A comparison of two methods for segmentation of functional volumes in radiotherapy planning of lung cancer patients.

BACKGROUND: In radiotherapy (RT) of lung cancer, dose to functional lung (FL) volumes segmented with two different methods (perfusion SPECT (Q-SPECT) and 4D-CT (4D) ventilation (V)) have been shown to correlate with the incidence of radiation pneumonitis (RP). This study aims to compare the FL volumes identified by both methods. MATERIAL AND METHODS: Thirty lung cancer patients had a 4D and Q-SPECT prior to treatment. Seventeen of these patients also had a ventilation SPECT (V-SPECT). FL sub-volumes were segmented automatically, using cut-off values. The volumes were compared in terms of overlap fraction (OF) relative to the minimal volume, and intersection fraction (IF) of the FL volume relative to the total lung volume (VLung). RESULTS: Cut-off values suggested in literature for Q-SPECT and 4D-V resulted in volumes differing in size by a median 18% [6%;31%], and a median OF and IF of 0.48 [0.23;0.70] and 0.09 [0.02;0.25], respectively. Segmenting volumes of comparable size of about 1/3 of VLung (FL-m(1/3), m = method) resulted in a median OF and IF of 0.43 [0.23;0.58] and 0.12 [0.06;0.19], respectively. Twenty-five patients (83%) had a reasonable overlap between FL-Q(1/3) and FL-4D-V(1/3) volumes, with OF values above 0.33. IF increased significantly (p = .036) compared to using fixed cut-off values. Similarly, volumes of comparable size of about 1/3 VLung were produced for V-SPECT, and FL-Q(1/3), FL-V(1/3), and FL-4D-V(1/3) were compared. The overlaps and intersections of FL-V(1/3) with FL-Q(1/3) volumes were significantly (p<.001) larger than the corresponding overlaps and intersections of FL-Q(1/3) with FL-4D(1/3) and FL-V(1/3) with FL-4D(1/3). CONCLUSION: The Q-SPECT and 4D-V methods do not segment entirely the same FL volumes. A reasonable overlap of the volumes along with the findings of other studies that both correlate to RP incidence, suggests that a combination of both volumes, e.g. using the IF, may be useful in RT treatment planning.

Mineral magnetic measurements as a pollution proxy for canal sediments (Birmingham Canal Navigation Main Line).

The use of mineral magnetic measurements (XLF, XARM and saturation isothermal remanent magnetization (SIRM)) as a potential particle size - pollution proxy for sediment samples collected from the Birmingham Mainline canal (UK) is explored as an alternative means of monitoring pollution. Comparison of sediment-related analytical data by correlation analyses between each magnetic parameter and individual particle size classes (i.e. sand, silt and clay), and more discrete intervals within classes (e.g. fine sand or medium silt) are reported. XLF, XARM and SIRM parameters reveal few significant (p < .05; n = 60), weak (rs = .443), associations with clay content. Specific areas of historic anthropogenic activity are investigated and reveal improved correlations with )XLF vs. clay (r = .739, p < .001; n = 60), silt (r = -.612, p < .001; n = 60), and discrete fractions of sediment (r = .700-.868; p < .001). Comparison of mineral magnetic concentration and geochemistry are also reported with moderate to strong relationships between XLF, XARM, Fe, Pb and Co. Contrary to earlier research findings, the results for the Birmingham Canal Navigations Main Line indicate that magnetic measurements cannot always provide a predictable particle size proxy and it is only certain environments and/or specific settings that are appropriate for granulometric normalization by this technique.

L1-mediated axon outgrowth occurs via a homophilic binding mechanism.

The molecular mechanism by which the L1 cell adhesion molecule mediates neurite outgrowth has been examined. Purified L1 from mouse and L1 from chick brain were attached to nitrocellulose dishes. Both chick and mouse neurons were able to adhere to purified mouse L1 and chick L1. Both molecules promoted neurite extension from chick and mouse neurons. Addition of Fabs specific for chick L1 to the cultures inhibited chick neurite outgrowth on both mouse L1 and chick L1. These findings suggest that L1-like molecules support neurite outgrowth via a "homophilic" binding mechanism.

Patterns of usage and preferences of users for tuberculosis-related text messages and voice calls in Uganda.

