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Newsday reporter Patrick Owens' articles [\"Disability Nightmare Isn't Over,\" July 23 and \"Disability Policy Shift Termed Sham,\" July 24] has again brought to light the problems that will be caused by the Reagan administration's continued attack on the Social Security Disability program.

A few years ago we heard about [Charles Wang] buying up the properties and heard different things about his intentions for Oyster Bay. To this day, the only things I can see happening are high cost of living and congestion. Abraham Poznanski has said, \"We would like to get as much housing into the downtown area as possible.\" He seems to think that this would pump money into the local economy. But I wonder if Poznanski ever rode through the streets of Oyster Bay and saw the dozens of houses for sale and the vacant store buildings. We need to get more businesses into town that people want and need. You can only go to so many delis and nail salons. Unfortunately, the current U.S. policy on global warming is one of indifference at a time when our country's production of greenhouse-gas pollution from burning oil, coal and gasoline is increasing. But in coming weeks, U.S. senators will have a chance to vote for decisive action on global warming in the McCain-Lieberman Climate Stewardship Act. Last October, the reasonable and responsible measure secured 43 votes in the Senate, surprising the pundits and building momentum for the upcoming vote on global warming. The Metropolitan Transportation Authority, New York City Transit, Long Island Rail Road, Long Island Bus, Metro-North Commuter Railroad, Staten Island Rapid Transit, New Jersey Transit, Port Authority of New York and New Jersey, Connecticut Department of Transportation, New York City Department of Transportation, and Staten Island Ferry, along with many other services supported by Nassau, Suffolk, Westchester, Rockland and Putnam counties and the City of Long Beach and Town of Huntington, all provide such options. There are many private bus and ferry operators, including New York Waterways, Command Bus Lines in Brooklyn, New York Bus and Liberty Lines Express in the Bronx, along with Green Bus Lines, Jamaica Buses of Queens, Queens Surface and Triboro Coach in Queens and many smaller suburban operators.

To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100–200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. When subjects lie motionless inside scanners without any particular task to perform, their brains show stereotyped patterns of activity across regions known as resting state networks. Each network consists of areas with a common function, such as the ‘motor’ network or the ‘visual’ network. The role of resting state networks is unclear, but these spontaneous activity patterns are altered in disorders including autism, schizophrenia, and Alzheimer’s disease. One puzzling feature of resting state networks is that they seem to last for relatively long times. However, the majority of studies into resting state networks have used fMRI brain scans, in which changes in the level of oxygen in the blood are used as a proxy for the activity of a given brain region. Since changes in blood oxygen occur relatively slowly, the ability of fMRI to detect rapid changes in activity is limited: it is thus possible that the long-lived nature of resting state networks is an artefact of the use of fMRI. Now, Baker et al. have used a different type of brain scan known as an MEG scan to show that the activity of resting state networks is shorter lived than previously thought. MEG scanners measure changes in the magnetic fields generated by electrical currents in the brain, which means that they can detect alterations in brain activity much more rapidly than fMRI. MEG recordings from the brains of nine healthy subjects revealed that individual resting state networks were typically stable for only 100 ms to 200 ms. Moreover, transitions between different networks did not occur randomly; instead, certain networks were much more likely to become active after others. The work of Baker et al. suggests that the resting brain is constantly changing between different patterns of activity, which enables it to respond quickly to any given situation.

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS.

The heterogeneous nature of inflammatory bowel disease (IBD) presents challenges, particularly when choosing therapy. Activation of the NF-κB transcription factor is a highly regulated, dynamic event in IBD pathogenesis. Using a lentivirus approach, NF-κB-regulated luciferase was expressed in patient macrophages, isolated from frozen peripheral blood mononuclear cell samples. Following activation, samples could be segregated into three clusters based on the NF-κB-regulated luciferase response. The ulcerative colitis (UC) samples appeared only in the hypo-responsive Cluster 1, and in Cluster 2. Conversely, Crohn's disease (CD) patients appeared in all Clusters with their percentage being higher in the hyper-responsive Cluster 3. A positive correlation was seen between NF-κB-induced luciferase activity and the concentrations of cytokines released into medium from stimulated macrophages, but not with serum or biopsy cytokine levels. Confocal imaging of lentivirally-expressed p65 activation revealed that a higher proportion of macrophages from CD patients responded to endotoxin lipid A compared to controls. In contrast, cells from UC patients exhibited a shorter duration of NF-κB p65 subunit nuclear localization compared to healthy controls, and CD donors. Analysis of macrophage cytokine responses and patient metadata revealed a strong correlation between CD patients who smoked and hyper-activation of p65. These dynamic assays of NF-κB activation in blood-derived macrophages have the potential to segregate IBD patients into groups with different phenotypes and may therefore help determine response to therapy.

