Migration towards Bangladesh coastlines projected to increase with sea-level rise through 2100.

To date, projections of human migration induced by sea-level change (SLC) largely suggest large-scale displacement away from vulnerable coastlines. However, results from our model of Bangladesh suggest counterintuitively that people will continue to migrate toward the vulnerable coastline irrespective of the flooding amplified by future SLC under all emissions scenarios until the end of this century. We developed an empirically calibrated agent-based model of household migration decision-making that captures the multi-faceted push, pull and mooring influences on migration at a household scale. We then exposed ~4800 000 simulated migrants to 871 scenarios of projected 21st-century coastal flooding under future emissions pathways. Our model does not predict flooding impacts great enough to drive populations away from coastlines in any of the scenarios. One reason is that while flooding does accelerate a transition from agricultural to non-agricultural income opportunities, livelihood alternatives are most abundant in coastal cities. At the same time, some coastal populations are unable to migrate, as flood losses accumulate and reduce the set of livelihood alternatives (so-called 'trapped' populations). However, even when we increased access to credit, a commonly-proposed policy lever for incentivizing migration in the face of climate risk, we found that the number of immobile agents actually rose. These findings imply that instead of a straightforward relationship between displacement and migration, projections need to consider the multiple constraints on, and preferences for, mobility. Our model demonstrates that decision-makers seeking to affect migration outcomes around SLC would do well to consider individual-level adaptive behaviors and motivations that evolve through time, as well as the potential for unintended behavioral responses.

[Radiation dose in cerebral angiography and flat detector CT applications in neuroradiology]. / Strahlendosis bei zerebraler Angiographie und Flachdetektor-CT-Applikationen in der Neuroradiologie.

Flat detectors (FD) have completely replaced image intensifiers in angiography. Due to this development not only the image quality of 2D digital subtraction angiography series (2-D-DSA) could be improved but also the acquisition of computed tomography (CT)-like cross-sectional images (FD-CT) within the angio suite became feasible. These techniques are now being used in daily clinical routine. Only little information about effective doses of these applications to patients has been published in the literature. We describe the effective patient dose of current applications in the field of angiography and demonstrate strategies to minimize the dose to the patient. In addition, we compare FD-CT applications to standard multislice CT applications.

Event-by-event fluctuations of azimuthal particle anisotropy in Au+Au collisions at square root(sNN) = 200 GeV.

This Letter presents the first measurement of event-by-event fluctuations of the elliptic flow parameter v(2) in Au+Au collisions at square root(s(NN))=200 GeV as a function of collision centrality. The relative nonstatistical fluctuations of the v(2) parameter are found to be approximately 40%. The results, including contributions from event-by-event elliptic flow fluctuations and from azimuthal correlations that are unrelated to the reaction plane (nonflow correlations), establish an upper limit on the magnitude of underlying elliptic flow fluctuations. This limit is consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. These results provide important constraints on models of the initial state and hydrodynamic evolution of relativistic heavy ion collisions.

High transverse momentum triggered correlations over a large pseudorapidity acceptance in Au + Au collisions at square root(s(NN)) = 200 GeV.

A measurement of two-particle correlations with a high transverse momentum trigger particle (p(T)(trig) > 2.5 GeV/c) is presented for Au+Au collisions at square root(s(NN)) = 200 GeV over the uniquely broad longitudinal acceptance of the PHOBOS detector (-4 < Delta eta < 2). A broadening of the away-side azimuthal correlation compared to elementary collisions is observed at all Delta eta. As in p+p collisions, the near side is characterized by a peak of correlated partners at small angle relative to the trigger particle. However, in central Au+Au collisions an additional correlation extended in Delta eta and known as the "ridge" is found to reach at least |Delta eta| approximately = 4. The ridge yield is largely independent of Delta eta over the measured range, and it decreases towards more peripheral collisions. For the chosen (p(T)(trig) cut, the ridge yield is consistent with zero for events with less than roughly 100 participating nucleons.

System size, energy, pseudorapidity, and centrality dependence of elliptic flow.

This Letter presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider. The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system.

Using fluorescently labelled M13-tailed primers to isolate 45 novel microsatellite loci from the arboviral vector Culex tarsalis.

