Hybrid time-domain and continuous-wave diffuse optical tomography instrument with concurrent, clinical magnetic resonance imaging for breast cancer imaging

Diffuse optical tomography has demonstrated significant potential for clinical utility in the diagnosis and prognosis of breast cancer, and its use in combination with other structural imaging modalities improves lesion localization and the quantification of functional tissue properties. Here, we introduce a hybrid diffuse optical imaging system that operates concurrently with magnetic resonance imaging (MRI) in the imaging suite, utilizing commercially available MR surface coils. The instrument acquires both continuous-wave and time-domain diffuse optical data in the parallel-plate geometry, permitting both absolute assignment of tissue optical properties and three-dimensional tomography; moreover, the instrument is designed to incorporate diffuse correlation spectroscopic measurements for probing tissue blood flow. The instrument is described in detail here. Image reconstructions of a tissue phantom are presented as an initial indicator of the system's ability to accurately reconstruct optical properties and the concrete benefits of the spatial constraints provided by concurrent MRI. Last, we briefly discuss how various data combinations that the instrument could facilitate, including tissue perfusion, can enable more comprehensive assessment of lesion physiology

Structural Insights into Triglyceride Storage Mediated by Fat Storage-Inducing Transmembrane (FIT) Protein 2

Fat storage-Inducing Transmembrane proteins 1 & 2 (FIT1/FITM1 and FIT2/FITM2) belong to a unique family of evolutionarily conserved proteins localized to the endoplasmic reticulum that are involved in triglyceride lipid droplet formation. FIT proteins have been shown to mediate the partitioning of cellular triglyceride into lipid droplets, but not triglyceride biosynthesis. FIT proteins do not share primary sequence homology with known proteins and no structural information is available to inform on the mechanism by which FIT proteins function. Here, we present the experimentally-solved topological models for FIT1 and FIT2 using N-glycosylation site mapping and indirect immunofluorescence techniques. These methods indicate that both proteins have six-transmembrane-domains with both N- and C-termini localized to the cytosol. Utilizing this model for structure-function analysis, we identified and characterized a gain-of-function mutant of FIT2 (FLL(157-9)AAA) in transmembrane domain 4 that markedly augmented the total number and mean size of lipid droplets. Using limited-trypsin proteolysis we determined that the FLL(157-9)AAA mutant has enhanced trypsin cleavage at K86 relative to wild-type FIT2, indicating a conformational change. Taken together, these studies indicate that FIT2 is a 6 transmembrane domain-containing protein whose conformation likely regulates its activity in mediating lipid droplet formation

Menstrual function among women exposed to polybrominated biphenyls: A follow-up prevalence study

BACKGROUND: Alteration in menstrual cycle function is suggested among rhesus monkeys and humans exposed to polybrominated biphenyls (PBBs) and structurally similar polychlorinated biphenyls (PCBs). The feedback system for menstrual cycle function potentially allows multiple pathways for disruption directly through the hypothalamic-pituitary-ovarian axis and indirectly through alternative neuroendocrine axes. METHODS: The Michigan Female Health Study was conducted during 1997–1998 among women in a cohort exposed to PBBs in 1973. This study included 337 women with self-reported menstrual cycles of 20–35 days (age range: 24–56 years). Current PBB levels were estimated by exponential decay modeling of serum PBB levels collected from 1976–1987 during enrollment in the Michigan PBB cohort. Linear regression models for menstrual cycle length and the logarithm of bleed length used estimated current PBB exposure or enrollment PBB exposure categorized in tertiles, and for the upper decile. All models were adjusted for serum PCB levels, age, body mass index, history of at least 10% weight loss in the past year, physical activity, smoking, education, and household income. RESULTS: Higher levels of physical activity were associated with shorter bleed length, and increasing age was associated with shorter cycle length. Although no overall association was found between PBB exposure and menstrual cycle characteristics, a significant interaction between PBB exposures with past year weight loss was found. Longer bleed length and shorter cycle length were associated with higher PBB exposure among women with past year weight loss. CONCLUSION: This study suggests that PBB exposure may impact ovarian function as indicated by menstrual cycle length and bleed length. However, these associations were found among the small number of women with recent weight loss suggesting either a chance finding or that mobilization of PBBs from lipid stores may be important. These results should be replicated with larger numbers of women exposed to similar lipophilic compounds

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Lessons from a one-year hospital-based surveillance of acute respiratory infections in Berlin- comparing case definitions to monitor influenza

