion: The methodology and results presented here is of use to the design and interpretation of ancient DNA experiments. Furthermore, the results may be useful in further development of statistical tests of e.g. population dynamics and selection, which include temporal information.

Here we present a model of nucleotide substitution in protein-coding regions that also encode the formation of conserved RNA structures. In such regions, apparent evolutionary context dependencies exist, both between nucleotides occupying the same codon and between nucleotides forming a base pair in the RNA structure. The overlap of these fundamental dependencies is sufficient to cause "contagious" context dependencies which cascade across many nucleotide sites. Such large-scale dependencies challenge the use of traditional phylogenetic models in evolutionary inference because they explicitly assume evolutionary independence between short nucleotide tuples. In our model we address this by replacing context dependencies within codons by annotation-specific heterogeneity in the substitution process. Through a general procedure, we fragment the alignment into sets of short nucleotide tuples based on both the protein coding and the structural annotation. These individual tuples are assumed to evolve independently, and the different tuple sets are assigned different annotation-specific substitution models shared between their members. This allows us to build a composite model of the substitution process from components of traditional phylogenetic models. We applied this to a data set of full-genome sequences from the hepatitis C virus where five RNA structures are mapped within the coding region. This allowed us to partition the effects of selection on different structural elements and to test various hypotheses concerning the relation of these effects. Of particular interest, we found evidence of a functional role of loop and bulge regions, as these were shown to evolve according to a different and more constrained selective regime than the nonpairing regions outside the RNA structures. Other potential applications of the model include comparative RNA structure prediction in coding regions and RNA virus phylogenetics.

Existing computational methods for RNA secondary-structure prediction tacitly assume RNA to only encode functional RNA structures. However, experimental studies have revealed that some RNA sequences, e.g. compact viral genomes, can simultaneously encode functional RNA structures as well as proteins, and evidence is accumulating that this phenomenon may also be found in Eukaryotes. We here present the first comparative method, called RNA-DECODER, which explicitly takes the known protein-coding context of an RNA-sequence alignment into account in order to predict evolutionarily conserved secondary-structure elements, which may span both coding and non-coding regions. RNA-DECODER employs a stochastic context-free grammar together with a set of carefully devised phylogenetic substitution-models, which can disentangle and evaluate the different kinds of overlapping evolutionary constraints which arise. We show that RNA-DECODER's parameters can be automatically trained to successfully fold known secondary structures within the HCV genome. We scan the genomes of HCV and polio virus for conserved secondary-structure elements, and analyze performance as a function of available evolutionary information. On known secondary structures, RNA-DECODER shows a sensitivity similar to the programs MFOLD, PFOLD and RNAALIFOLD. When scanning the entire genomes of HCV and polio virus for structure elements, RNA-DECODER's results indicate a markedly higher specificity than MFOLD, PFOLD and RNAALIFOLD.

Viral haemorrhagic septicaemia (VHS) caused by the rhabdovirus VHSV is economically the most important viral disease in European rainbow trout farming. Until 1989, this virus was mainly isolated from freshwater salmonids but in the last decade, it has also been isolated from an increasing number of free-living marine fish species. To study the genetic evolution of VHSV, the entire G gene from 74 isolates was analysed. VHSV from wild marine species caught in the Baltic Sea, Skagerrak, Kattegat, North Sea, and English Channel and European freshwater isolates, appeared to share a recent common ancestor. Based on the estimated nucleotide substitution rate, the ancestor of the European fresh water isolates was dated some 50 years ago. This finding fits with the initial reports in the 1950s on clinical observations of VHS in Danish freshwater rainbow trout farms. The study also indicates that European marine VHSV and the North American marine line separated approx. 500 years ago. The codon substitution rate among the freshwater VHSV isolates was found to be 2.5 times faster than among marine isolates. The data support the hypothesis of the marine environment being the original reservoir of VHSV and that the change in host range (to include rainbow trout) may have occurred several times. Virus from the marine environment will therefore continue to represent a threat to the trout aquaculture industry.

The estimation of evolutionary rates from serially sampled sequences has recently been the focus of several studies. In this paper, we extend these analyzes to allow the estimation of a joint rate of substitution, omega, from several evolving populations from which serial samples are drawn. In the case of viruses evolving in different hosts, therapy may halt replication and therefore the accumulation of substitutions in the population. In such cases, it may be that only a proportion, p, of subjects are nonresponders who have viral populations that continue to evolve. We develop two likelihood-based procedures to jointly estimate p and omega, and empirical Bayes' tests of whether an individual should be classified as a responder or nonresponder. An example data set comprising HIV-1 partial envelope sequences from six patients on highly active antiretroviral therapy is analyzed.