Culex tarsalis Coquillett (Diptera: Culicidae) is a highly efficient arbovirus vector. Spatial and temporal heterogeneity have been observed in Cx tarsalis for phenotypic traits including autogeny, virus susceptibility and host preference. Genetic differences between populations may in part explain these observations. Using the M13-tailed primer method, we identified 45 novel polymorphic microsatellite markers from microsatellite-enriched Cx tarsalis genomic libraries. The M13-tailed primer method was more efficient in identifying useful loci than traditional screening by acrylamide gel electrophoresis. These markers will be useful for investigating genetic questions in this important vector mosquito.

Evidence for a population expansion in the West Nile virus vector Culex tarsalis.

Population genetic structure of the West Nile Virus vector Culex tarsalis was investigated in 5 states in the western United States using 5 microsatellite loci and a fragment of the mitochondrial reduced form of nicotinamide adenine dinucleotide dehydrogenase 4 (ND4) gene. ND4 sequence analysis revealed a lack of isolation by distance, panmixia across all populations, an excess of rare haplotypes, and a star-like phylogeny. Microsatellites revealed moderate genetic differentiation and isolation by distance, with the largest genetic distance occurring between populations in southern California and New Mexico (F(ST) = 0.146). Clustering analysis and analysis of molecular variance on microsatellite data indicated the presence of 3 broad population clusters. Mismatch distributions and site-frequency spectra derived from mitochondrial ND4 sequences displayed pattern's characteristic of population expansion. Fu and Li's D* and F*, Fu's F(S), and Tajima's D statistics performed on ND4 sequences all revealed significant, negative deviations from mutation-drift equilibrium. Microsatellite-based multilocus heterozygosity tests showed evidence of range expansion in the majority of populations. Our results suggest that C. tarsalis underwent a range expansion across the western United States within the last 375,000-560,000 years, which may have been associated with Pleistocene glaciation events that occurred in the midwestern and western United States between 350,000 and 1 MYA.

Energy dependence of directed flow over a wide range of pseudorapidity in Au + Au collisions at the BNL Relativistic Heavy Ion Collider.

We report on measurements of directed flow as a function of pseudorapidity in Au + Au collisions at energies of square root of SNN = 19.6, 62.4, 130 and 200 GeV as measured by the PHOBOS detector at the BNL Relativistic Heavy Ion Collider. These results are particularly valuable because of the extensive, continuous pseudorapidity coverage of the PHOBOS detector. There is no significant indication of structure near midrapidity and the data surprisingly exhibit extended longitudinal scaling similar to that seen for elliptic flow and charged particle pseudorapidity density.

[Scope and limitations of diagnostics in breast disease--focussing on large core biopsy]. / Möglichkeiten und Grenzen der Mammadiagnostik unter besonderer Berücksichtigung der perkutanen Stanzbiopsie.

Percutaneous high speed large core biopsy (LCB) using a 14-gauge-needle, supported by sonographic procedures, is a safe and reliable method for the diagnosis of benign and malignant breast lesions in daily practice. All malignant diagnoses (B5)--comprising 44 % (267/604) of cases--were confirmed by subsequent surgical biopsy. This indicates a positive predictive value of 100 %. Evidence for uncertain dignity in LCB (categories B3 and B4) was found in 3 % of our cases (20/604), requiring open breast surgery for further clarification. This is strongly supported by the fact that 22 % of B3 and 82 % of B4 cases were identified as carcinomas in subsequent surgery. In 9 % of our cases (53/604), histology was only questionably representative (category B1) without cancer in the follow-up. In the B2-category--which comprised nearly 44 % of all cases (n = 263)--the positive predictive value ranged at 2 %. For clinical investigation, mammography, breast ultrasound and LCB the sensitivity were at 79 %, 92 %, 92 % and 98 %, respectively. The specificity of clinical findings, mammography, breast ultrasound and LCB ranged at 88 %, 67 %, 79 % and 99 %, respectively. The combination of the 3 methods: clinical findings, mammography and breast ultrasound (leading to a "total diagnostic score" provided a sensitivity and specificity of 97 % and 52 %. LCB revealed an excellent specificity of 99 %. Therefore, large core biopsy takes up a definite and reliable place in procedures of breast diagnostics, thereby preventing a high number of unnecessary open surgical interventions.

Energy dependence of elliptic flow over a large pseudorapidity range in Au+Au collisions at the BNL relativistic heavy ion collider.

