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Lattice QCD (LQCD) has proven to be an important tool in understanding the tension between the experimental value for the anomalous magnetic moment of the muon (g − 2)μ and its prediction from the standard model. The lattice provides a non-perturbative method for evaluating the hadronic contributions to (g − 2)μ, which contributes the largest amount to the uncertainty of the theoretical prediction. Among these the hadronic vacuum polarization aμHVP is the dominant contribution. In order to match the uncertainty of the experiment, lattice QCD needs to reach sub-percent precision. This requires the calculation of QED corrections to aμHVP, which are represented by additional Feynman diagrams. We present a lattice calculation of the UV-finite (2+2) diagram at the SU(3) flavor symmetric point and compare this to the pseudoscalar meson exchange model with a vector-meson dominance parametrization of the transition form factor.

We present results for the electromagnetic form factors of the proton and neutron computed on the (2 + 1)-flavor Coordinated Lattice Simulations (CLS) ensembles including both quark-connected and -disconnected contributions. The Q2-, pion-mass, lattice-spacing, and finite-volume dependence of our form factor data is fitted simultaneously to the expressions resulting from covariant chiral perturbation theory including vector mesons amended by models for lattice artefacts. From these fits, we determine the electric and magnetic radii and the magnetic moments of the proton and neutron, as well as the Zemach radius of the proton. To assess the influence of systematic effects, we average over various cuts in the pion mass and the momentum transfer, as well as over different models for the lattice-spacing and finite-volume dependence, using weights derived from the Akaike Information Criterion (AIC).

Immunotherapy has become a cornerstone of the modern cancer treatment. It might be crucial to predict its expression non-invasively by imaging. The present study used diffusion-weighted imaging (DWI) quantified by whole lesion apparent diffusion coefficient (ADC) values to elucidate possible associations with programmed cell death ligand 1(PD-L1) expression in head and neck squamous cell cancer (HNSCC).

Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a solid tumor of extramedullary localization composed of malignant primitive myeloid cells. The purpose of the study was to identify clinical and imaging features in a large patient sample.

This study examined children's understanding of the danger and potential harm they face while traveling to and from school in two urban neighborhoods with high crime and violence rates. A qualitative methodology was used to explore how students negotiate danger or potential harm within the context of their routes to and from school. Structured interviews with three hundred seventy-seven second, fourth, sixth, and eighth graders (and 106 of their parents) were analyzed utilizing an inductive coding process (emergent themes). When students were asked to discuss the safety of their school routes, emergent themes included student's fear/awareness of death, fear of violence/victimization, and fear of gangs. Students also mentioned getting driven to school and better monitoring as ways that their school routes could be made safer. Parents discussed similar fears and concerns as their children. Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

The persistent discrepancy of about 3.5 standard deviations between the experimental measurement and the Standard Model prediction for the muon anomalous magnetic moment, aµ, is one of the most promising hints for the possible existence of new physics. Here we report on our lattice QCD calculation of the hadronic vacuum polarisation contribution aμhvp$ a_\mu ^{{\rm{hvp}}} $, based on gauge ensembles with Nf = 2 + 1 flavours of O(a) improved Wilson quarks. We address the conceptual and numerical challenges that one encounters along the way to a sub-percent determination of the hadronic vacuum polarisation contribution. The current status of lattice calculations of aμhvp$ a_\mu ^{{\rm{hvp}}} $ is presented by performing a detailed comparison with the results from other groups.

This paper presents the concept and design of a digital system to record seismological signals. The hardware and software designed has been interfaced to the PC 104 BUS architecture in order to achieve a modular system to acquire, process, record and transmit seismic data by telemetry. The modularity of this system offers independence technology from the manufacturers of this kind of equipments both in hardware and software, also because the system was developed under the Linux operating system GNU, which allows easy update of hardware; the software is an open platform developed in C, which allows the user to configure the system to operate online and updating according to needs.In brief, we propose in this paper a system design option for seismological instrumentation, which presents significant advantages also for other regions and countries with high seismicity and needs of earthquake monitoring, but have serious limitations in acquiring and maintaining commercial systems imported from developed countries.

We report on an analysis of the average quark momentum fraction of the nucleon and related quantities using Nf = 2 + 1 Wilson fermions. Computations are performed on four CLS ensembles covering three values of the lattice spacing at pion masses down to Mπ ≈ 200 MeV. Several source-sink separations (~ 1:0 fm to ~ 1:4 fm) are used to assess the excited-state contamination. To gain further insight, the generalized pencil-of-functions approach has been implemented to reduce the excited-state contamination in the relevant two-and three-point functions. Preliminary results are shown for the isovector nucleon charges from vector, axial vector and tensor derivative (twist-2) operators.

We present a new technique for extracting total transition rates into final states with any number of hadrons from lattice QCD. The method involves constructing a finite-volume Euclidean four-point function whose corresponding infinite-volume spectral function gives access to the decay and transition rates into all allowed final states. The inverse problem of calculating the spectral function is solved via the Backus-Gilbert method, which automatically includes a smoothing procedure. This smoothing is in fact required so that an infinite-volume limit of the spectral function exists. Using a numerical toy example we find that reasonable precision can be achieved with realistic lattice data. In addition, we discuss possible extensions of our approach and, as an example application, prospects for applying the formalism to study the onset of deep-inelastic scattering. More details are given in the published version of this work, Ref. [1].