<p>Abstract</p> <p>Background</p> <p>Surveillance of severe acute respiratory infections (SARI) in sentinel hospitals is recommended to estimate the burden of severe influenza-cases. Therefore, we monitored patients admitted with respiratory infections (RI) in 9 Berlin hospitals from 7.12.2009 to 12.12.2010 according to different case definitions (CD) and determined the proportion of cases with influenza A(H1N1)pdm09 (pH1N1). We compared the sensitivity and specificity of CD for capturing pandemic pH1N1 cases.</p> <p>Methods</p> <p>We established an RI-surveillance restricted to adults aged ≤ 65 years within the framework of a pH1N1 vaccine effectiveness study, which required active identification of RI-cases. The hospital information-system was screened daily for newly admitted RI-patients. Nasopharyngeal swabs from consenting patients were tested by PCR for influenza-virus subtypes. Four clinical CD were compared in terms of capturing pH1N1-positives among hospitalized RI-patients by applying sensitivity and specificity analyses. The broadest case definition (CD1) was used for inclusion of RI-cases; the narrowest case definition (CD4) was identical to the SARI case definition recommended by ECDC/WHO.</p> <p>Results</p> <p>Over the study period, we identified 1,025 RI-cases, of which 283 (28%) met the ECDC/WHO SARI case definition. The percentage of SARI-cases among internal medicine admissions decreased from 3.2% (calendar-week 50-2009) to 0.2% (week 25-2010). Of 354 patients tested by PCR, 20 (6%) were pH1N1-positive. Two case definitions narrower than CD1 but -in contrast to SARI- not requiring shortness of breath yielded the largest areas under the Receiver-Operator-Curve. Heterogeneity of proportions of patients admitted with RI between hospitals was significant.</p> <p>Conclusions</p> <p>Comprehensive surveillance of RI cases was feasible in a network of community hospitals. In most settings, several hospitals should be included to ensure representativeness. Although misclassification resulting from failure to obtain symptoms in the hospital information-system cannot be ruled out, a high proportion of hospitalized PCR-positive pH1N1-patients (45%) did not fulfil the SARI case-definition that included shortness of breath or difficulty breathing. Thus, to assess influenza-related disease burden in hospitals, broader, alternative case definitions should be considered.</p

Spatial and Temporal Trends of Global Pollination Benefit

Pollination is a well-studied and at the same time a threatened ecosystem service. A significant part of global crop production depends on or profits from pollination by animals. Using detailed information on global crop yields of 60 pollination dependent or profiting crops, we provide a map of global pollination benefits on a 5′ by 5′ latitude-longitude grid. The current spatial pattern of pollination benefits is only partly correlated with climate variables and the distribution of cropland. The resulting map of pollination benefits identifies hot spots of pollination benefits at sufficient detail to guide political decisions on where to protect pollination services by investing in structural diversity of land use. Additionally, we investigated the vulnerability of the national economies with respect to potential decline of pollination services as the portion of the (agricultural) economy depending on pollination benefits. While the general dependency of the agricultural economy on pollination seems to be stable from 1993 until 2009, we see increases in producer prices for pollination dependent crops, which we interpret as an early warning signal for a conflict between pollination service and other land uses at the global scale. Our spatially explicit analysis of global pollination benefit points to hot spots for the generation of pollination benefits and can serve as a base for further planning of land use, protection sites and agricultural policies for maintaining pollination services

The Global Burden of Alveolar Echinococcosis

Human alveolar echinococcosis (AE), caused by the larval stage of the fox tapeworm Echinococcus multilocularis, is amongst the world's most dangerous zoonoses. Transmission to humans is by consumption of parasite eggs which are excreted in the faeces of the definitive hosts: foxes and, increasingly, dogs. Transmission can be through contact with the definitive host or indirectly through contamination of food or possibly water with parasite eggs. We made an intensive search of English, Russian, Chinese and other language databases. We targeted data which could give country specific incidence or prevalence of disease and searched for data from every country we believed to be endemic for AE. We also used data from other sources (often unpublished). From this information we were able to make an estimate of the annual global incidence of disease and disease burden using standard techniques for calculation of DALYs. Our studies suggest that AE results in a median of 18,235 cases globally with a burden of 666,433 DALYs per annum. This is the first estimate of the global burden of AE both in terms of global incidence and DALYs and demonstrates the burden of AE is comparable to several diseases in the neglected tropical disease cluster

Serotonin synthesis, release and reuptake in terminals: a mathematical model

<p>Abstract</p> <p>Background</p> <p>Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system.</p> <p>Methods</p> <p>We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data.</p> <p>Results</p> <p>We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct <it>in silico </it>experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine.</p> <p>Conclusions</p> <p>Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.</p

Assessing the Effects of Responsible Leadership and Ethical Conflict on Behavioral Intention

[[abstract]]This study develops a research model that elaborates how responsible leadership and ethical conflict influence employees from the perspectives of role theory and attachment theory. Its empirical results reveal that turnover intention indirectly relates to ethical conflict and responsible leadership via the mediating mechanisms of organizational identification and organizational uncertainty. At the same time, helping intention indirectly relates to ethical conflict and responsible leadership only through organizational identification. Finally, the managerial implications for international business and research limitations based on the empirical results are discussed.[[notice]]補正完