This Letter describes the measurement of the energy dependence of elliptic flow for charged particles in Au+Au collisions using the PHOBOS detector at the Relativistic Heavy Ion Collider. Data taken at collision energies of square root of s(NN)=19.6, 62.4, 130, and 200 GeV are shown over a wide range in pseudorapidity. These results, when plotted as a function of eta(')=|eta|-y(beam), scale with approximate linearity throughout eta('), implying no sharp changes in the dynamics of particle production as a function of pseudorapidity or increasing beam energy.

Centrality dependence of charged hadron transverse momentum spectra in Au+Au collisions from sqrt[s(NN)]=62.4 to 200 GeV.

We have measured transverse momentum distributions of charged hadrons produced in Au+Au collisions at sqrt[s(NN)]=62.4 GeV. The spectra are presented for transverse momenta 0.25

pp32 reduction induces differentiation of TSU-Pr1 cells.

pp32 (ANP32A) is a nuclear phosphoprotein expressed as a nonmutated form in self-renewing cell populations and neoplastic cells. Mechanistically, pp32 may regulate pathways important in the process of differentiation as part of separate complexes inhibiting histone acetylation and regulating immediate-early and cytokine mRNA stability. Prostatic adenocarcinomas express pp32 in a differentiation related manner-well-differentiated tumors express lower levels of pp32 than poorly differentiated tumors. In benign prostate, pp32 is expressed in basal cells but not in terminally differentiated glandular cells. Based on these observations, we hypothesized that reduction of pp32 expression might be an important differentiation signal. We used anti-sense pp32 and RNAi transfection to study the effects of reduced pp32 expression in the TSU-Pr1 carcinoma cell line. pp32 reduction induced TSU-Pr1 cells to differentiate into neuronal-like cells with associated inhibition of growth. Reduction of pp32 and consequent differentiation were accompanied by a marked reduction in expression of SET, which complexes with pp32, by a marked change in acetylation status of histone H4, and by further differential expression of genes in differentiation pathways. Thus, reduction of pp32 in the undifferentiated TSU-Pr1 neoplastic cell line induces differentiation and thus may be an element of a differentiation control pathway in both normal and neoplastic cells.

Serious complications that require surgical interventions after endoluminal stent-graft placement for the treatment of infrarenal aortic aneurysms.

BACKGROUND: Endoluminal stent-graft placement for the treatment of infrarenal abdominal aortic aneurysms has gained widespread acceptance because it is associated with lower peri-interventional morbidity than conventional transabdominal surgery. In this study the long-term morbidity of the procedure was evaluated. METHODS AND RESULTS: Between September 1994 and December 1998, 150 patients (age, 69.6 +/- 8.49 years; 142 men, 8 women) with abdominal aortic aneurysms were treated with the placement of an intravascular nitinol stent-graft (Stentor [55] and Vanguard-System [95]); there were eight tubular grafts and 142 bifurcated grafts. Initial placement of the stent-graft was successful in 144 patients. Mean follow-up was 49 +/- 25 months. In 13.3% of stent-graft placements we encountered the following complications: 4 cases of migration or dislocation of the prosthesis (30.5 +/- 7.4 months after placement); 2 ruptures of the aorta (26.7 and 15.0 months after placement); 3 recurrent thromboses of the stent-graft (25.5 +/- 5.3 months after placement); 3 endoleaks (27.5 +/- 15.7 months after placement); and 5 infections of the prosthesis (26.6 +/- 16.5 months after placement). There was no correlation between the complications and the type of stent used. All of these patients were treated by surgical replacement of the prosthesis with a Dacron graft. CONCLUSIONS: (1) The results suggest that most complications are due to a continuation of the disease process leading to loosening of the prosthesis. (2) Explantation of the prosthesis and surgical repair is feasible but bears additional risks. (3) Because the onset of reperfusion of the excluded aneurysm cannot be predicted, all patients with infrarenal aortic stent-grafts require frequent computer tomographic follow-up. (4) Finally, the results call for further improvements in the design of the stent-graft.

Pharmacokinetics, metabolism, and excretion of linezolid following an oral dose of [(14)C]linezolid to healthy human subjects.