Parasites sometimes expand their host range by acquiring a new host species. After a host change event, the selective regime acting on a given parasite gene may change as a result of host-specific adaptive alterations of protein functionality or host-specific immune-mediated selection. We present a codon-based model that attempts to include these effects by allowing the position-specific substitution process to change in conjunction with a host change event. Following maximum-likelihood parameter estimation, we employ an empirical Bayesian procedure to identify candidate sites potentially involved in host-specific adaptation. We discuss the applicability of the model to the more general problem of ascertaining whether the selective regime differs in two groups of related organisms. The utility of the model is illustrated on a data set of nucleoprotein sequences from the influenza A virus obtained from avian and human hosts.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a recently emerged pathogen. Two PRRSV genotypes exist, North American and European, which are only 55-70% identical at the nucleotide level. Previous studies have shown high nucleotide diversity in the North American genotype and low nucleotide diversity in the European genotype. Here, we analyzed the ORF5 and ORF7 genes for a large number of new European type PRRSV isolates in conjunction with existing database sequences. This new analysis showed that contrary to previous assumptions, genetic diversity is at least as high in the European genotype as in the North American genotype. Furthermore, we showed that genetic diversity of European type PRRSV has a marked geographical pattern, with exceptionally high genetic diversity among Italian sequences. The geographical pattern of diversity in relation to the epidemiology of PRRSV in Europe is discussed. Discrepancies between ORF5- and ORF7-based genealogies were observed, and further analysis of the data set confirmed the presence of recombination. We were therefore able to report the first observation of recombination in wild-type isolates of European genotype PRRSV.

Tobias Island, discovered in 1993 by the German research vessel RV Polarstern, is a system of low-lying banks and shoals hidden in sea ice 70 km off the northeastern coast of Greenland. Here we use satellite radar interferometry and airborne laser scanning to show that this island is 2 km long and 35 m high --- much larger than was originally reported. We have also been able to pinpoint the exact location of a stable area where a new group of small islands may be hidden. This demonstrates that satellite radar interferometry is an effective tool for finding ice-covered islands as well as for mapping them.

The disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) emerged independently and almost simultaneously in Europe (1990) and North America (1987). The original reservoir of the virus and the date it entered the pig populations is not known. In this study, we demonstrate an accurate molecular clock for the European PRRSV ORF 3 gene, place the root in the genealogy, estimate the rate of nucleotide substitution, and date the most recent common viral ancestor of the data set to 1979; more than 10 years before the onset of the European epidemic. Based on these findings, we conclude that PRRSV virus most likely entered the pig population some time before the epidemic emergence of the virus, and hence, that emergence of European-type PRRSV is not the result of a recent species transmission event. Together, our results show that ORF3 sequencing is a valuable epidemiologic tool for examining the emergence and spread of PRRSV in Europe. As such, the panel of well-characterized and highly divergent ORF3 sequences described in this study provides a reference point for future molecular epidemiologic studies., (Copyright 2001 Academic Press.)

Genetic relationships of 50 SAT-1 type foot-and-mouth disease viruses were determined by phylogenetic analysis of an homologous 417 nucleotide region encoding the C-terminal half of the VP1 gene and part of the 2A segment. Viruses obtained from persistently-infected African buffalo populations were selected in order to assess the regional genetic variation within the host species and compared with ten viruses recovered from recent and historical cases of clinical infection. Phylogenetic reconstructions identified three independently evolving buffalo virus lineages within southern Africa, that correspond with the following discrete geographic localities: (1) South Africa and southern Zimbabwe, (2) Namibia, Botswana and western Zimbabwe, and (3) Zambia, Malawi and northern Zimbabwe. This strict geographic grouping of viruses derived from buffalo was shown to be useful for determining the origin of recent SAT-1 epizootics in livestock. The percentage of conserved amino acid sites across the 50 SAT-1 viruses compared in this study was 50%. Most mutations were clustered within three discrete hypervariable regions, which coincide with the immunogenic G-H loop, H-1 loop and C-terminus region of the protein. Despite the high levels of variation within the primary sequence, secondary structural features appear to be conserved.

It is frequently true that molecular sequences do not evolve in a strictly clocklike manner. Instead, substitution rate may vary for a number of reasons, including changes in selection pressure and effective population size, as well as changes in mean generation time. Here we present two new methods for estimating stepwise changes in substitution rates when serially sampled molecular sequences are available. These methods are based on multiple rates with dated tips (MRDT) models and allow different rates to be estimated for different intervals of time. These intervals may correspond to the sampling intervals or to a priori--defined intervals that are not coincident with the times the serial samples are obtained. Two methods for obtaining estimates of multiple rates are described. The first is an extension of the phylogeny-based maximum-likelihood estimation procedure introduced by Rambaut. The second is a new parameterization of the pairwise distance least-squares procedure used by Drummond and Rodrigo. The utility of these methods is demonstrated on a genealogy of HIV sequences obtained at five different sampling times from a single patient over a period of 34 months.

