Covering Points by Disjoint Boxes with Outliers

For a set of n points in the plane, we consider the axis--aligned (p,k)-Box Covering problem: Find p axis-aligned, pairwise-disjoint boxes that together contain n-k points. In this paper, we consider the boxes to be either squares or rectangles, and we want to minimize the area of the largest box. For general p we show that the problem is NP-hard for both squares and rectangles. For a small, fixed number p, we give algorithms that find the solution in the following running times: For squares we have O(n+k log k) time for p=1, and O(n log n+k^p log^p k time for p = 2,3. For rectangles we get O(n + k^3) for p = 1 and O(n log n+k^{2+p} log^{p-1} k) time for p = 2,3. In all cases, our algorithms use O(n) space.Comment: updated version: - changed problem from 'cover exactly n-k points' to 'cover at least n-k points' to avoid having non-feasible solutions. Results are unchanged. - added Proof to Lemma 11, clarified some sections - corrected typos and small errors - updated affiliations of two author

An unexpected symbiosis of animal welfare and clinical relevance in a refined nonhuman primate model of human autoimmune disease

Aging Western populations are confronted with an increasing prevalence of chronic inflammatory and degenerative diseases for which adequate treatments are lacking. One of the major hurdles in therapy development is the poor translation of disease concepts, often developed in rodent disease models, into effective treatments for the patient. Reasons for the high failure rate of promising drug candidates are unforeseen toxicity and lack of efficacy. Essential elements of human disease are apparently lacking in the current preclinically used animal models. Results obtained in a generic nonhuman primate model of human autoimmunity, the marmoset experimental autoimmune encephalomyelitis (EAE) model, are discussed to emphasize the claim that primates are essential complementary models that can help to bridge the wide translational gap between mouse and man.</p

Incidence and diagnostic yield of repeat urine culture in hospitalized patients: An opportunity for diagnostic stewardship

There is limited knowledge on the incidence, diagnostic yield, and cost associated with inappropriate repeat urine cultures. The factors that affect repeat urine culturing practices are not well understood. We conducted a retrospective study of adult inpatients who had ≥1 urine culture performed during their hospitalization between January 2015 and February 2018. We analyzed the proportion of inappropriate repeat urine cultures performed \u3c48 h after the index culture. We defined an inappropriate repeat urine culture to be a repeat urine culture performed following a negative index culture or a repeat urine specimen obtained from the same urinary catheter. Overall, 28,141 urine cultures were performed on 21,306 patients. There were 2,060 (7.3%) urine cultures repeated in \u3c48 h. Of these, 1,120 (54.4%) urine cultures were inappropriate. Predictors for inappropriate repeat urine cultures included collection of the initial urine sample for culture in the emergency department (adjusted odds ratio [aOR], 5.65; 95% confidence interval [CI], 4.70 to 6.78), male gender (aOR, 1.61; 95% CI, 1.42 to 1.84), congestive heart failure (aOR, 1.20; 95% CI, 1.03 to 1.38), and a longer hospital stay (aOR, 1.01 per day; 95% CI, 1.00 to 1.01). A patient with an index urine culture obtained from an indwelling catheter (aOR, 0.65; 95% CI, 0.53 to 0.80) was less likely to have an inappropriate repeat culture. Among 1,120 negative index urine cultures, only 4.7% of repeat cultures were positive for bacteriuria. The estimated laboratory charges for inappropriate repeat urine cultures were $16,800 over the study period. Among inpatients, over half of all urine cultures repeated in \u3c48 h were inappropriate. This offers an opportunity for diagnostic stewardship and optimization of antimicrobial use

The Nature of the Nuclear H2O Masers of NGC 1068: Reverberation and Evidence for a Rotating Disk Geometry

We report new (1995) Very Large Array observations and (1984 - 1999) Effelsberg 100m monitoring observations of the 22 GHz H2O maser spectrum of the Seyfert 2 galaxy NGC 1068. The sensitive VLA observations provide a registration of the 22 GHz continuum emission and the location of the maser spots with an accuracy of ~ 5 mas. Within the monitoring data, we find evidence that the nuclear masers vary coherently on time-scales of months to years, much more rapidly than the dynamical time-scale. We argue that the nuclear masers are responding in reverberation to a central power source, presumably the central engine. Between October and November 1997, we detected a simultaneous flare of the blue-shifted and red-shifted satellite maser lines. Reverberation in a rotating disk naturally explains the simultaneous flaring. There is also evidence that near-infrared emission from dust grains associated with the maser disk also responds to the central engine. We present a model in which an X-ray flare results in both the loss of maser signal in 1990 and the peak of the near-infrared light curve in 1994. In support of a rotating disk geometry for the nuclear masers, we find no evidence for centripetal accelerations of the redshifted nuclear masers; the limits are +/- 0.006 km/s/year, implying that the masers are located within 2 degrees of the kinematic line-of-nodes. We also searched for high velocity maser emission like that observed in NGC 4258. In both VLA and Effelsberg spectra, we detect no high velocity lines between +/- 350 km/s to +/- 850 km/s relative to systemic, arguing that masers only lie outside a radius of ~ 0.6 pc (1.9 light years) from the central engine (assuming a distance of 14.4 Mpc).Comment: 62 pages, 19 figure

Severe oxidative stress in an acute inflammatory demyelinating model in the rhesus monkey