Linezolid (Zyvox), the first of a new class of antibiotics, the oxazolidinones, is approved for treatment of Gram-positive bacterial infections, including resistant strains. The disposition of linezolid in human volunteers was determined, after a 500-mg (100-microCi) oral dose of [(14)C]linezolid. Radioactive linezolid was administered as a single dose, or at steady-state on day 4 of a 10-day, 500-mg b.i.d. regimen of unlabeled linezolid (n = 4/sex/regimen). Mean recovery of radioactivity in excreta was 93.8 +/- 1.1% (range 91.2-95.2%, n = 15), of which 83.9 +/- 3.3% (range 76.7-88.4%) was in urine and 9.9 +/- 3.4% (range 5.3-16.9%) was in feces. There was no major difference in rate or route of excretion of radioactivity by dose regimen. Linezolid was excreted primarily intact, and as two inactive, morpholine ring-oxidized metabolites, PNU-142586 and PNU-142300. Other minor metabolites were characterized by high-performance liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry and (19)F NMR spectroscopy. After the single radioactive dose, linezolid was the major circulating drug-related material accounting for about 78% (male) and 93% (female) of the radioactivity area under the curve (AUC). PNU-142586 (T(max) of 3-5 h) accounted for about 26% (male) and 9% (female) of the radioactivity AUC. PNU-142300 (T(max) of 2-3 h) accounted for about 7% (male) and 4% (female) of the radioactivity AUC. Overall, mean linezolid and PNU-142586 exposures at steady-state were similar across sex. In conclusion, linezolid circulates in plasma mainly as parent drug. Linezolid and two major, inactive metabolites account for the major portion of linezolid disposition, with urinary excretion representing the major elimination route. Formation of PNU-142586 was the rate-limiting step in the clearance of linezolid.

Dapsone activation of CYP2C9-mediated metabolism: evidence for activation of multiple substrates and a two-site model.

Dapsone activates CYP2C9-mediated metabolism in various expression systems and is itself metabolized by CYP2C9 to its hydroxylamine metabolite. Studies were conducted with expressed CYP2C9 to characterize the kinetic effects of dapsone (0-100 microM) on (S)-flurbiprofen (2-300 microM), (S)-naproxen (10-1800 microM), and piroxicam (5-900 microM) metabolism in 6 x 6 matrix design experiments. The influence of (S)-flurbiprofen on dapsone hydroxylamine formation was also studied. Dapsone increased the Michaelis-Menten-derived V(max) of flurbiprofen 4'-hydroxylation from 12.6 to 20.6 pmol/min/pmol P450, and lowered its K(m) from 28.9 to 10.0 microM, suggesting that dapsone activates CYP2C9-mediated flurbiprofen metabolism without displacing flurbiprofen from the active site, supporting a two-site model describing activation. Similar results were observed with piroxicam 5'-hydroxylation, as V(max) was increased from 0.08 to 0.20 pmol/min/pmol P450 and K(m) was decreased from 183 to 50 microM in the presence of dapsone. In addition, the kinetic profile for naproxen was converted from biphasic to hyperbolic in the presence of dapsone, while exhibiting similar decreases in K(m) and increases in V(max). Kinetic parameters were also estimated using the two-site binding equation, with alpha values <1 and beta values >1, indicative of activation. Additionally, dapsone hydroxylamine formation was measured from incubations containing flurbiprofen, exhibiting a kinetic profile that was minimally affected by the presence of flurbiprofen. Overall, these results suggest that dapsone activates the metabolism of multiple substrates of CYP2C9 by binding within the active site and causing positive cooperativity, thus lending further support to a two-site binding model of P450-mediated metabolism.

Percutaneous endoprosthesis for treatment of aortic aneurysms.

The purpose of this study was to define the clinical utility of stent-grafts for endoluminal treatment of infrarenal abdominal aortic aneurysms (AAAs). In a prospective study involving three centers, bifurcated stent-grafts for endovascular repair of infrarenal AAAs were implanted in 295 patients. Patient selection was based on anatomic suitability. For analysis of the initial and follow-up results the patients were divided in three subgroups. Group 1 included patients treated between August 1994 and April 1996 with use of the original stent-graft device; group 2 comprised patients treated between May 1996 and December 1997 with the refined stent-graft device, and group 3 comprised patients treated with a newly designed bifurcated stent-graft device. In group 1 (n = 111) the primary technical success was 82%. The procedure had to be converted to surgery in four patients. Endoleaks immediately after the procedure were observed in 16 patients. The initial technical success in subgroup 2 (n = 159) was 96%. One patient required surgical repair, and five others had immediate perigraft flow due to reperfusion via lumbar arteries. For group 3 (n = 28) the primary technical success rate was 89%. Endoleaks due to back-bleeding via lumbar arteries were demonstrated in three patients. Minor and major complications related to the intervention, including two perioperative deaths, were observed in 24 patients (8%). Serious problems such as distal migration or disconnection of the stent-graft were detected during follow-up in five patients. Delayed aortic rupture occurred in three patients who survived after successful surgical repair. Based on the initial results and a limited follow-up of 35 months, we believe endoluminal repair of infrarenal AAA with use of bifurcated endografts may be a feasible alternative to conventional surgery, especially for patients at high surgical risk. However, at the present time there are major concerns with respect to the structural integrity of stent-graft material and the fate of the proximal aortic cuff in the long-term time frame.