We briefly review several activities at Mainz related to hadronic light-by-light scattering (HLbL) using lattice QCD. First we present a position-space approach to the HLbL contribution in the muon g̅2, where we focus on exploratory studies of the pion-pole contribution in a simple model and the lepton loop in QED in the continuum and in infinite volume. The second part describes a lattice calculation of the double-virtual pion transition form factor Fπ0γ*γ* (q21; q21) in the spacelike region with photon virtualities up to 1.5 GeV2 which paves the way for a lattice calculation of the pion-pole contribution to HLbL. The third topic involves HLbL forward scattering amplitudes calculated in lattice QCD which can be described, using dispersion relations (HLbL sum rules), by γ*γ* → hadrons fusion cross sections and then compared with phenomenological models.

The well-known discrepancy in the muon g − 2 between experiment and theory demands further theory investigations in view of the upcoming new experiments. One of the leading uncertainties lies in the hadronic light-by-light scattering contribution (HLbL), that we address with our position-space approach. We focus on exploratory studies of the pion-pole contribution in a simple model and the fermion loop without gluon exchanges in the continuum and in infinite volume. These studies provide us with useful information for our planned computation of HLbL in the muon g − 2 using full QCD.

We present an update on our determination of the electromagnetic form factors and axial charge of the nucleon from the Nf = 2 + 1 CLS ensembles with increased statistics and an additional finer lattice spacing. We also investigate the impact of O(a)-improvement of the currents.

We extend our previous studies [PhysRevD.90.054509, PhysRevD.92.094510] of the pion quasiparticle in the low-temperature phase of two-flavor QCD with support from chiral effective theory. This includes the analysis performed on a finite temperature ensemble of size 20 × 643 at T ≈ 151MeV and a lighter zero-temperature pion mass mπ ≈ 185 MeV. Furthermore, we investigate the Gell-Mann–Oakes-Renner relation at finite temperature and the Dey-Eletsky-Ioffe mixing theorem at finite quark mass.

We estimate the production rate of photons by the quark-gluon plasma in lattice QCD. We propose a new correlation function which provides better control over the systematic uncertainty in estimating the photon production rate at photon momenta in the range πT/2 to 2πT. The relevant Euclidean vector current correlation functions are computed with Nf = 2 Wilson clover fermions in the chirally-symmetric phase. In order to estimate the photon rate, an ill-posed problem for the vector-channel spectral function must be regularized. We use both a direct model for the spectral function and a modelindependent estimate from the Backus-Gilbert method to give an estimate for the photon rate.

We present our preliminary results on the calculation of hadronic light-by-light forward scattering amplitudes using vector four-point correlation functions computed on the lattice. Using a dispersive approach, forward scattering amplitudes can be described by γ*γ* → hadrons fusion cross sections and then compared with phenomenology. We show that only a few states are needed to reproduce our data. In particular, the sum rules considered in this study imply relations between meson–γγ couplings and provide valuable information about individual form factors which are often used to estimate the meson-pole contributions to the hadronic light-by-light contribution to the (g – 2) of the muon.

Abstract Background Recently we reported the validation of the “Allergy-Control-SCORE© (ACS)” which assesses symptom severity as well as medication use on three dimensions lung, nose and eyes. The aim of this study was to test the validity of the score for eyes and nose. Methods One-hundred-twenty-one consenting subjects (age 19-65y), including 81 patients with allergic rhino-conjunctivitis (RC) and 40 healthy controls, participated in the study. Patients rated daily nasal and eye symptoms using a 4-point scale (none, mild, moderate, and severe) and their use of anti-symptomatic medication. Validation criteria were pollen counts in the course of the study period. Discrimination capacity was analyzed by comparing the rhino-conjunctivitis Allergy-Control-SCORE© (RC-ACS©) values of allergic patients and healthy controls. Convergent reliability was assessed by correlating RC-ACS© values with the global severity of allergy, the quality of life, and the allergy-related medical consultations. Retest reliability was assessed by the correlation of the repeated measured RC-ACS© scores during each of two consecutive weeks. Results Convergent reliability analysis indicated a significant correlation between RC-Allergy-Control-SCORE© and global severity of allergy (r = 0.691; p r = 0.757; p r = 0.329; p = 0.0019). RC-Allergy-Control-SCORE© showed a good retest reliability (r = 0.813; p Conclusions The RC-ACS© can be considered as valid and reliable to assess the severity of rhino-conjunctivitis severity in clinical trials and observational studies.

Abstract Background There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks’ daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters. Methods Healthy adults aged 19–48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised). Results S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p 2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p Conclusions Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels. Trial Registration ClinicalTrials.gov: NCT01482689