A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequenced and compared with the parental strain of the vaccine virus (VR2332). This revealed five mutations that had occurred independently in all three vaccine-derived field isolates, indicating strong parallel selective pressure on these positions in the vaccine virus when used in swine herds. Two of these parallel mutations were direct reversions to the parental VR2332 sequence and were situated in a papain-like cysteine protease domain and in the helicase domain. The remaining parallel mutations might be seen as second-site compensatory mutations for one or more of the mutations that accumulated in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change during the time period studied. The implications of these findings for PRRS vaccine attenuation and reversion are discussed.

At the end of history's bloodiest century and the outset of a new millennium, we have an opportunity to fulfil one of humanity's oldest dreams: making the world largely free of war. Global changes make this goal achievable. Nuclear weapons have shown the folly of war. For the first time, there is no war and no immediate prospect of war among the main military powers. For the first time, many proven measures to prevent armed conflict, distilled in the crucible of this century's wars, are available. If systematically applied, these measures can sharply decrease the frequency and violence of war, genocide, and other forms of deadly conflict. To seize the opportunity, nations should adopt a comprehensive programme to reduce conventional armaments and armed conflict. This programme will complement and strengthen efforts to eliminate nuclear arms. To assure its ongoing worldwide implementation, the conventional reduction programme should be placed in a treaty framework. We propose a four-phased process, with three treaties, each lasting five to ten years, to lay the groundwork for the fourth treaty, which will establish a permanent international security system. The main objectives of the treaties are to achieve: 1. A verified commitment to provide full transparency on conventional armed forces and military spending, not to increase forces during negotiations on arms reductions, and to increase the resources allocated to multilateral conflict prevention and peacekeeping. 2. Substantial worldwide cuts in national armed forces and military spending and further strengthening of United Nations and regional peacekeeping and peace-enforcement capabilities. 3. A trial of a watershed commitment by participating nations, including the major powers, not to deploy their armed forces beyond national borders except in a multilateral action under UN or regional auspices. 4. A permanent transfer to the UN and regional security organizations of the authority and capability for armed intervention to prevent or end war, accompanied by further substantial cuts in national armed forces and increases in UN and regional forces. This programme offers many valuable features: a global framework for conventional forces that parallels the nuclear Non-Proliferation Treaty; a verified no-increase commitment for national armed forces based on full data exchange; a commitment to undertake prescribed confidence-building measures, including limits on force activities and deployments; a commitment to a specified plan for increased funding of UN and regional peacekeeping capabilities; a commitment to strengthen international legal institutions; and after a trial period, a lasting commitment by each participant not to unilaterally deploy its armed forces beyond its borders, but instead to give the responsibility for peacekeeping and peace enforcement to international institutions. This programme of phased steps to reduce armed forces and strengthen peacekeeping institutions will make war rare. It will foster the spread of zones of peace like those in North America and Western Europe where, after centuries of violence, international and civil war have given way to the peaceful settlement of disputes.

Objective: Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs., Research Design and Methods: Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal, with a mean follow-up of 3.7 years., Results: Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI]) 2.2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous PO2 0.8 (0.7-0.9), 20 kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups. Unrelated to foot ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education, joint mobility, hallux blood pressure, and other foot deformities., Conclusions: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.

Objective: To assess the relationship between diabetes characteristics, medical history, foot deformity, sensory neuropathy, and plantar foot pressure., Research Design and Methods: There were 517 subjects from a cohort of diabetic veterans enrolled in a prospective study of risk factors for foot complications who contributed 1,017 limbs for study. We interviewed subjects to collect data on demographics, diabetes characteristics, and medical history. A research nurse practitioner performed a directed physical exam of the lower extremities, assessing foot deformities and including quantitative sensory testing with a 5.07 monofilament. In-shoe foot-pressure measurements were obtained with F-scan insoles on subjects wearing their own footwear while walking 10 m at their usual pace., Results: In univariate analyses, significant associations were seen between at least one measure of plantar pressure and body mass, sex, race, age, insulin use, certain foot deformities, plantar callus, and sensory neuropathy. Diabetes duration, HbA1c, and history of foot ulcer or amputation were unrelated to plantar pressure. In multiple regression analyses, body mass measured as log (weight), insulin use, white race, male sex, plantar callus, and diabetes duration were significantly related to certain pressures. Foot deformities were related primarily to forefoot pressures. With high pressure at two or more sites defined as the outcome, only body mass remained statistically significant as a predictor of this outcome in a backwards elimination logistic regression model., Conclusions: High in-shoe plantar pressure in diabetic subjects can be predicted in part from readily available clinical characteristics. The mechanisms by which these characteristics may be related to plantar pressure require further study.