BACKGROUND: Little information exists about mobile phone usage or preferences for tuberculosis (TB) related health communications in Uganda. METHODS: We surveyed household contacts of TB patients in urban Kampala, Uganda, and clinic patients in rural central Uganda. Questions addressed mobile phone access, usage, and preferences for TB-related communications. We collected qualitative data about messaging preferences. RESULTS: We enrolled 145 contacts and 203 clinic attendees. Most contacts (58%) and clinic attendees (75%) owned a mobile phone, while 42% of contacts and 10% of clinic attendees shared one; 94% of contacts and clinic attendees knew how to receive a short messaging service (SMS) message, but only 59% of contacts aged 45 years (vs. 96% of contacts aged <45 years, P = 0.0001) did so. All contacts and 99% of clinic attendees were willing and capable of receiving personal-health communications by SMS. Among contacts, 55% preferred detailed messages disclosing test results, while 45% preferred simple messages requesting a clinic visit to disclose results. CONCLUSIONS: Most urban household TB contacts and rural clinic attendees reported having access to a mobile phone and willingness to receive TB-related personal-health communications by voice call or SMS. However, frequent phone sharing and variable messaging abilities and preferences suggest a need to tailor the design and monitoring of mHealth interventions to target recipients.

Bub1p kinase activates the Saccharomyces cerevisiae spindle assembly checkpoint.

Saccharomyces cerevisiae BUB1 encodes a protein kinase required for spindle assembly checkpoint function. In the presence of spindle damage, BUB1 is required to prevent cell cycle progression into anaphase. We have identified a dominantly acting BUB1 allele that appears to activate the spindle assembly checkpoint pathway in cells with undamaged spindles. High-level expression of BUB1-5 did not cause detectable spindle damage, yet it delayed yeast cells in mitosis at a stage following bipolar spindle assembly but prior to anaphase spindle elongation. Delayed cells possessed a G2 DNA content and elevated Clb2p mitotic cyclin levels. Unlike cells delayed in mitosis by spindle damage or MPS1 kinase overexpression, hyperphosphorylated forms of the Mad1p checkpoint protein did not accumulate. Similar to cells overexpressing MPS1, the BUB1-5 delay was dependent upon the functions of the other checkpoint genes, including BUB2 and BUB3 and MAD1, MAD2, and MAD3. We found that the mitotic delay caused by BUB1-5 or MPS1 overexpression was interdependent upon the function of the other. This suggests that the Bub1p and Mps1p kinases act together at an early step in generating the spindle damage signal.

The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase.

Normal cell multiplication requires that the events of mitosis occur in a carefully ordered fashion. Cells employ checkpoints to prevent cycle progression until some prerequisite step has been completed. To explore the mechanisms of checkpoint enforcement, we previously screened for mutants of Saccharomyces cerevisiae which are unable to recover from a transient treatment with a benzimidazole-related microtubule inhibitor because they fail to inhibit subsequent cell cycle steps. Two of the identified genes, BUB2 and BUB3, have been cloned and described (M. A. Hoyt, L. Totis, and B. T. Roberts, Cell 66:507-517, 1991). Here we present the characterization of the BUB1 gene and its product. Genetic evidence was obtained suggesting that Bub1 and Bub3 are mutually dependent for function, and immunoprecipitation experiments demonstrated a physical association between the two. Sequence analysis of BUB1 revealed a domain with similarity to protein kinases. In vitro experiments confirmed that Bub1 possesses kinase activity; Bub1 was able to autophosphorylate and to catalyze phosphorylation of Bub3. In addition, overproduced Bub1 was found to localize to the cell nucleus.

Feasibility of a streamlined tuberculosis diagnosis and treatment initiation strategy.

OBJECTIVE: To assess the feasibility of a streamlined strategy for improving tuberculosis (TB) diagnostic evaluation and treatment initiation among patients with presumed TB. DESIGN: Single-arm interventional pilot study at five primary care health centers of a streamlined, SIngle-saMPLE (SIMPLE) TB diagnostic evaluation strategy: 1) examination of two smear results from a single spot sputum specimen using light-emitting diode fluorescence microscopy, and 2) daily transportation of smear-negative sputum samples to Xpert® MTB/RIF testing sites. RESULTS: Of 1212 adults who underwent sputum testing for TB, 99.6% had two smears examined from the spot sputum specimen. Sputum was transported for Xpert testing within 1 clinic day for 83% (907/1091) of the smear-negative patients. Of 157 (13%) patients with bacteriologically positive TB, 116 (74%) were identified using sputum smear microscopy and 41 (26%) using Xpert testing of smear-negative samples. Anti-tuberculosis treatment was initiated in 142 (90%) patients with bacteriologically positive TB, with a median time to treatment of 1 day for smear-positive patients and 6 days for smear-negative, Xpert-positive patients. CONCLUSION: The SIMPLE TB strategy led to successful incorporation of Xpert testing and rapid treatment initiation in the majority of patients with bacteriologically confirmed TB in a resource-limited setting.

Prenatal ethanol exposure decreases hippocampal 3H-vinylidene kainic acid binding in 45-day-old rats.