Abstract Background The population in Norway has become multi-ethnic due to migration from Asia and Africa over the recent decades. The aim of the present study was to explore differences in the self-reported prevalence of cardiovascular disease (CVD) and associated risk factors by diabetes status in five ethnic minority groups compared to ethnic Norwegians. Methods Pooled data from three population-based cross-sectional studies conducted in Oslo between 2000 and 2002 was used. Of 54,473 invited individuals 24,749 (45.4%) participated. The participants self-reported health status, underwent a clinical examination and blood samples were drawn. A total of 17,854 individuals aged 30 to 61 years born in Norway, Sri-Lanka, Pakistan, Iran, Vietnam or Turkey were included in the study. Chi-square tests, one-way ANOVAs, ANCOVAs, multiple and logistic regression were used. Results Age- and gender-standardized prevalence of self-reported CVD varied between 5.8% and 8.2% for the ethnic minority groups, compared to 2.9% among ethnic Norwegians (p < 0.001). Prevalence of self-reported diabetes varied from 3.0% to 15.0% for the ethnic minority groups versus 1.8% for ethnic Norwegians (p < 0.001). Among individuals without diabetes, the CVD prevalence was 6.0% versus 2.6% for ethnic minorities and Norwegians, respectively (p < 0.001). Corresponding CVD prevalence rates among individuals with diabetes were 15.3% vs. 12.6% (p = 0.364). For individuals without diabetes, the odds ratio (OR) for CVD in the ethnic minority groups remained significantly higher (range 1.5-2.6) than ethnic Norwegians (p < 0.05), after adjustment for age, gender, education, employment, and body height, except for Turkish individuals. Regardless of diabetes status, obesity and physical inactivity were prevalent in the majority of ethnic minority groups, whereas systolic- and diastolic- blood pressures were higher in Norwegians. In nearly all ethnic groups, individuals with diabetes had higher triglycerides, waist-to-hip ratio (WHR), and body mass index compared to individuals without diabetes. Age, diabetes, hypertension, hypercholesterolemia, and WHR were significant predictors of CVD in both ethnic Norwegians and ethnic minorities, but significant ethnic differences were found for age, diabetes, and hypercholesterolemia. Conclusions Ethnic differences in the prevalence of CVD were prominent for individuals without diabetes. Primary CVD prevention including identification of undiagnosed diabetes should be prioritized for ethnic minorities without known diabetes.

Abstract Background South Asians living in western countries are known to have unfavourable cardiovascular risk profiles. Studies indicate migrants are worse off when compared to those living in country of origin. The purpose of this study was to compare selected cardiovascular risk factors between migrant Sri Lankans living in Oslo, Norway and Urban dwellers from Kandy, Sri Lanka. Methods Data on non fasting serum lipids, blood pressure, anthropometrics and socio demographics of Sri Lankan Tamils from two almost similar population based cross sectional studies in Oslo, Norway between 2000 and 2002 (1145 participants) and Kandy, Sri Lanka in 2005 (233 participants) were compared. Combined data were analyzed using linear regression analyses. Results Men and women in Oslo had higher HDL cholesterol. Men and women from Kandy had higher Total/HDL cholesterol ratios. Mean waist circumference and body mass index was higher in Oslo. Smoking among men was low (19.2% Oslo, 13.1% Kandy, P = 0.16). None of the women smoked. Mean systolic and diastolic blood pressure was significantly higher in Kandy than in Oslo. Conclusions Our comparison showed unexpected differences in risk factors between Sri Lankan migrants living in Oslo and those living in Kandy Sri Lanka. Sri Lankans in Oslo had favorable lipid profiles and blood pressure levels despite being more obese.

Abstract Background Based on previously reported differences in fracture incidence in the socioeconomic less affluent Oslo East compared to the more privileged West, our aim was to study bone mineral density (BMD) in the same socioeconomic areas in Oslo. We also wanted to study whether possible associations were explained by socio-demographic factors, level of education or lifestyle factors. Methods Distal forearm BMD was measured in random samples of the participants in The Oslo Health Study by single energy x-ray absorptiometry (SXA). 578 men and 702 women born in Norway in the age-groups 40/45, 60 and 75 years were included in the analyses. Socioeconomic regions, based on a social index dividing Oslo in two regions – East and West, were used. Results Age-adjusted mean BMD in women living in the less affluent Eastern region was 0.405 g/cm2 and significantly lower than in West where BMD was 0.419 g/cm2. Similarly, the odds ratio of low BMD (Z-score ≤ -1) was 1.87 (95% CI: 1.22–2.87) in women in Oslo East compared to West. The same tendency, although not statistically significant, was also present in men. Multivariate analysis adjusted for education, marital status, body mass index, physical inactivity, use of alcohol and smoking, and in women also use of post-menopausal hormone therapy and early onset of menopause, did hardly change the association. Additional adjustments for employment status, disability pension and physical activity at work for those below the age of retirement, gave similar results. Conclusion We found differences in BMD in women between different socioeconomic regions in Oslo that correspond to previously found differences in fracture rates. The association in men was not statistically significant. The differences were not explained by socio-demographic factors, level of education or lifestyle factors.

