Iodine Brachytherapy for Large Uveal Melanomas

Uveal melanoma is the most common primary intraocular malignancy in adults. Vision in the affected eye is threatened by both the tumor and side-effects from the treatments currently available. Poor prognosis for saving vision increases with tumor size and, consequently, enucleation has been the treatment of choice for large uveal melanomas in most centers. However, increasing evidence suggests that no survival benefit is gained (nor lost) by enucleation as compared to eye-conserving methods. The Helsinki University Eye Hospital has since 1990 offered episcleral iodine-125 plaque brachytherapy (IBT) for all patients unwilling to undergo enucleation for a large uveal melanoma. The primary aim of this study was to assess survival, local tumor recurrence and preservation of the eye and vision after IBT in a population-based series of 97 patients with uveal melanomas classified as large by the Collaborative Ocular Melanoma Study (COMS) criteria. Further aims included reporting the incidence of side-effects and assessing the role of intraocular dose distribution and clinical risk factors in their development. Finally, means to improve the current treatment were investigated by using computer models to compare existing plaques with collimating ones and by comparing the outcome of a subgroup of 54 IBT patients with very thick tumors with 33 patients with similarly-sized tumors managed with transscleral local resection (TSR) in Liverpool, United Kingdom. Kaplan-Meier estimates of all-cause and melanoma-specific survival at 5 years after IBT were 62% and 65%, respectively, and visually comparable with the survival experience of patients reported after enucleation by the COMS. Local recurrence developed in 6% of eyes and 84% of eyes were conserved at 5 years. Visual prognosis was guarded with 11% avoiding loss of 20/70 vision and 26% avoiding loss of 20/400 vision in the tumor eye at 2 years. Large tumor height and short distance from the posterior pole were independently associated with loss of vision. Using cumulative incidence analysis to account for competing risks, such as enucleation and metastatic death, the 5-year incidence of cataract after IBT was 79%, glaucoma 60%, optic neuropathy 46%, maculopathy 52%, persistent or recurring retinal detachment (RD) 25%, and vitreous hemorrhage 36%. In multivariate competing risks regression models, increasing tumor height was associated with cataract, iris neovascularization and RD. Maculopathy and optic neuropathy were associated with distance from the tumor to the respective structure. Median doses to the tumor apex, macula and optic disc were 81 Gy (range, 40-158), 79 Gy (range, 12-632), and 83 Gy (range, 10-377), respectively. Dose to the optic disc was independently associated with optic neuropathy, and both dose to the optic disc and dose to the macula predicted vision loss after IBT. Simulated treatment using collimating plaques resulted in clinically meaningful reduction in both optic disc (median reduction, 30 Gy) and macular (median reduction, 36 Gy) doses as compared to the actual treatment with standard plaques. In the subgroup of patients with uveal melanomas classified as large because of tumor height, cumulative incidence analysis revealed that while long-term preservation of 20/70 vision was rare after both IBT and TSR, preservation of 20/400 vision was better after TSR (32% vs. 5% at 5 years). In multivariate logistic regression models, TSR was independently associated with better preservation of 20/400 vision (OR 0.03 at 2 years, P=0.005) No cases of secondary glaucoma were observed after TSR and optic neuropathy was rare. However, local tumor recurrence was more common after TSR than it was after IBT (Cumulative incidence 41% vs. 7% at 5 years, respectively). In terms of survival, IBT seems to be a safe alternative to enucleation in managing large uveal melanomas. Local tumor control is no worse than with medium-sized tumors and the chances of avoiding secondary enucleation are good. Unfortunately, side-effects from radiotherapy are frequent, especially in thick tumors, and long-term prognosis of saving vision is consequently guarded. Some complications can be limited by using collimating plaques and by managing uveal melanomas that are large because of tumor height with TSR instead of IBT. However, the patient must be willing to accept a substantial risk of local tumor recurrence after TSR and it is best suited for cases in which the preservation of vision in the tumor eye is critical.

