C60 chain phases on ZnPc/Ag(111) surfaces: Supramolecular organization driven by competing interactions.

Serpentine chain C60 phases were observed in scanning tunneling microscopy (STM) images of C60 layers on zinc phthalocyanine (ZnPc) or pentacene covered Ag(111) and Au(111) surfaces. This low-density, quasi-one-dimensional organization contrasts starkly with the close-packed hexagonal phases observed for C60 layers on bare metal substrates. STM was employed to perform a detailed investigation of these chain structures for C60/ZnPc/Ag(111) heterolayers. Motivated by the similarity of these chain phases, and the chain and stripe organization occurring in dipole-fluid systems, we investigated a model based on competing van der Waals attractions and electrostatic repulsions between C60 molecules as an explanation for the driving force behind these monolayer phases. Density functional theory (DFT) calculations revealed significant charge transfer to C60 from the Ag(111) substrate, through the intervening ZnPc layer, inducing electrostatic interactions between C60 molecules. Molecular dynamics simulations performed with attractive van der Waals interactions plus repulsive dipole-dipole interactions reproduced the C60 chain phases with dipole magnitudes consistent with DFT calculations.

Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound.

BACKGROUND: In patients with breast cancer, grey-scale ultrasound often fails to identify lymph node (LN) metastases. We aimed to validate the technique of contrast-enhanced ultrasound (CEUS) as a test to identify sentinel lymph node (SLN) metastases and reduce the numbers of patients requiring a completion axillary node clearance (ANC). METHODS: 371 patients with breast cancer and a normal axillary ultrasound were recruited. Patients received periareolar intra-dermal injection of microbubble contrast agent. Breast lymphatics were visualised by CEUS and followed to identify and biopsy axillary SLN. Patients then underwent standard tumour excision and either SLN excision (benign biopsy) or axillary clearance (malignant biopsy) with subsequent histopathological analysis. RESULTS: The technique failed in 46 patients, 6 patients had indeterminate biopsy results and 24 patients were excluded. In 295 patients with a conclusive SLN biopsy, the sensitivity of the technique was 61% and specificity 100%. Given a benign SLN biopsy result, the post-test probability that a patient had SLN metastases was 8%. 35 patients were found to have SLN metastases and had a primary ANC (29 macrometastases and 6 micrometastases/ITC). There were 22 false negative results (10 macrometastases and 12 micrometastases). Macrometastases in core biopsy specimens correlated with LN macrometastases on surgical excision. CONCLUSION: Pre-operative biopsy of SLN reduced the numbers of patients requiring completion ANC. Despite the low sensitivity, only 22 patients (8%) with a benign SLN biopsy were subsequently found to have LN metastases. Without the confirmation of macrometastases on core biopsy specimens, patients with micrometastases/ITC may be inadvertently selected for primary ANC.

Assessment of the environmental fate and ecotoxicity of N,N-diethyl-m-toluamide (DEET).

N,N-diethyl-m-toluamide (DEET) is a key active ingredient in many insect repellents available commercially throughout the world. Owing to its popularity among consumers for nearly 30 years, considerable work conducted in the past has demonstrated-and continues to demonstrate-that human exposure to DEET poses no significant health risk to the general population. The results of several studies reported in this paper describe more recent work to understand the environmental fate of DEET, particularly in surface waters and soil, and the potential hazards to aquatic and terrestrial organisms. In summary, DEET enters the environment through several pathways: directly into air during spray application; to surface water from overspray and indirectly via wastewater treatment plant (WTTP) discharges (as a result of washing of skin and laundering of clothing); or to soil via overspray and application of treated sewage as an amendment. Multimedia environmental fate modeling predicts that DEET entering the environment is retained either in receiving waters (∼79%) or in soil (∼21%). Based on its physicochemical properties, DEET is expected to be moderately mobile in the soil column. In surface waters and soil, DEET degrades at a moderate to rapid rate (its half-life is measured in days to weeks). The small amounts of DEET retained in air are subject to rapid photo-oxidation via hydroxyl radical-mediated degradation or, if in droplet form, gravitational settling to soil or water. DEET does not interfere with ozone formation in the upper atmosphere. The bioaccumulation potential of DEET is low; it is neither a persistent, bioaccumulative toxicant nor a persistent organic pollutant. Among aquatic species, acute effect concentrations range between 4 and 388 mg/L. The chronic no-observed effect concentrations (NOEC) for daphnids and green algae range from approximately 0.5 to 24 mg/L. Measured concentrations of DEET in surface waters are several hundreds to thousands of times lower than the lowest NOEC measured, and thus the probability for adverse effects to environmental species is low. A separate paper by Aronson et al. (this issue) supports this conclusion by quantitatively exploring the risks to the aquatic environment using a combination of monitoring data and exposure modeling.

