Fluctuations, Saturation, and Diffractive Excitation in High Energy Collisions

Diffractive excitation is usually described by the Good--Walker formalism for low masses, and by the triple-Regge formalism for high masses. In the Good--Walker formalism the cross section is determined by the fluctuations in the interaction. In this paper we show that by taking the fluctuations in the BFKL ladder into account, it is possible to describe both low and high mass excitation by the Good--Walker mechanism. In high energy $pp$ collisions the fluctuations are strongly suppressed by saturation, which implies that pomeron exchange does not factorise between DIS and $pp$ collisions. The Dipole Cascade Model reproduces the expected triple-Regge form for the bare pomeron, and the triple-pomeron coupling is estimated.Comment: 20 pages, 12 figure

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Critical Appraisal of Four IL-6 Immunoassays

BACKGROUND: Interleukin-6 (IL-6) contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs), with expected rises in IL-6 concentrations, were used to test the face validity of the various assays. METHODS AND FINDINGS: IVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass) at time zero, a single infusion of insulin (0.025 U/kg body mass) at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD), an Invitrogen Luminex bead-based multiplex panel (LX), an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX), and R&D High Sensitivity ELISA (R&D). IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001) but only ULX correlated (r = 0.31, p = 0.0027) with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL) increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049), and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048). CONCLUSION: This study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1-2 hours) and a late insulin-dependent response (detectable after 2 hours)

The effects of spatial legacies following shifting management practices and fire on boreal forest age structure

Forest age structure and its spatial arrangement are important elements of sustainable forestry because of their effects on biodiversity and timber availability. Forest management objectives that include specific forest age structure may not be easily attained due to constraints imposed by the legacies of historical management and natural disturbance. We used a spatially explicit stochastic model to explore the synergetic effects of forest management and fire on boreal forest age structure. Specifically, we examined (1) the duration of spatial legacies of different management practices in the boreal forest, (2) how multiple shifts in management practices affect legacy duration and the spatial trajectories of forest age structure, and (3) how fire influences legacy duration and pattern development in combination with harvesting. Results based on 30 replicates of 500 years for each scenario indicate that (1) spatial legacies persist over 200 years and the rate at which legacies are overcome depends on whether new management targets are in synchrony with existing spatial pattern; (2) age specific goals were met faster after multiple management shifts due to the similar spatial scale of the preceding management types; (3) because large fires can erase the spatial pattern created by smaller disturbances, scenarios with fire had shorter lags than scenarios without fire. These results suggest that forest management goals can be accelerated by applying management at a similar spatial scale as existing spatial patterns. Also, management planning should include careful consideration of historical management as well as current and likely future disturbances

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0–32) years before and median 4 (0–35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0–1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1–33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS

Tumor-associated macrophages in clear cell renal cell carcinoma express both gastrin-releasing peptide and its receptor: a possible modulatory role of immune effectors cells

Renal cell carcinomas (RCC) frequently express the gastrin-releasing peptide receptor (GRP-R). Gastrin-releasing peptide (GRP) stimulates tumor cell proliferation and neoangiogenesis. Tumor-associated macrophages (TAM) comprise an important cellular component of these tumors. We analyzed the GRP/GRP-R network in clear cell RCC (ccRCC) and non-clear cell RCC (non-ccRCC) with special regard to its expression by macrophages, tumor cells and microvessels. Gastrin-releasing peptide and GRP-R expression in 17 ccRCC and 9 non-ccRCC were analyzed by RT-PCR, immunohistochemistry and double immunofluorescence staining. Tumor-associated macrophages expressed GRP and GRP receptor in ccRCC. Tumor cells and microvessels showed low to intermediate GRP-R expression in nearly all cases. In 12 ccRCC tumor epithelia also expressed low levels of GRP. Microvascular GRP expression was found in nine cases of ccRCC. For non-RCC, the expression of GRP and GRP receptor expression pattern was similar. Tumor-associated macrophages are the main source of GRP in RCC. GRP receptor on TAM, tumor epithelia and microvessels might be a molecular base of a GRP/GRP receptor network, potentially acting as a paracrine/autocrine modulator of TAM recruitment, tumor growth and neoangiogenesis