Abstract Background Persons of Pakistani origin living in Oslo have a much higher prevalence of vitamin D deficiency and secondary hyperparathyroidism but similar bone mineral density compared with ethnic Norwegians. Our objective was to investigate whether Pakistani immigrants living in Oslo have an altered vitamin D metabolism by means of compensatory higher serum levels of 1,25-dihydroxyvitamin D (s-1,25(OH)2D) compared with ethnic Norwegians; and whether serum levels of ionized calcium (s-Ca2+) differ between Pakistanis and Norwegians. Methods In a cross-sectional, population-based study venous serum samples were drawn from 94 Pakistani men and 67 Pakistani women aged 30–60 years, and 290 Norwegian men and 270 Norwegian women aged 45–60 years; in total 721 subjects. Results Pakistanis had lower s-1,25(OH)2D compared with Norwegians (p < 0.001). Age- and gender adjusted mean (95% CI) levels were 93 (86, 99) pmol/l in Pakistanis and 123 (120, 126) pmol/l in Norwegians, p < 0.001. The difference persisted after controlling for body mass index. There was a positive relation between serum 25-hydroxyvitamin D (s-25(OH)D) and s-1,25(OH)2D in both groups. S-Ca2+ was higher in Pakistanis; age-adjusted mean (95% CI) levels were 1.28 (1.27, 1.28) mmol/l in Pakistanis and 1.26 (1.26, 1.26) mmol/l in Norwegians, p < 0.001. In both groups, s-Ca2+ was inversely correlated to serum intact parathyroid hormone levels (s-iPTH). For any s-iPTH, s-Ca2+ was higher in Pakistanis, also when controlling for age. Conclusion Community-dwelling Pakistanis in Oslo with low vitamin D status and secondary hyperparathyroidism have lower s-1,25(OH)2D compared with ethnic Norwegians. However, the Pakistanis have higher s-Ca2+. The cause of the higher s-Ca2+ in Pakistanis in spite of their higher iPTH remains unclear.

Background: The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear.Methods: FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays.Results: High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p < 0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p < 0.001 and 0.09 resp.), but not in bladder or prostate cancer.Conclusion: The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors. [ABSTRACT FROM AUTHOR]

Background: To validate an artificial neural network (ANN) based on the combination of PSA velocity (PSAV) with a %free PSA-based ANN to enhance the discrimination between prostate cancer (PCa) and benign prostate hyperplasia (BPH).Methods: The study comprised 199 patients with PCa (n = 49) or BPH (n = 150) with at least three PSA estimations and a minimum of three months intervals between the measurements. Patients were classified into three categories according to PSAV and ANN velocity (ANNV) calculated with the %free based ANN "ProstataClass". Group 1 includes the increasing PSA and ANN values, Group 2 the stable values, and Group 3 the decreasing values.Results: 71% of PCa patients typically have an increasing PSAV. In comparison, the ANNV only shows this in 45% of all PCa patients. However, BPH patients benefit from ANNV since the stable values are significantly more (83% vs. 65%) and increasing values are less frequently (11% vs. 21%) if the ANNV is used instead of the PSAV.Conclusion: PSAV has only limited usefulness for the detection of PCa with only 71% increasing PSA values, while 29% of all PCa do not have the typical PSAV. The ANNV cannot improve the PCa detection rate but may save 11-17% of unnecessary prostate biopsies in known BPH patients. [ABSTRACT FROM AUTHOR]

Background: Research-focused faculty face barriers to research engagement and success. Definitions of research success vary among organizations, research teams, and individuals. An institution must identify barriers before implementing mitigation strategies., Purpose: To define research success, identify current barriers, and strategies to mitigate those barriers to increase research-focused faculty's research success., Methods: A qualitative research design incorporating focus groups and aspects of a modified Delphi approach was implemented at a research retreat with 22 attendees. Data were analyzed by content analysis., Findings: Measures of research success included dissemination, planning/organization, time, wellness, collaboration, mentoring, funding, impact and translation, and recognition. Top barriers were competing demands, time, team disputes, interpersonal relations, workload, resources, expectation differences, and funding success. Attendees identified these barriers as the focus for mitigation strategies., Discussion: Opportunities for collegial discussion, peer feedback, and dedicated meetings to discuss research ideas can help research-focused faculty increase their research success and productivity., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To investigate the prevalence of workplace violence (WPV) in home health care and long-term care facilities (LTCFs) and explore the relationship between WPV and worker well-being., Method: A cross-sectional survey was conducted with health care workers in an agency that provided care in homes or LTCFs. Six measures of worker well-being were collected: satisfaction with work and life, work-related rumination, work/family conflict, burnout, and turnover intention. Surveys also assessed type and frequency of WPV., Results: Seventeen participants completed surveys. Verbal abuse by patients was the most often experienced type of WPV. Employees who reported experiencing WPV had higher burnout and lower satisfaction with work and life., Conclusion: WPV routinely occurs in home health care and LTCFs and appears to be related to worker well-being. Facility managers who can control WPV will likely impact the well-being of employees. [ Journal of Gerontological Nursing, 50 (11), 44-52.].

Background: Experiencing symptoms of traumatic stress may be the cost of caring for trauma patients. Emergency nurses caring for trauma patients are at risk for traumatic stress reactions., Objective: This study explored the stress and coping behaviors experienced by emergency nurses who provide trauma care., Methods: Focus groups were held at three urban trauma centers in the Midwestern United States: a Level I pediatric trauma center, a Level I adult trauma center, and a Level III adult trauma center. Data were collected between December 2009 and March 2010. Data analysis was guided by the principles of grounded theory. Line-by-line coding and constant comparative analysis techniques were used to identify recurring constructs., Results: A total of 48 emergency nurses participated. Recurring constructs emerged in the data analysis and coding, revealing four major themes: care of the trauma patient, professional practice, personal life, and support., Conclusions: Nurse job engagement, burnout, and professional and personal relationships are influenced by trauma patient care. The study's resulting themes of care of the trauma patient, professional practice, personal life, and support resulted in the development of the "trauma nursing is a continual experience theory" that can be used as a framework to address these effects. Intentional support and timely interventions based on this new theory can help mitigate the effects of traumatic stress experienced by trauma nurses., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Society of Trauma Nurses.)