The impact of obesity on receipt of adjuvant chemotherapy for breast cancer in the National Comprehensive Cancer Network (NCCN) centers.

Disparities in the receipt of adjuvant chemotherapy for early stage breast cancer is an important factor influencing mortality. We investigated whether greater body mass index (BMI) decreases receipt of adjuvant chemotherapy among women with operable breast cancer. In the NCCN breast cancer outcomes database, we identified women aged ≤ 70 with newly diagnosed stage I, II, or III breast cancer between 1997 and 2007, for whom use of adjuvant chemotherapy was classified as either standard-of-care or discretionary based on their clinical characteristics. Body mass index was assessed in categories (<18.5 kg/m(2) [underweight], 18.5 to <25 kg/m(2) [normal], 25 to <30 kg/m(2) [overweight], 30-39 kg/m(2) [obese], ≥ 40 kg/m(2) [extreme obese]). Multivariable logistic regression analysis was used to examine the association between BMI and receipt of chemotherapy in each classification group. 9,527 women were eligible for the study; 40% normal weight or less; 31% overweight; 24% obese; and 5% extremely obese. In multivariable analysis, there was no significant association between BMI and receipt of chemotherapy in either classification group. Among women for whom chemotherapy would be considered standard-of-care, older age (P < 0.001), comorbidity (P < 0.001), and non-Hispanic black ethnicity (P = 0.002) were associated with a lower likelihood of receipt of chemotherapy; however, the effect of ethnicity was not modified by obesity. Among women treated for operable breast cancer in the NCCN centers, BMI had no impact on receipt of adjuvant chemotherapy and did not modify the lower likelihood of chemotherapy among non-Hispanic black patients. Further investigation is needed into other factors that contribute to patient disparities in the receipt of chemotherapy in major academic centers.

Preoperative localization of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasonography in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy is the standard procedure for axillary staging in early breast cancer. Lymphatic imaging after intraparenchymal microbubble injection has been reported in animal models. The aim of this study was to identify and localize SLNs before surgery by contrast-enhanced ultrasonography after intradermal injection of microbubbles in patients with breast cancer. METHODS: Fifty-four consecutive, consenting patients with primary breast cancer were recruited. Patients received a periareolar intradermal injection of microbubble contrast agent. Breast lymphatics were visualized by ultrasonography and followed to identify putative axillary SLNs. A guidewire was deployed to localize the SLN. The next day, patients underwent standard tumour excision and SLN biopsy. RESULTS: SLNs were identified and guidewires inserted in 48 patients. In these patients operative findings confirmed that the wired lymph nodes were SLNs. The sensitivity of SLN detection, compared with radioisotope and blue dye, was 89 per cent. Five patients were found to have metastases in SLNs. In these patients the SLNs were identified correctly and localized before surgery with guidewires. CONCLUSION: SLNs may be identified and localized before surgery using contrast-enhanced ultrasonography after injection of microbubbles.

Incidence, pathology and outcome of gynaecological cancer in patients under the age of 21 years in South-west England 1995-2004: comparison of data from regional, national and international registries.