Oxidative stress is increasingly implicated as a co-factor of tissue injury in inflammatory/demyelinating disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While rodent experimental autoimmune encephalomyelitis (EAE) models diverge from human demyelinating disorders with respect to limited oxidative injury, we observed that in a non-human primate (NHP) model for MS, namely EAE in the common marmoset, key pathological features of the disease were recapitulated, including oxidative tissue injury. Here, we investigated the presence of oxidative injury in another NHP EAE model, i.e. in rhesus macaques, which yields an acute demyelinating disease, which may more closely resemble acute disseminated encephalomyelitis (ADEM) than MS. Rhesus monkey EAE diverges from marmoset EAE by abundant neutrophil recruitment into the CNS and destructive injury to white matter. This difference prompted us to investigate to which extent the oxidative pathway features elicited in MS and marmoset EAE are reflected in the acute rhesus monkey EAE model. The rhesus EAE brain was characterized by widespread demyelination and active lesions containing numerous phagocytic cells and to a lesser extent T cells. We observed induction of the oxidative stress pathway, including injury, with a predilection of p22phox expression in neutrophils and macrophages/microglia. In addition, changes in iron were observed. These results indicate that pathogenic mechanisms in the rhesus EAE model may differ from the marmoset EAE and MS brain due to the neutrophil involvement, but may in the end lead to similar induction of oxidative stress and injury.</p

Effects of Early IL-17A Neutralization on Disease Induction in a Primate Model of Experimental Autoimmune Encephalomyelitis

We report on the effect of antibody-mediated neutralization of interleukin (IL)-17A in a non-human primate experimental autoimmune encephalomyelitis (EAE) model induced with recombinant human myelin oligodendrocyte glycoprotein (rhMOG). We tested a human-anti-human IL-17A-antibody in two doses (3 and 30 mg/kg) against placebo (PBS). The treatment was started 1 day before EAE induction and continued throughout the experiment. Although all monkeys developed clinically evident EAE, the onset of neurological signs was delayed in some monkeys from both treatment groups. Total CNS lesion volumes, demyelination, or inflammation did not differ between the different groups. Immune profiling revealed an altered distribution of IL-17A producing cells in the lymphoid organs of antibody-treated monkeys. Comparable numbers of IL-17A producing cells were observed in the brain. RhMOG-induced T cell proliferation in the lymph nodes was slightly reduced after anti-IL-17A antibody treatment. To summarize, we found that anti-IL-17A antibody as a single treatment from disease induction effects a trend towards delayed neurological disease progression in the marmoset EAE model, although the effect did not reach statistical significance. This suggests a role of IL-17A in late stage disease in the marmoset EAE model, but IL-17A may not be the dominant pathogenic cytokine

Crystal Structure of Monoclonal 6B5 Fab Complexed with Phencyclidine

The crystal structure of monoclonal antibody (mAb) 6B5 Fab fragment complexed with 1-(1-phenylcyclohexyl)piperidine (PCP or phencyclidine) was determined at 2.2-A resolution. 6B5 was originally produced from a mouse immunized with a phencyclidine analogue hapten 5-[N-(1'phenylcyclohexyl)amino]pentanoic acid conjugated to bovine serum albumin. This mAb was selected for further study because of its high affinity (Kd = 2 x 10(-9) M/liter) for PCP and usefulness in reversing PCP-induced central nervous system toxicity in laboratory animals. The dominant feature of the 6B5 Fab.PCP complex is the deep binding site and hydrophobic nature of the interaction. The ligand binding pocket of 6B5 Fab has numerous aromatic side chains, as compared with other known Fab structures. The most notable feature of the binding site is a Trp at position 97H (H-chain), and the side chain of this residue appears to act as a hydrophobic umbrella on the ligand in the antigen binding pocket. There are only two other known Fabs found with a Trp at the 97H position in complementarity determining region (CDR) H3, but they do not play a major role in the interaction with their respective antigens; in both Fab TE33 and R6.5 the Trp 97H side chain is positioned away from the bound antigen. Comparison of the CDR residues of 6B5 with other Fab structures with similar CDR sizes and amino acid compositions reveals a number of important patterns of residue substitutions that appear to be critical for specific PCP ligand interactions

XMM-Newton survey of the Local Group galaxy M 33

In an XMM-Newton raster observation of the bright Local Group spiral galaxy M 33 we study the population of X-ray sources (X-ray binaries, supernova remnants) down to a 0.2--4.5 keV luminosity of 10^35 erg/s -- more than a factor of 10 deeper than earlier ROSAT observations. EPIC hardness ratios and optical and radio information are used to distinguish between different source classes. The survey detects 408 sources in an area of 0.80 square degree. We correlate these newly detected sources with earlier M 33 X-ray catalogues and information from optical, infra-red and radio wavelengths. As M 33 sources we detect 21 supernova remnants (SNR) and 23 SNR candidates, 5 super-soft sources, and 2 X-ray binaries (XRBs). There are 267 sources classified as hard, which may either be XRBs or Crab-like SNRs in M 33 or background AGN. The 44 confirmed and candidate SNRs more than double the number of X-ray detected SNRs in M 33. 16 of these are proposed as SNR candidates from the X-ray data for the first time. On the other hand, there are several sources not connected to M 33: five foreground stars, 30 foreground star candidates, 12 active galactic nucleus candidates, one background galaxy and one background galaxy candidate. Extrapolating from deep field observations we would expect 175 to 210 background sources in this field. This indicates that about half of the sources detected are sources within M 33.Comment: 14 pages, 6 figures, accepted for publication in A&A, the images of Figs. 1,2,3,4,6 are available in jpg format, a full version of the paper is available at ftp://ftp.xray.mpe.mpg.de/people/fwh/docs/M33_AA0068.p