Introduction: Establishing research priorities provides focus and direction for limited resources among organizations and increasing impact in a focused area. The Emergency Nurses Association (ENA) Foundation sought to identify research priorities to guide funding decisions in its extramural grants program., Methods: A modified Delphi research strategy was used to build consensus among ENA members and key leaders to determine research focus areas. Two Delphi rounds were conducted. In the first round, 81 emergency nurses participated in providing a list of potential research foci. In the second round, 221 emergency nurse leaders recommended which research topics should be prioritized. Descriptive statistics (frequencies, percentages) were calculated for each research topic. The topics were clustered together and rank ordered by frequency/percentage., Results: Eight research priorities were identified: emergency department overcrowding, workplace violence, nurse well-being, appropriate use of the emergency department, new graduate training, mental health care, disaster training, and diversity, equity, and inclusion research., Discussion: These identified research priorities offer direction for determining ENA Foundation funding priorities. In addition, the research priorities provide strategic direction to emergency nurse researchers to promote a rich depth of research that can make a meaningful impact to science and emergency nursing practice., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

A new Tardigrada species, Claxtonia goni sp. nov. is described from specimens collected in the central area of the Haleakalā National Park, the island of Maui, Hawaii, U.S.A. The new species and Clx. pardalis (Degma Schill, 2015) together with several examples of Clx. wendti (Richters, 1903) are the only known Claxtonia species with the plates having an intracuticular pattern resembling that on a leopard's fur. Claxtonia goni sp. nov. differs from Clx. pardalis in the absence of pores on leg plates, in smaller and uniform pores on dorso-lateral plates, in very unequally spaced teeth in the dentate collar, in lesser ratio of internal cephalic cirrus and lateral cirrus A lengths, and in relatively shorter claws in fourth pair of legs. The differences between the new species and the other congeners as well as Echiniscus species with the same cirri composition and similar cuticular sculpture are also defined. The diagnosis of the genus Claxtonia is amended and three Echiniscus species are transferred into the genus with the proposed new combinations: Claxtonia aliquantilla (Grigarick, Schuster Nelson, 1983) comb. nov., Clx. mosaica (Grigarick, Schuster Nelson, 1983) comb. nov. and Clx. nigripustula (Horning, Schuster Grigarick, 1978) comb. nov..

Specimens of a limnoterrestrial tardigrade collected from moss in New Hampshire, USA and Newfoundland, Canada were identified as belonging to the genus Milnesium. Morphometric data and genetic analysis of the COI gene demonstrated that animals collected from these sites represent the same species. Specimens most closely resemble Milnesium granulatum, a South American species that has been reported also from Great Smoky Mountains National Park (GSMNP), USA. New Hampshire and Newfoundland animals have the same adult claw configuration and cuticular granulation pattern as M. granulatum. Theira* (i.e., normalized to correct for allometric effects) pt values differ from GSMNP M. granulatum in having a more posterior stylet support insertion point. However, all their morphometric values overlap in range with GSMNP specimens. Unlike some other species in the genus, the claw configuration of New Hampshire Milnesium cf. granulatum shows no ontogenetic change in claw configuration. A short (269 bp on average) fragment of the internal transcribed spacer region 2 (ITS-2) was sequenced for 20 New Hampshire adults and from siblings hatched in the laboratory from 8 egg clutches. Genetic diversity among New Hampshire adults was 0.0-3.7%. Multiple haplotypes were found between siblings in a single clutch.

Background: Due to the poor prognosis for advanced renal cell carcinoma (RCC), there is an urgent need for new therapeutic targets and for prognostic markers to identify high risk tumors. MicroRNAs (miRNAs) are frequently dysregulated in tumors, play a crucial role during carcinogenesis and therefore might be promising new biomarkers. In previous studies, we identified miR-141-3p and miR-145-5p to be downregulated in clear cell RCC (ccRCC). Our objective was to investigate the functional association of these miRNAs, focusing on the cooperative regulation of new specific targets and their role in ccRCC progression., Methods: The effect of miR-141-3p and miR-145-5p on cell migration was examined by overexpression in 786-O cells. New targets of both miRNAs were identified by miRWalk, validated in 786-O and ACHN cells and additionally characterized in ccRCC tissue on mRNA and protein level., Results: In functional analysis, a tumor suppressive effect of miR-141-3p and miR-145-5p by decreasing migration and invasion of RCC cells could be shown. Furthermore, co-overexpression of the miRNAs seemed to result in an increased inhibition of cell migration. Both miRNAs were recognized as post-transcriptional regulators of the targets EAPP, HS6ST2, LOX, TGFB2 and VRK2. Additionally, they showed a cooperative effect again as demonstrated by a significantly increased inhibition of HS6ST2 and LOX expression after simultaneous overexpression of both miRNAs. In ccRCC tissue, LOX mRNA expression was strongly increased compared to normal tissue, allowing also to distinguish between non-metastatic and already metastasized primary tumors. Finally, in subsequent tissue microarray analysis LOX protein expression showed a prognostic relevance for the overall survival of ccRCC patients., Conclusion: These results illustrate a jointly strengthening effect of the dysregulated miR-141-3p and miR-145-5p in various tumor associated processes. Focusing on the cooperative effect of miRNAs provides new opportunities for the development of therapeutic strategies and offers novel prognostic and diagnostic capabilities.