Predicting when a patient with advanced cancer is dying is a challenge and currently no prognostic test is available. We hypothesised that a dying process from cancer is associated with metabolic changes and specifically with changes in volatile organic compounds (VOCs). We analysed urine from patients with lung cancer in the last weeks of life by headspace gas chromatography mass spectrometry. Urine was acidified or alkalinised before analysis. VOC changes in the last weeks of life were identified using univariate, multivariate and linear regression analysis; 12 VOCs increased (11 from the acid dataset, 2 from the alkali dataset) and 25 VOCs decreased (23 from the acid dataset and 3 from the alkali dataset). A Cox Lasso prediction model using 8 VOCs predicted dying with an AUC of 0.77, 0.78 and 0.85 at 30, 20 and 10 days and stratified patients into a low (median 10 days), medium (median 50 days) or high risk of survival. Our data supports the hypothesis there are specific metabolic changes associated with the dying. The VOCs identified are potential biomarkers of dying in lung cancer and could be used as a tool to provide additional prognostic information to inform expert clinician judgement and subsequent decision making.

Materials that demonstrate long-range magnetic order are synonymous with information storage and the electronics industry, with the phenomenon commonly associated with metals, metal alloys or metal oxides and sulfides. A lesser known family of magnetically ordered complexes are the monometallic compounds of highly anisotropic d-block transition metals; the ‘transformation’ from isolated zero-dimensional molecule to ordered, spin-canted, three-dimensional lattice being the result of through-space interactions arising from the combination of large magnetic anisotropy and spin-delocalization from metal to ligand which induces important intermolecular contacts. Here we report the effect of pressure on two such mononuclear rhenium(IV) compounds that exhibit long-range magnetic order under ambient conditions via a spin canting mechanism, with T c controlled by the strength of the intermolecular interactions. As these are determined by intermolecular distance, ‘squeezing’ the molecules closer together generates remarkable enhancements in ordering temperatures, with a linear dependence of T c with pressure. Materials that demonstrate long-range magnetic order are synonymous with information storage. Here, the authors report the effect of pressure on two mononuclear rhenium compounds that exhibit long-range magnetic order under ambient conditions via a spin canting mechanism, where T c is proportional to pressure.

Background: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. Methods: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. Results: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. Conclusions: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.

Protected areas provide major benefits for humans in the form of ecosystem services, but landscape degradation by human activity at their edges may compromise their ecological functioning. Using multiple lines of evidence from 40 years of research in the Serengeti-Mara ecosystem, we find that such edge degradation has effectively “squeezed” wildlife into the core protected area and has altered the ecosystem’s dynamics even within this 40,000-square-kilometer ecosystem. This spatial cascade reduced resilience in the core and was mediated by the movement of grazers, which reduced grass fuel and fires, weakened the capacity of soils to sequester nutrients and carbon, and decreased the responsiveness of primary production to rainfall. Similar effects in other protected ecosystems worldwide may require rethinking of natural resource management outside protected areas.

IntroductionThe increasing use of metabolomic analysis in irritable bowel syndrome (IBS) has led to the emergence of a distinct IBS metabotype enriched in short chain fatty acids (SCFAs). Although SCFAs are essential for gut health, there exists potential for them to exert pro-nociceptive and pro-kinetic effects depending on the colonic environment within which they are produced. Whether a metabotype rich in SCFA simply denotes a phenotype characterised by faster transit, or whether this represents a more severe IBS phenotype is uncertain.MethodsSolid phase microextraction gas chromatography-mass spectrometry was used to examine the faecal headspace of 63 patients with moderate-severe IBS-D (diarrhoeal subtype). The SCFA metabotype was identified by hierarchical clustering - figure 1. Baseline clinical and mechanistic data were compared between the two groups using an independent samples t-test. Clinical metrics including IBS symptom severity (IBS-SSS), abdominal pain and urgency (rating scales 0–100), stool consistency (Bristol Stool Form Scale; BSFS), and stool frequency. Mechanistic metrics included whole gut transit time (WGTT). Pearson correlation was used to detect any relationships between WGTT and symptoms in this cohort.ResultsThe SCFA metabotype was exhibited by 32% of patients. The other metabotype was characterised by a relative deficiency of these metabolites, and a relative excess of ketones, aldehydes, and sulfoxymethanes. Patients with the SCFA metabotype were characterised by higher abdominal pain 67.2 vs 53.1; p<0.01) and urgency scores (72.7 vs 59.0; p<0.05), and greater stool frequency (4.7 vs 3.5 per 24 hours; p<0.05) at baseline. WGTT was significantly faster in those with the SCFA metabotype compared to those without (mean duration 5.3 vs 12.8 hours respectively; p<0.001, 95% CI µ1-µ2 [3.40–11.27]). No significant correlation was observed between WGTT and IBS symptoms.ConclusionThe SCFA metabotype appears to represent a more severe IBS-D phenotype characterised by pain, urgency, rapid transit and high stool frequency. Although it is possible that the enrichment of SCFA in this group could be the product of faster transit, the lack of negative-correlation between WGTT and IBS symptoms suggests that the metabolites are contributing to the generation of the more severe symptom-profile in this group.Abstract O63 Figure 1