Low-impact Use: A New Standard

Once the ugly duckling of the lighting world, the fluorescent bulb recently has become something of an eco-darling thanks to its energy efficiency. Whereas a standard off-the-shelf incandescent bulb devotes only about five percent of its total electrical consumption to produce visible light (the remainder is released in heat), fluorescent lighting employs an entirely different process (it radiates rather than burns) that is four to six times more efficient. Fluorescents are indisputably superior in ­performance, but up to 5 milligrams of mercury, a hazardous trace metal, is included in the manufacture of each lamp

New approximation algorithms for minimum cycle bases of graphs

We consider the problem of computing an approximate minimum cycle basis of an undirected edge-weighted graph G with m edges and n vertices; the extension to directed graphs is also discussed. In this problem, a {0,1} incidence vector is associated with each cycle and the vector space over F-2 generated by these vectors is the cycle space of G. A set of cycles is called a cycle basis of G if it forms a basis for its cycle space. A cycle basis where the sum of the weights of the cycles is minimum is called a minimum cycle basis of G. Cycle bases of low weight are useful in a number of contexts, e.g. the analysis of electrical networks, structural engineering, chemistry, and surface reconstruction. We present two new algorithms to compute an approximate minimum cycle basis. For any integer k >= 1, we give (2k - 1)-approximation algorithms with expected running time 0(kmn(1+2/k) + mn((1+1/k)(omega-1))) and deterministic running time 0(n(3+2/k)), respectively. Here omega is the best exponent of matrix multiplication. It is presently known that omega < 2.376. Both algorithms are o(m(omega)) for dense graphs. This is the first time that any algorithm which computes sparse cycle bases with a guarantee drops below the Theta(m(omega)) bound. We also present a 2-approximation algorithm with O(m(omega) root n log n) expected running time, a linear time 2-approximation algorithm for planar graphs and an O(n(3)) time 2.42-approximation algorithm for the complete Euclidean graph in the plane.

Visual performance at passive level crossings with long sighting distances

The third edition of the Australian Standard AS1742 Manual of Uniform Traffic Control Devices Part 7 provides a method of calculating the sighting distance required to safely proceed at passive level crossings based on the physics of moving vehicles. This required distance becomes greater with higher line speeds and slower, heavier vehicles so that it may return quite a long sighting distance. However, at such distances, there are also concerns around whether drivers would be able to reliably identify a train in order to make an informed decision regarding whether it would be safe to proceed across the level crossing. In order to determine whether drivers are able to make reliable judgements to proceed in these circumstances, this study assessed the distance at which a train first becomes identifiable to a driver as well as their, ability to detect the movement of the train. A site was selected in Victoria, and 36 participants with good visual acuity observed 4 trains in the 100-140 km/h range. While most participants could detect the train from a very long distance (2.2 km on average), they could only detect that the train was moving at much shorter distances (1.3 km on average). Large variability was observed between participants, with 4 participants consistently detecting trains later than other participants. Participants tended to improve in their capacity to detect the presence of the train with practice, but a similar trend was not observed for detection of the movement of the train. Participants were consistently poor at accurately judging the approach speed of trains, with large underestimations at all investigated distances.

Trust and Safe Choices: Coping with health-related risks in food consumption in St. Petersburg

This dissertation considers the problem of trust in the context of food consumption. The research perspectives refer to institutional conditions for consumer trust, personal practices of food consumption, and strategies consumers employ for controlling the safety of their food. The main concern of the study is to investigate consumer trust as an adequate response to food risks, i.e. a strategy helping the consumer to make safe choices in an uncertain food situation. "Risky" perspective serves as a frame of reference for understanding and explaining trust relations. The original aim of the study was to reveal the meanings applied to the concepts of trust, safety and risks in the perspective of market choices, the assessments of food risks and the ways of handling them. Supplementary research tasks presumed descriptions of institutional conditions for consumer trust, including descriptions of the food market, and the presentation of food consumption patterns in St. Petersburg. The main empirical material is based on qualitative interviews with consumers and interviews and group discussions with professional experts (market actors, representatives of inspection bodies and consumer organizations). Secondary material is used for describing institutional conditions for consumer trust and the market situation. The results suggest that the idea of consumer trust is associated with the reputation of suppliers, stable quality and taste of their products, and reliable food information. Being a subjectively constructed state connected to the act of acceptance, consumer trust results in positive buying decisions and stable preferences in the food market. The consumers' strategies that aim at safe food choices refer to repetitive interactions with reliable market actors that free them from constant consideration in the marketplace. Trust in food is highly mediated by trust in institutions involved in the food system. The analysis reveals a clear pattern of disbelief in the efficiency of institutional food control. The study analyses this as a reflection of "total distrust" that appears to be a dominant mood in many contexts of modern Russia. However, the interviewees emphasize the state's decisive role in suppressing risks in the food market. Also, the findings are discussed with reference to the consumers' possibilities of personal control over food risks. Three main responses to a risky food situation are identified: the reflexive approach, the traditional approach, and the fatalistic approach.