The description of Echiniscus cavagnaroi Schuster & Grigarick, 1966 (Tardigrada: Heterotardigrada: Echiniscoidea: Echiniscidae) is emended with new morphometric measurements of the holotype and eleven paratypes. The length of Cirrus A in the holotype (25.2 μm) was only half the 50 μm reported in the original description. Moreover, the largest values for Cirrus A length and Cirrus A to body length ratio for any specimen (40.6 μm, 21%) were also lower than in the original description. Variation in the presence or absence of spines was considerably greater than originally described. Spines C, D d and E were not present on all specimens (C present in 67%, D d in 67%, E in 50%). The length of spines D d and E, when present, varied greatly among specimens. The geographical range of E. cavagnaroi is expanded by new records from the Hawaiian Islands and Bermuda. The species has been reported from southern China; however, the published description of these specimens differs markedly from type specimens in several respects. The presence of E. cavagnaroi sensu stricto in China needs to be confirmed. The high variability in presence or absence and length of spines in Echiniscus cavagnaroi underscores the importance of assessing variability in these characteristics when identifying unknown specimens or describing new species in the genus. This requires using as many specimens as possible and fully reporting variability.

Background: MicroRNAs (miRNAs) regulate gene expression by interfering translation or stability of target transcripts. This interplay between miRNA and their mRNA has been proposed as an important process in cancer development and progression. We have investigated molecular networks impacted by predicted mRNA targets of differentially expressed miRNAs in patients with clear cell renal cell carcinoma (ccRCC) diagnosed with or without metastasis., Material and Methods: miRNA and mRNA microarray expression profiles derived from primary ccRCC from patients with (16 samples) or without diagnosed metastasis (22 samples) were used to identify anti-correlated miRNA-mRNA interaction in ccRCC. For this purpose, Ingenuity pathway analysis microRNA Target Filter, which enables prioritization of experimentally validated and predicted mRNA targets was used. By applying an expression pairing tool, the analysis was focused on targets exhibiting altered expression in our analysis, finding miRNAs and their target genes with opposite or same expression. The resulting identified interactions were revalidated by RT-qPCR in another cohort of ccRCC patients. A selection of the predicted miRNA-mRNA interactions was tested by functional analyses using miRNA knockdown and overexpression experiments in renal cancer cell lines., Results: Among the significantly differentially expressed miRNAs, we have identified three miRNAs (miR-146a-5p, miR-128a-3p, and miR-17-5p) that were upregulated in primary tumors from patients without metastasis and downregulated in primary tumors from patients with metastasis. We have further identified mRNA targets, which expression were inversely correlated to these 3 miRNAs, and have been previously experimentally demonstrated in cancer setting in humans. Specifically, we showed that CXCL8/IL8, UHRF1, MCM10, and CDKN3 were downregulated and targeted by miR-146a-5p. The interaction between miR-146a-5p and their targets CXCL8 and UHRF1 was validated in cell culture experiments., Conclusions: We identified novel target genes of dysregulated miRNAs, which are involved in the transition from primary RCC without metastases into tumors generating distant metastasis.

Integrated analysis of metabolomics, transcriptomics and immunohistochemistry can contribute to a deeper understanding of biological processes altered in cancer and possibly enable improved diagnostic or prognostic tests. In this study, a set of 254 metabolites was determined by gas-chromatography/liquid chromatography-mass spectrometry in matched malignant and non-malignant prostatectomy samples of 106 prostate cancer (PCa) patients. Transcription analysis of matched samples was performed on a set of 15 PCa patients using Affymetrix U133 Plus 2.0 arrays. Expression of several proteins was immunohistochemically determined in 41 matched patient samples and the association with clinico-pathological parameters was analyzed by an integrated data analysis. These results further outline the highly deregulated metabolism of fatty acids, sphingolipids and polyamines in PCa. For the first time, the impact of the ERG translocation on the metabolome was demonstrated, highlighting an altered fatty acid oxidation in TMPRSS2-ERG translocation positive PCa specimens. Furthermore, alterations in cholesterol metabolism were found preferentially in high grade tumors, enabling the cells to create energy storage. With this integrated analysis we could not only confirm several findings from previous metabolomic studies, but also contradict others and finally expand our concepts of deregulated biological pathways in PCa.

Many computer models for predicting the risk of prostate cancer have been developed including for prediction of biochemical recurrence (BCR). However, models for individual BCR free probability at individual time-points after a BCR free period are rare. Follow-up data from 1656 patients who underwent laparoscopic radical prostatectomy (LRP) were used to develop an artificial neural network (ANN) to predict BCR and to compare it with a logistic regression (LR) model using clinical and pathologic parameters, prostate-specific antigen (PSA), margin status (R0/1), pathological stage (pT), and Gleason Score (GS). For individual BCR prediction at any given time after operation, additional ANN, and LR models were calculated every 6 months for up to 7.5 years of follow-up. The areas under the receiver operating characteristic (ROC) curve (AUC) for the ANN (0.754) and LR models (0.755) calculated immediately following LRP, were larger than that for GS (AUC: 0.715; P = 0.0015 and 0.001), pT or PSA (AUC: 0.619; P always <0.0001) alone. The GS predicted the BCR better than PSA (P = 0.0001), but there was no difference between the ANN and LR models (P = 0.39). Our ANN and LR models predicted individual BCR risk from radical prostatectomy for up to 10 years postoperative. ANN and LR models equally and significantly improved the prediction of BCR compared with PSA and GS alone. When the GS and ANN output values are combined, a more accurate BCR prediction is possible, especially in high-risk patients with GS ≥7.