Standard versus prosocial online support groups for distressed breast cancer survivors: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The Internet can increase access to psychosocial care for breast cancer survivors through online support groups. This study will test a novel prosocial online group that emphasizes both opportunities for getting and giving help. Based on the helper therapy principle, it is hypothesized that the addition of structured helping opportunities and coaching on how to help others online will increase the psychological benefits of a standard online group.</p> <p>Methods/Design</p> <p>A two-armed randomized controlled trial with pretest and posttest. Non-metastatic breast cancer survivors with elevated psychological distress will be randomized to either a standard facilitated online group or to a prosocial facilitated online group, which combines online exchanges of support with structured helping opportunities (blogging, breast cancer outreach) and coaching on how best to give support to others. Validated and reliable measures will be administered to women approximately one month before and after the interventions. Self-esteem, positive affect, and sense of belonging will be tested as potential mediators of the primary outcomes of depressive/anxious symptoms and sense of purpose in life.</p> <p>Discussion</p> <p>This study will test an innovative approach to maximizing the psychological benefits of cancer online support groups. The theory-based prosocial online support group intervention model is sustainable, because it can be implemented by private non-profit or other organizations, such as cancer centers, which mostly offer face-to-face support groups with limited patient reach.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01396174">NCT01396174</a></p

RNAi-Mediated Knock-Down of Arylamine N-acetyltransferase-1 Expression Induces E-cadherin Up-Regulation and Cell-Cell Contact Growth Inhibition

Arylamine N-acetyltransferase-1 (NAT1) is an enzyme that catalyzes the biotransformation of arylamine and hydrazine substrates. It also has a role in the catabolism of the folate metabolite p-aminobenzoyl glutamate. Recent bioinformatics studies have correlated NAT1 expression with various cancer subtypes. However, a direct role for NAT1 in cell biology has not been established. In this study, we have knocked down NAT1 in the colon adenocarcinoma cell-line HT-29 and found a marked change in cell morphology that was accompanied by an increase in cell-cell contact growth inhibition and a loss of cell viability at confluence. NAT1 knock-down also led to attenuation in anchorage independent growth in soft agar. Loss of NAT1 led to the up-regulation of E-cadherin mRNA and protein levels. This change in E-cadherin was not attributed to RNAi off-target effects and was also observed in the prostate cancer cell-line 22Rv1. In vivo, NAT1 knock-down cells grew with a longer doubling time compared to cells stably transfected with a scrambled RNAi or to parental HT-29 cells. This study has shown that NAT1 affects cell growth and morphology. In addition, it suggests that NAT1 may be a novel drug target for cancer therapeutics

Global, local and focused geographic clustering for case-control data with residential histories

BACKGROUND: This paper introduces a new approach for evaluating clustering in case-control data that accounts for residential histories. Although many statistics have been proposed for assessing local, focused and global clustering in health outcomes, few, if any, exist for evaluating clusters when individuals are mobile. METHODS: Local, global and focused tests for residential histories are developed based on sets of matrices of nearest neighbor relationships that reflect the changing topology of cases and controls. Exposure traces are defined that account for the latency between exposure and disease manifestation, and that use exposure windows whose duration may vary. Several of the methods so derived are applied to evaluate clustering of residential histories in a case-control study of bladder cancer in south eastern Michigan. These data are still being collected and the analysis is conducted for demonstration purposes only. RESULTS: Statistically significant clustering of residential histories of cases was found but is likely due to delayed reporting of cases by one of the hospitals participating in the study. CONCLUSION: Data with residential histories are preferable when causative exposures and disease latencies occur on a long enough time span that human mobility matters. To analyze such data, methods are needed that take residential histories into account