The effect of prenatal ethanol exposure on the kainate-sensitive subtype of glutamate receptor binding sites was studied using in vitro 3H-vinylidene kainic acid (VKA) autoradiography. Pregnant Sprague-Dawley rats were fed a liquid diet containing either 3.35% or 6.7% ethanol throughout gestation. Pair-fed dams received isocalorically matched liquid diets and a lab chow ad lib group served as control for paired feeding. At 45 days of age, the offspring were sacrificed and their brains analyzed for specific 3H-VKA binding. Compared to pair-fed controls, specific 3H-VKA binding was reduced by 13% to 32% in dorsal and ventral hippocampal CA3 stratum lucidum, entorhinal cortex and cerebellum of 45-day-old rats whose mothers consumed either 3.35% or 6.7% ethanol diets. The binding site reductions were statistically significant only in the ventral hippocampal formation and entorhinal cortex of the 3.35% ethanol diet group rats. Saturation of binding studies in the ventral hippocampal formation of 3.35% ethanol rats indicated that the decrease in specific 3H-VKA binding was due to a decrease in the total number of binding sites. Given the excitatory effect of kainic acid on the spontaneous firing rate of hippocampal CA3 pyramidal neurons, the reduction of kainate-sensitive glutamate binding in this region is consistent with the electrophysiological observation of decreased spontaneous activity of CA3 pyramidal neurons in fetal alcohol rats.

Prenatal exposure to ethanol decreases physiological plasticity in the hippocampus of the adult rat.

Prenatal exposure to ethanol has been associated with birth defects ranging in severity from physical dysmorphias and profound mental retardation to more subtle compromises of cognitive and behavioral function. Recent evidence has shown the hippocampus to be damaged both morphologically and neurochemically after such exposure in experimental animals. The functional implications of these changes have just recently begun to be addressed. We now report that long-term potentiation and potassium-induced excitability are decreased in hippocampal slices from adult animals exposed to ethanol in-utero. These deficits reflect a decrease in the plasticity of the hippocampal formation. This alteration may be one factor contributing to the memory and learning deficits associated with in-utero exposure to ethanol.

Prenatal ethanol exposure decreases hippocampal 3H-glutamate binding in 45-day-old rats.

The effect of prenatal ethanol exposure on putative glutamate receptor binding sites in rat brain was studied using radiohistochemical techniques. Pregnant Sprague-Dawley rats were fed a liquid diet containing either 3% or 6% (vol./vol.) ethanol throughout gestation. Pair-fed dams received isocalorically matched liquid diets and a lab chow ad lib group served as control for paired feeding. At 45 days of age, the offspring were sacrificed and their brains analyzed by in vitro 3H-glutamate autoradiography. Compared to pair-fed controls, specific 3H-glutamate binding was reduced by 49-53% in regions of the dorsal hippocampal formation of 45-day-old rats whose mothers consumed either 3% or 6% ethanol diets. Specific 3H-glutamate binding was decreased also in the ventral hippocampal formation, entorhinal and posterior neocortex, but to a less consistent degree and magnitude than in dorsal hippocampal formation of fetal alcohol rats. The reduction in hippocampal 3H-glutamate binding 45 days after prenatal ethanol exposure suggests a long-lasting net decrease in glutamate-mediated excitatory neurotransmission within the hippocampal formation of fetal alcohol rats. This glutamate receptor binding site alteration may be one factor contributing to a decrease in long-term potentiation of hippocampal CA1 pyramidal neurons in fetal alcohol rats. In addition, this alteration may underlie learning and other behavioral deficits associated with functional defects of the hippocampal formation.

Dog owners' perceptions of breed-specific dangerous dog legislation in the UK.

The aim of this study was to identify both the level and source of knowledge that dog owners in the UK have of the Dangerous Dogs Act 1991. In order to acquire such information a questionnaire was designed and distributed using two main methods over a period of five months. Questionnaires were distributed via three pet-related online forums and by hand at two locations within five predefined areas in England. In total, 459 responses were received. Of these, 21.4 per cent were unable to name a single type of banned dog and 81.9 per cent of respondents agreed that information on dog legislation was not publicised enough. The knowledge of banned breeds among the dog owners surveyed was low and respondents expressed a desire to see the law relating to dangerous dogs in the UK either changed or improved.

The metaphase to anaphase transition: a case of productive destruction.

The metaphase to anaphase transition is a point of no return; the duplicated sister chromatids segregate to the future daughter cells, and any mistake in this process may be deleterious to both progeny. At the heart of this process lies the anaphase inhibitor, which must be degraded in order for this transition to take place. The degradation of the anaphase inhibitor occurs via the ubiquitin-degradation pathway, and it involves the activity of the cyclosome/anaphase promoting complex (APC). The fidelity of the metaphase to anaphase transition is ensured by several different regulatory mechanisms that modulate the activity of the cyclosome/APC. Great advancements have been made in this field in the past few years, but many questions still remain to be answered.