Research by our group and others indicates that many amputations of the lower limb occur after foot ulceration in patients with diabetes. It has been proposed that diabetic foot ulcers are mainly caused by repetitive trauma in areas of high plantar pressure during walking. Recent technology permits in-shoe measurement of plantar pressure. We assessed the reliability of the F-Scan in-shoe system for measurement of plantar pressure (Tekscan Inc., Boston, MA) in 51 subjects from a cohort of 977 diabetic veterans enrolled in a prospective study of risk factors for foot ulceration and amputation (the Seattle Diabetic Foot Study). Subjects were tested twice, wearing their own shoes. We used the coefficient of variation (CV) and the intra-class correlation coefficient (ICC) to estimate the reliability of F-Scan measurements of pressure. Peak pressure over the metatarsal heads proved to have the best indices of reliability, with CVs of 0.150 and 0.155, and ICCs of 0.755 and 0.751. Coefficients of variation for the heel, whole foot, and hallux ranged from 0.148 to 0.240, with ICCs ranging from 0.493 to 0.832. By published standards, peak pressures over the metatarsal heads and right hallux met the criteria for excellent reliability. Our ICCs for high pressures under the foot, heel, metatarsal heads, and hallux, and for peak pressures under the heel and left hallux represented fair-to-good reliability. No F-Scan plantar measurements could be judged by these criteria as having poor reliability. This clinical study found that for elderly patients with diabetes who were wearing their own shoes and were tested on two different days with different insoles, the F-Scan insole system was generally reliable for measurements of high pressure and peak pressure.

Objective: To identify risk factors for diabetic lower-extremity peripheral sensory neuropathy prospectively in a cohort of U.S. veterans with diabetes., Research Design and Methods: General medicine clinic outpatients with diabetes were followed prospectively for the development of insensitivity to the 5.07 monofilament on the foot., Results: Of 775 subjects, 388 (50%) had neuropathy at baseline. Of the 387 subjects without neuropathy at baseline, 288 were followed up, and of these, 58 (20%) developed neuropathy. Multivariate logistic regression modeling of prevalent neuropathy controlling for sex and race revealed independent and significant associations with age, duration of diabetes, glycohemoglobin level, height, history of lower-extremity ulceration, callus, and edema; an independent and inverse correlation was noted with ankle-arm index. Risk factors for incident neuropathy in multivariate logistic regression included age, baseline glycohemoglobin level, height, history of ulcer, and CAGE screening instrument alcohol score; current smoking and albumin level were inversely associated with risk., Conclusions: Poorer glycemic control increases the risk of neuropathy and is amenable to intervention. Height and age directly increase risk of neuropathy and may help identify patients at risk. A proportion of neuropathy in diabetic veterans is probably due to or worsened by alcohol ingestion. Neuropathy was less common in current smokers than subjects not currently smoking.

The Endosperm Balance Number (EBN) and the polar-nuclei activation (PNA) hypotheses have been developed to interpret, explain and predict interspecific and interploidy crossabilities in the Solanums and the Gramineae, respectively. Although these two hypotheses evolved independently, they share a number of common features. Assignment of EBNs and 'activation/response values' (AVs/RVs) depend on plumpness, size, and germinability of hybrid seeds. Also, both hypotheses emphasize the importance of a balanced parental genic contribution for the normal development of endosperm. However, in the EBN hypothesis a 2 maternal∶1 paternal EBN ratio is a prerequisite for successful interspecific crossability, while the PNA hypothesis is based on the stimulative strength of the male nuclei to initiate mitotic divisions in the primary endosperm nucleus and is idependent on a 2∶1 ratio between the RV of the polar nuclei and the AV of the male gamete. Differences and similarities betweeen the EBN and PNA hypotheses are summarized and contrasted. It is proposed that EBN and PNA be considered as the same concept.

In an article titled, "Who Shall Live When Not All Can?", James Childress proposes a system for allocating scarce lifesaving medical resources based on random selection procedures. Childress writes of random selection procedures, [They] "cannot be dismissed as a 'non-rational' and 'non-human' ...without an inquiry into the reasons, including human values which might justify it." My thesis is that once we concentrate on determining the rationality of random selection procedures, we will see that Childress's claim that we cannot dismiss such procedures as 'non-rational' is open to question. My claim will be that while both random selection and social worth procedures are rationally defensible systems, random selection procedures easily lead to specific choices that are objectively irrational, apart from the limited perspective of the random selection process itself.

We have described the clinicopathologic findings in two cases of anorectal melanoma, and extracted the salient features from the medical literature. The disease is rare. Melanoma arises from the anal squamous membrane and very often spreads upward through submucosal planes, producing secondary satelites in the rectum. Trauma from defecation, vast lymphatic and venous systems in the anorectal region, and high invasiveness of the tumor cells eviden;ly account for early distant metastases. Histologically, the neoplastic cells often mimic other cancers. Treatment is surgical, with dismal end results.