HI Clouds Beyond the Galactic Disk

Recent observations in the 21cm line with the Green Bank Telescope have changed our view of the neutral interstellar medium (ISM) in several ways. The new data show that in the inner parts of the Milky Way the disk-halo interface is composed of many discrete HI clouds. The clouds lie in a layer more than one kpc thick and follow Galactic rotation. Their origin and evolution is unknown. In the outer Galaxy, the new data show that the high-velocity cloud Complex H is likely a satellite on a retrograde orbit interacting with some extended component of the Milky Way's ISM. These observations place new constraints on models of the ISM and are directly related to the work of Don Cox and Ron Reynolds.Comment: 8 pages includes 2 figures. To appear in "How Does the Galaxy Work?", eds. E.J. Alfaro, E. Perez, & J. Franco, Kluwer, Proceedings of a Conference held 23-27 June 2003 in Granada, Spai

Overview of Land Use Transport Models

The previous chapters in this Handbook have shown that spatial development, or land use, determines the need for spatial interaction, or transport, but that transport, by the accessibility it provides, also determines spatial development. However, it is difficult to empirically isolate impacts of land use on transport and vice versa because of the multitude of concurrent changes of other factors. This poses a problem if the likely impacts of integrated land-use and transport policies to reduce the demand for travel are to be predicted. There are principally three methods to predict those impacts. The first is to ask people how they would change their location and mobility behaviour if certain factors, such as land use regulations or transport costs, would change ('stated preference'). The second consists of drawing conclusions from observed decision behaviour of people under different conditions on how they would be likely to behave if these factors would change ('revealed preference'). The third method is to simulate human decision behaviour in mathematical models. All three methods have their advantages and disadvantages. Surveys can reveal also subjective factors of location and mobility decisions, however, their respondents can only make conjec-tures about how they would behave in still unknown situations, and the validity of such con

Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

Animal Welfare Considerations: Should Context Matter?

Much consideration of animal welfare issues, as well as the bulk of welfare legislation, is closely related to context, with clear distinction between defined responsibilities towards farm-, laboratory-, companion- and wild animals. It has however been recognised that such distinction leads to inconsistencies, in that it might lead to different welfare management practices for the same rat (for example) as a pet, laboratory animal or pest. We suggest that if legal provisions recognize animals as having moral status, then that implies certain responsibilities towards the animal that cannot be context-dependent. Although we argue the moral responsibility to consider an animal’s welfare is context-independent, we suggest that the requirement to take action (and the form of that action) may alter with context. From a biological perspective, we argue that there exists an obligation to take action to address potential welfare problems only when a challenge exceeds the animal’s adaptive capacity, such that it cannot adequately respond by changes of its behaviour. The obligation to intervene further depends on whether or not there are practical (and economically feasible) options available for mitigation. Beyond this, additional constraints may be posed by anthropocentric aims or objectives, where any suffering may be adjudged avoidable (in theory), but necessary (because of specific human interests). Finally, whatever may be determined necessary or unavoidable by the actual manager or agent himself/herself, such judgement is inevitably subjective and possibly subject to self-interest. Thus any decision must be further evaluated within the context of what is considered by a wider society to be (morally) acceptable or unacceptable

Animal Welfare at the Group Level: More Than the Sum of Individual Welfare?

Currently assessment and management of animal welfare are based on the supposition that welfare status is something experienced identically by each individual animal when exposed to the same conditions. However, many authors argue that individual welfare cannot be seen as an 'objective' state, but is based on the animal's own self-perception; such perception might vary significantly between individuals which appear to be exposed to exactly the same challenges. We argue that this has two implications: (1) actual perceived welfare status of individuals in a population may vary over a wide range even under identical environmental conditions; (2) animals that appear to an external observer to be in better or poorer welfare condition may all in fact perceive their own individual status as the same. This would imply that optimum welfare of a social group might be achieved in situations where individual group members differ markedly in apparent welfare status and perceive their own welfare as being optimal under differing circumstances. Welfare phenotypes may also vary along a continuum between self-regarding and other-regarding behaviour; a variety of situations exist where (social) individuals appear to invest in the welfare of other individuals instead of maximising their own welfare; in such a case it is necessary to re-evaluate individual welfare within the context of a social group and recognise that there may be consequences for the welfare of individuals, of decisions made at the group level or by other group members

Principles of Ecology

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Animal Welfare at the Group Level: More Than the Sum of Individual Welfare?

Currently assessment and management of animal welfare are based on the supposition that welfare status is something experienced identically by each individual animal when exposed to the same conditions. However, many authors argue that individual welfare cannot be seen as an 'objective' state, but is based on the animal's own self-perception; such perception might vary significantly between individuals which appear to be exposed to exactly the same challenges. We argue that this has two implications: (1) actual perceived welfare status of individuals in a population may vary over a wide range even under identical environmental conditions; (2) animals that appear to an external observer to be in better or poorer welfare condition may all in fact perceive their own individual status as the same. This would imply that optimum welfare of a social group might be achieved in situations where individual group members differ markedly in apparent welfare status and perceive their own welfare as being optimal under differing circumstances. Welfare phenotypes may also vary along a continuum between self-regarding and other-regarding behaviour; a variety of situations exist where (social) individuals appear to invest in the welfare of other individuals instead of maximising their own welfare; in such a case it is necessary to re-evaluate individual welfare within the context of a social group and recognise that there may be consequences for the welfare of individuals, of decisions made at the group level or by other group members