The knee joint in early juvenile idiopathic arthritis. An ROC study for evaluating the diagnostic accuracy of contrast-enhanced MR imaging.

PURPOSE: Diagnosis of juvenile idiopathic arthritis (JIA) remains difficult due to unspecific clinical and laboratory findings, especially in early stages of the disease. The purpose of our study was to determine the sensitivity and specificity of MR imaging in diagnosing JIA of the knee joints. MATERIAL AND METHODS: Forty children (3-17 years old) clinically diagnosed with JIA (follow-up > 1 year) of a knee joint and a control group of 40 children with painful knee joints (MR diagnosis: bone bruise of the knee (n = 7), normal knee joint (n = 12), osteomyelitis (n = 6), septic arthritis (n = 2), bone tumor (n = 7) and miscellaneous bone lesions (n = 6)) were examined using a 1.5 T MR unit. T1-weighted spin-echo (SE), T2-weighted fast SE, contrast-enhanced T1-weighted SE and 2D gradient echo sequences were performed. The receiver operating characteristic (ROC) curves evaluation was conducted by 5 independent radiologists. RESULTS: The positive criteria for diagnosing JIA were joint effusions (n = 40), contrast-enhancing synovitis (n = 39), cartilage lesions (n = 15), subchondral erosions and bony destruction (n = 1). Sensitivity and specificity were 93.5% and 92.5%, respectively. Both cases of septic arthritis were misdiagnosed as JIA by all radiologists. CONCLUSION: Contrast-enhanced MR imaging seems to be a highly sensitive tool in establishing the diagnosis of JIA.

Interaction of delavirdine with human liver microsomal cytochrome P450: inhibition of CYP2C9, CYP2C19, and CYP2D6.

Delavirdine, a non-nucleoside inhibitor of HIV-1 reverse transcriptase, is metabolized primarily through desalkylation catalyzed by CYP3A4 and CYP2D6 and by pyridine hydroxylation catalyzed by CYP3A4. It is also an irreversible inhibitor of CYP3A4. The interaction of delavirdine with CYP2C9 was examined with pooled human liver microsomes using diclofenac 4'-hydroxylation as a reporter of CYP2C9 catalytic activity. As delavirdine concentration was increased from 0 to 100 microM, the K(M) for diclofenac metabolism rose from 4.5+/-0.5 to 21+/-6 microM, and V(max) declined from 4.2+/-0.1 to 0.54+/-0.08 nmol/min/mg of protein, characteristic of mixed-type inhibition. Nonlinear regression analysis revealed an apparent K(i) of 2.6+/-0.4 microM. There was no evidence for bioactivation as prerequisite to inhibition of CYP2C9. Desalkyl delavirdine, the major circulating metabolite of delavirdine, had no apparent effect on microsomal CYP2C9 activity at concentrations up to 20 microM. Several analogs of delavirdine showed similar inhibition of CYP2C9. Delavirdine significantly inhibited cDNA-expressed CYP2C19-catalyzed (S)-mephenytoin 4'-hydroxylation in a noncompetitive manner, with an apparent K(i) of 24+/-3 microM. Delavirdine at concentrations up to 100 microM did not inhibit the activity of CYP1A2 or -2E1. Delavirdine competitively inhibited recombinant CYP2D6 activity with a K(i) of 12.8+/-1.8 microM, similar to the observed K(M) for delavirdine desalkylation. These results, along with previously reported experiments, indicate that delavirdine can partially inhibit CYP2C9, -2C19, -2D6, and -3A4, although the degree of inhibition in vivo would be subject to a variety of additional factors.