This paper provides a comprehensive list of the freshwater and terrestrial tardigrade fauna reported from the Americas (North America, South America, Central America and the West Indies), their distribution in the Americas, and the substrates from which they have been reported. Data were obtained from 316 published references. Authors' identifications were accepted at face value unless subsequently amended. Taxa were assigned to sub-national units (states, provinces, etc.). Many areas, in particular large portions of Central America and the West Indies, have no reported tardigrade fauna.        The presence of 54 genera and 380 species has been reported for the Americas; 245 species have been collected in the Nearctic ecozone and 251 in the Neotropical ecozone. Among the tardigrade species found in the Americas, 52 are currently considered cosmopolitan, while 153 species have known distributions restricted to the Americas. Based on recent taxonomic revision of the genus Milnesium, the vast majority of records of M. tardigradum in the Americas should now be reassigned to Milnesium tardigradum sensu lato, either because the provided description differs from M. tardigradum sensu stricto or because insufficient description is provided to make a determination; the remainder should be considered Milnesium cf. tardigradum.        Most terrestrial tardigrade sampling in the Americas has focused on cryptogams (mosses, lichens and liverworts); 90% of the species have been collected in such substrates. The proportion of species collected in other habitats is lower: 14% in leaf litter, 20% in soil, and 24% in aquatic samples (in other terrestrial substrates the proportion never exceeds 5%). Most freshwater tardigrades have been collected from aquatic vegetation and sediment. For nine species in the Americas no substrates have been reported.

Bladder cancer is a common cancer in the Western world. The current prognosticators such as tumor grade, stage, size, and multifocality do not accurately reflect the clinical outcome. It is of clinical interest to identify biomarkers that could improve diagnostic and/or prognostic predictions. The objectives of this study were to identify deregulated miRNAs in bladder cancer samples and evaluate their potential as diagnostic and prognostic biomarkers. We screened 723 miRNAs by microarray and selected a subset of 15 distinctively deregulated miRNAs for further validation by real-time quantitative RT-(q)PCR. Seven miRNAs (miR-20a, miR-106b, miR-130b, miR-141, miR-200a, miR-200a*, and miR-205) were found to be up-regulated and eight miRNAs (miR-100, miR-125b, miR-130a, miR-139-5p, miR-145*, miR-199a-3p, miR-214, and miR-222) were found to be down-regulated in malignant bladder tissue samples compared to healthy tissue. Four miRNAs that have already been described in the literature (miR-141, miR-199a-3p, miR-205, and miR-214) were significantly differentially expressed between nonmuscle-invasive and muscle-invasive bladder cancer. Furthermore, real-time RT-qPCR of all miRNAs provided high overall correct classification (>75%) of bladder cancer diagnosis. Two miRNAs (miR-141 and miR-205) were associated with overall survival time. The verification of tumor-specific miRNA expression profile, together with the observed association of miR-141 and miR-205 expression with overall survival, underline the potential of miRNAs to function as diagnostic and/or prognostic markers of bladder cancer., (Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. It has been proposed that miRNAs play an important role in cancer development and progression. Their ability to affect multiple gene pathways by targeting various mRNAs makes them an interesting class of regulators., Methodology/principal Findings: We have developed an algorithm, Classification based Analysis of Paired Expression data of RNA (CAPE RNA), which is capable of identifying altered miRNA-mRNA regulation between tissues samples that assigns interaction states to each sample without preexisting stratification of groups. The distribution of the assigned interaction states compared to given experimental groups is used to assess the quality of a predicted interaction. We demonstrate the applicability of our approach by analyzing urothelial carcinoma and normal bladder tissue samples derived from 24 patients. Using our approach, normal and tumor tissue samples as well as different stages of tumor progression were successfully stratified. Also, our results suggest interesting differentially regulated miRNA-mRNA interactions associated with bladder tumor progression., Conclusions/significance: The need for tools that allow an integrative analysis of microRNA and mRNA expression data has been addressed. With this study, we provide an algorithm that emphasizes on the distribution of samples to rank differentially regulated miRNA-mRNA interactions. This is a new point of view compared to current approaches. From bootstrapping analysis, our ranking yields features that build strong classifiers. Further analysis reveals genes identified as differentially regulated by miRNAs to be enriched in cancer pathways, thus suggesting biologically interesting interactions.