Search for the associated production of the standard-model Higgs boson in the all-hadronic channel

"We report on a search for the standard-model Higgs boson in pp collisions at s=1.96 TeV using an integrated luminosity of 2.0 fb(-1). We look for production of the Higgs boson decaying to a pair of bottom quarks in association with a vector boson V (W or Z) decaying to quarks, resulting in a four-jet final state. Two of the jets are required to have secondary vertices consistent with B-hadron decays. We set the first 95% confidence level upper limit on the VH production cross section with V(-> qq/qq('))H(-> bb) decay for Higgs boson masses of 100-150 GeV/c(2) using data from run II at the Fermilab Tevatron. For m(H)=120 GeV/c(2), we exclude cross sections larger than 38 times the standard-model prediction."

Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode

We combine searches by the CDF and D0 collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb-1 of p-pbar collisions at sqrt{s}=1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard-model Higgs boson in the mass range 162-166 GeV at the 95% C.L.

Inclusive Search for Standard Model Higgs Boson Production in the WW Decay Channel using the CDF II Detector

We present a search for standard model (SM) Higgs boson production using ppbar collision data at sqrt(s) = 1.96 TeV, collected with the CDF II detector and corresponding to an integrated luminosity of 4.8 fb-1. We search for Higgs bosons produced in all processes with a significant production rate and decaying to two W bosons. We find no evidence for SM Higgs boson production and place upper limits at the 95% confidence level on the SM production cross section (sigma(H)) for values of the Higgs boson mass (m_H) in the range from 110 to 200 GeV. These limits are the most stringent for m_H > 130 GeV and are 1.29 above the predicted value of sigma(H) for mH = 165 GeV.

Search for the associated production of the standard-model Higgs boson in the all-hadronic channel

"We report on a search for the standard-model Higgs boson in pp collisions at s=1.96 TeV using an integrated luminosity of 2.0 fb(-1). We look for production of the Higgs boson decaying to a pair of bottom quarks in association with a vector boson V (W or Z) decaying to quarks, resulting in a four-jet final state. Two of the jets are required to have secondary vertices consistent with B-hadron decays. We set the first 95% confidence level upper limit on the VH production cross section with V(-> qq/qq('))H(-> bb) decay for Higgs boson masses of 100-150 GeV/c(2) using data from run II at the Fermilab Tevatron. For m(H)=120 GeV/c(2), we exclude cross sections larger than 38 times the standard-model prediction."

Search for standard model Higgs boson production in association with a W boson using a neural network discriminant at CDF

We present a search for standard model Higgs boson production in association with a W boson in proton-antiproton collisions at a center of mass energy of 1.96 TeV. The search employs data collected with the CDF II detector that correspond to an integrated luminosity of approximately 1.9 inverse fb. We select events consistent with a signature of a single charged lepton, missing transverse energy, and two jets. Jets corresponding to bottom quarks are identified with a secondary vertex tagging method, a jet probability tagging method, and a neural network filter. We use kinematic information in an artificial neural network to improve discrimination between signal and background compared to previous analyses. The observed number of events and the neural network output distributions are consistent with the standard model background expectations, and we set 95% confidence level upper limits on the production cross section times branching fraction ranging from 1.2 to 1.1 pb or 7.5 to 102 times the standard model expectation for Higgs boson masses from 110 to $150 GeV/c^2, respectively.