Lens design for a white-light cosine-transform achromat.

We describe the lens design for a twin-imaging white-light interferometer in which the interference pattern at the exit-pupil plane is the cosine transform of the spatial-intensity distribution of the object. The achromatic condition in terms of optical power is derived. The analysis of the transform aberration shows that the even aberrations, e.g., spherical aberration and field curvature, do not degrade the cosine transform and need not be corrected. This significant simplification permits us to design systems with good performance and uncomplicated lens structures. We present a lens design with three elements and a length of 320 mm. The system is capable of resolving more than 10(6) pixels with an operating spectral bandwidth of 100 nm. The results of an experiment with an early four-element design are also presented.

Effects of ethanol on rat hypothalamic luteinizing hormone releasing hormone. A study utilizing radioimmunoassay.

To further understand the mechanism of action by which ethanol (ETOH) decreases plasma luteinizing hormone (LH) levels, the effects of multiple i.p. injections of EOH (1.0--1.5 g/kg) or saline on hypothalamic luteinizing hormone releasing hormone (LHRH) and plasma LH concentrations were evaluated in intact and castrate male rats. After injections, animals were decapitated, brains rapidly removed, and blocks containing the hypothalamus [with median eminence (ME)] were isolated. Hypothalami were subjected to acetic acid extraction and LHRH content quantitated via radioimmunoassay (RIA). Hypothalamic LHRH was found to be inversely correlated with plasma LH. In response to castration, both saline and ETOH-treated rats showed a decrease in hypothalamic LHRH content with a concomitant increase in plasma LH; however, the ETOH-treated animals retained significantly greater concentrations of LHRH and showed significantly lower plasma LH levels when compared to saline-treated controls. Likewise, ETOH-treated intact animals showed significant increases in LHRH content, with LH levels remaining significantly lower than the saline-treated intact controls. Thus, these data from both intact and castrate rats provide evidence to support the hypothesis that alcohol-induced decreases in LH levels are due to a diminished release rate of hypothalamic LHRH.

Fertility impairment in granulocyte-macrophage colony-stimulating factor-deficient mice.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been identified as a potentially important mediator of intercellular communication in the female reproductive tract, with principal target cells being the large populations of myeloid leukocytes in the cycling and pregnant uterus, the preimplantation embryo, and trophoblast cells of the developing placenta. To determine the physiological significance of this cytokine in reproduction, the fertility of genetically GM-CSF-deficient (GM-/-) mice was examined. Implantation rates were normal in GM-/- mice, and viable pups were produced. However, the mean litter sizes of GM-/- x GM-/- breeding pairs were 25% smaller at weaning than those of GM+/- x GM+/- pairs, due to fetal death late in gestation and early in postnatal life, with a disproportionate loss of male pups. On Day 17 of pregnancy, the mean number of resorbing and malformed fetuses was twice as high in pregnant GM-/- females (21%, vs. 11% in GM+/- females); the mean fetal weight and the mean fetal:placental ratio in surviving conceptuses were diminished by 7% and 6%, respectively; and the number of very small fetuses (< 500 mg) was 9-times as high (23% vs. 2.5%). Mortality during the first 3 wk of life was 4.5-times as high in pups born to GM-/- mothers (9%, vs. 2% in GM+/- females), and diminished size persisted in GM-/- pups, particularly males, into adulthood. The detrimental effect of maternal GM-CSF deficiency was less apparent when GM-/- females were mated with GM+/+ males; litter sizes at birth and at weaning were not significantly smaller than in GM+/- matings, and fetal weights and fetal:placental ratios were also comparable. When polymerase chain reaction was used to genotype embryonic tissue in heterozygote matings, GM-/- fetuses from GM-/- females were found to be smaller than their GM+/- littermates and smaller than GM-/- fetuses gestated in GM+/- females. The size and distribution of uterine granulocyte and macrophage populations were normal during the estrous cycle, during early pregnancy, and in midgestation. Analysis of placental structure revealed that the ratio of labyrinthine to spongiotrophoblast areas was reduced by approximately 28% in GM-/- placentae, and the proportion of vacuolated trophoblast "glycogen cells" in the spongiotrophoblast layer was diminished. Compromised placental function as a result of subtle developmental aberrations may therefore partially account for embryonic growth retardation in GM-CSF-deficient mice. Collectively, these studies show that fetal growth and viability are jeopardized in the absence of maternal GM-CSF. The detrimental effects are most clearly evident when the conceptus is also GM-CSF deficient, suggesting that GM-CSF of either maternal or fetal origin is required for optimal growth and survival of the fetus in mice.