The pathogenesis of allergic airway inflammation and disease is complex and still not fully understood. Many cells, factors and mediators are involved in the different aspects of induction, maintenance and persistence of airway inflammation. The heterogeneity and redundancy of this system is one of the main reasons why novel therapeutic targets focusing on the pathogenesis of asthma only hesitantly reach the market and clinical application. Thus, it seems mandatory that we proceed in our efforts to better understand this micro cosmos to succeed in the development of safe and effective drugs for the treatment of more severe and refractory forms of asthma and chronic obstructive pulmonary disease. One of the more recently discovered mediators in the context of airway inflammation are the lipocalins (Lcns). They are a family of proteins that share functional and structural similarities and are involved in the transport of small hydrophobic molecules such as steroids and lipids into the cell. Lcns are found in many different cell types from plants and bacteria through invertebrate cells to cells of vertebrate origin. The purpose of this review is to summarize the role of Lcns in airway diseases, focusing on allergic and infectious inflammation. In particular, we will summarize the present knowledge about Lipocalin 1 and Lipocalin 2, where exciting new discoveries in the recent years have highlighted their role in pulmonary disease and infection. This new class of proteins is another putative candidate for the development of novel drugs against airway inflammation., (© 2012 Blackwell Publishing Ltd.)

Artificial neural networks (ANNs) are mathematical models that are based on biological neural networks and are composed of interconnected groups of artificial neurons. ANNs are used to map and predict outcomes in complex relationships between given 'inputs' and sought-after 'outputs' and can also be used find patterns in datasets. In medicine, ANN applications have been used in cancer diagnosis, staging and recurrence prediction since the mid-1990s, when an enormous effort was initiated, especially in prostate cancer detection. Modern ANNs can incorporate new biomarkers and imaging data to improve their predictive power and can offer a number of advantages as clinical decision making tools, such as easy handling of distribution-free input parameters. Most importantly, ANNs consider nonlinear relationships among input data that cannot always be recognized by conventional analyses. In the future, complex medical diagnostic and treatment decisions will be increasingly based on ANNs and other multivariate models.

Background: We compared urinary prostate cancer antigen 3 (PCA3), transmembrane protease, serine 2 (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) gene fusion (T2:ERG), and the serum [-2]proprostate-specific antigen ([-2]proPSA)-based prostate health index (Phi) for predicting biopsy outcome., Methods: Serum samples and first-catch urine samples were collected after digital rectal examination (DRE) from consented outpatients with PSA 0.5-20 μg/L who were scheduled for prostate biopsy. The PCA3 score (PROGENSA PCA3, Hologic Gen-Probe) and T2:ERG score (Hologic Gen-Probe) were determined. Measurements of serum PSA, free PSA, and [-2]proPSA (Beckman Coulter) were performed, and the percentages of free PSA (%fPSA) and Phi ([-2]proPSA/fPSA × √PSA) were determined., Results: Of 246 enrolled men, prostate cancer (PCa) was diagnosed in 110 (45%) and there was no evidence of malignancy (NEM) in 136 (55%). A first set of biopsies was performed in 136 (55%) of all men, and 110 (45%) had ≥1 repeat biopsies. PCA3, Phi, and T2:ERG differed significantly between men with PCa and NEM, and these markers showed the largest areas under the ROC curve (AUCs) (0.74, 0.68, and 0.63, respectively). PCA3 had the largest AUC of all parameters, albeit not statistically different from Phi. Phi showed somewhat lower specificities than PCA3 at 90% sensitivity. Combination of both markers enhanced diagnostic power with modest AUC gains of 0.01-0.04. Although PCA3 had the highest AUC in the repeat-biopsy cohort, the highest AUC for Phi was observed in DRE-negative patients with PSA in the 2-10 μg/L range., Conclusions: PCA3 and Phi were superior to the other evaluated parameters but their combination gave only moderate enhancements in diagnostic accuracy for PCa at first or repeat prostate biopsy., (© 2012 American Association for Clinical Chemistry)

Purpose: Limited data exist on the relationship of percent free prostate specific antigen and prostate specific antigen density with prostate cancer prognosis. Therefore, we compared percent free prostate specific antigen and prostate specific antigen density with prostate specific antigen, Gleason sum and stage to predict prostate cancer prognosis in a large cohort using a single prostate specific antigen and free prostate specific antigen assay., Materials and Methods: Between 1999 and 2007 a total of 1,656 patients with prostate cancer underwent laparoscopic radical prostatectomy at the Charité Berlin. There were 322 patients excluded from analysis for a variety of reasons. The final 1,334 patients had prostate specific antigen, free prostate specific antigen, prostate volume and complete pathological analysis available., Results: Median followup was 60.3 months (range 0.2 to 135). Median age (63 years, range 43 to 75) did not differ between the 1,092 patients without and the 242 with biochemical recurrence (p = 0.956), but prostate volume, prostate specific antigen and percent free prostate specific antigen differed significantly (p <0.0001). While prostate specific antigen and prostate specific antigen density increased significantly in patients with Gleason less than 7, 7 and greater than 7 tumors, percent free prostate specific antigen decreased significantly (p <0.0001). Prostate specific antigen, percent free prostate specific antigen and prostate specific antigen density differed significantly between pT2 and pT3 tumors, and between patients with vs without positive surgical margins. On univariate analysis Gleason sum, pathological stage, positive surgical margin, total prostate specific antigen, percent free prostate specific antigen and prostate specific antigen density were predictors of biochemical recurrence-free survival. Multivariate Cox regression analysis identified Gleason sum, pathological stage, positive surgical margin and prostate specific antigen density as independent predictors of biochemical recurrence-free survival, while percent free prostate specific antigen and total prostate specific antigen failed to be significant., Conclusions: Few models for prostate cancer prognosis include prostate specific antigen density. There is substantial value in prostate specific antigen density but not in percent free prostate specific antigen for improving prostate cancer prognosis and biochemical recurrence prediction., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)