Searching the inclusive ℓγE̸T+b-quark signature for radiative top quark decay and non-standard-model processes

In a search for new phenomena in a signature suppressed in the standard model of elementary particles (SM), we compare the inclusive production of events containing a lepton, a photon, significant transverse momentum imbalance (MET), and a jet identified as containing a b-quark, to SM predictions. The search uses data produced in proton-antiproton collisions at 1.96 TeV corresponding to 1.9 fb-1 of integrated luminosity taken with the CDF detector at the Fermilab Tevatron. We find 28 lepton+photon+MET+b events versus an expectation of 31.0+4.1/-3.5 events. If we further require events to contain at least three jets and large total transverse energy, simulations predict that the largest SM source is top-quark pair production with an additional radiated photon, ttbar+photon. In the data we observe 16 ttbar+photon candidate events versus an expectation from SM sources of 11.2+2.3/-2.1. Assuming the difference between the observed number and the predicted non-top-quark total is due to SM top quark production, we estimate the ttg cross section to be 0.15 +- 0.08 pb.

Potential functions for hydrogen bond interactions - IV. Minimum Energy Conformation of the α-Helical Structure of PoIy-L-Alanine

Making use of the empirical potential functions for peptide NH .. O bonds, developed in this laboratory, the relative stabilities of the rightand left-handed α-helical structures of poly-L-alanine have been investigated, by calculating their conformational energies (V). The value of Vmin of the right-handed helix (αP) is about - 10.4 kcal/mole, and that of the left-handed helix (αM) is about - 9.6 kcal/mole, showing that the former is lower in energy by 0.8 kcal/mole. The helical parameters of the stable conformation of αP are n ∼ 3.6 and h ∼ 1.5 Å. The hydrogen bond of length 2.85 Å and nonlinearity of about 10° adds about 4.0 kcal/ mole to the stabilising energy of the helix in the minimum enregy region. The energy minimum is not sharply defined, but occurs over a long valley, suggesting that a distribution of conformations (φ{symbol}, ψ) of nearly the same energy may occur for the individual residues in a helix. The experimental data of a-helical fibres of poly-L-alanine are in good agreement with the theoretical results for αP. In the case of proteins, the mean values of (φ{symbol}, ψ) for different helices are distributed, but they invariably occur within the contour for V = Vmin + 2 kcal/mole for αP.

Method for obtaining minimum noise in a general purpose hot wire amplifier

It has been shown that the conventional practice of designing a compensated hot wire amplifier with a fixed ceiling to floor ratio results in considerable and unnecessary increase in noise level at compensation settings other than optimum (which is at the maximum compensation at the highest frequency of interest). The optimum ceiling to floor ratio has been estimated to be between 1.5-2.0 ωmaxM. Application of the above considerations to an amplifier in which the ceiling to floor ratio is optimized at each compensation setting (for a given amplifier band-width), shows the usefulness of the method in improving the signal to noise ratio.

A Safe Vaccine (DV-STM-07) against Salmonella Infection Prevents Abortion and Confers Protective Immunity to the Pregnant and New Born Mice

Pregnancy is a transient immuno-compromised condition which has evolved to avoid the immune rejection of the fetus by the maternal immune system. The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination. Active vaccination during pregnancy may lead to abortion induced by heightened cell mediated immune response. In this study, we have administered the highly attenuated vaccine strain delta pmrG-HM-D (DV-STM-07) in female mice before the onset of pregnancy and followed the immune reaction against challenge with virulent S. Typhimurium in pregnant mice. Here we demonstrate that DV-STM-07 vaccine gives protection against Salmonella in pregnant mice and also prevents Salmonella induced abortion. This protection is conferred by directing the immune response towards Th2 activation and Th1 suppression. The low Th1 response prevents abortion. The use of live attenuated vaccine just before pregnancy carries the risk of transmission to the fetus. We have shown that this vaccine is safe as the vaccine strain is quickly eliminated from the mother and is not transmitted to the fetus. This vaccine also confers immunity to the new born mice of vaccinated mothers. Since there is no evidence of the vaccine candidate reaching the new born mice, we hypothesize that it may be due to trans-colostral transfer of protective anti-Salmonella antibodies. These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born. Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.