We analysed the incidence, tumour types, management and outcome of gynaecological cancer diagnosed from 1995-2004 in females <21 years in south-west England. Data from the South West Cancer Intelligence Service were compared with those from regional and national registries. A total of 63 patients had gynaecological malignancies: 49 ovarian; nine cervical; the remainder vaginal, uterine or pelvic. The median age was 16 years. Germ cell tumours (26) and carcinomas (6) were the commonest primary ovarian and cervical tumours respectively. Most patients had fertility-sparing procedures. Only seven required re-operation. Information about chemoradiotherapy was incomplete. Four deaths occurred. All patients were followed >3 years and 68% >5 years, with 94% survival to date. Fertility preservation did not impair survival. Mortality is an inadequate indicator of outcome; cancer registries should record information on fertility and pregnancy outcomes, second tumours and long-term treatment-related complications. Improved management requires greater centralised assessment of histology, follow-up and adjuvant treatment.

Direct-to-consumer advertising for bleeding disorders: a content analysis and expert evaluation of advertising claims.

OBJECTIVE: In the United States, the Food and Drug Administration (FDA) requires that all direct-to-consumer advertising (DTCA) contain both an accurate statement of a medication's effects ('truth') and an even-handed discussion of its benefits and risks/adverse effects ('fair balance'). DTCA for medications to treat rare diseases such as bleeding disorders is unlikely to be given high priority for FDA review. METHODS: We reviewed all DTCA for bleeding disorder products appearing in the patient-directed magazine HemeAware from January 2004 to June 2006. We categorized the information presented in each advertisement as benefit, risk/adverse effect, or neither, and assessed the amount of text and type size devoted to each. We also assessed the readability of each type of text using the Flesch Reading Ease Score (FRES, where a score of >or=65 is considered of average readability), and assessed the accuracy of the advertising claims utilizing a panel of five bleeding disorder experts. RESULTS: A total of 39 unique advertisements for 12 products were found. On average, approximately twice the amount of text was devoted to benefits as compared with risks/adverse effects, and the latter was more difficult to read [FRES of 32.0 for benefits vs. 20.5 for risks/adverse effects, a difference of 11.5 (95% CI: 4.5-18.5)]. Only about two-thirds of the advertising claims were considered by a majority of the experts to be based on at least low-quality evidence. CONCLUSION: As measured by our methods, print DTCA for bleeding disorders may not reach the FDA's standards of truth and fair balance.

Cytokinin vectors mediate marker-free and backbone-free plant transformation.

Conventional Agrobacterium-mediated transformation methods rely on complex and genotype-specific tissue culture media for selection, proliferation, and regeneration of genetically modified cells. Resulting transgenic plants may not only contain selectable marker genes but also carry fragments of the vector backbone. Here, we describe a new method for the production of transgenic plants that lack such foreign DNA. This method employs vectors containing the bacterial isopentenyltransferase (ipt) gene as backbone integration marker. Agrobacterium strains carrying the resulting ipt gene-containing "cytokinin" vectors were used to infect explants of various Solanaceous plant species as well as canola (Brassica napus). Upon transfer to hormone-free media, 1.8% to 9.9% of the infected explants produced shoots that contained a marker-free T-DNA while lacking the backbone integration marker. These frequencies often equal or exceed those for backbone-free conventional transformation.

Development of an in planta method for transformation of alfalfa (Medicago sativa).

Conventional methods in transforming alfalfa (Medicago sativa) require multiple tissue culture manipulations that are time-consuming and expensive, while applicable only to a few highly regenerable genotypes. Here, we describe a simple in planta method that makes it possible to transform a commercial variety without employing selectable marker genes. Basically, young seedlings are cut at the apical node, cold-treated, and vigorously vortexed in an Agrobacterium suspension also containing sand. About 7% of treated seedlings produced progenies segregating for the T-DNA. The vortex-mediated seedling transformation method was applied to transform alfalfa with an all-native transfer DNA comprising a silencing construct for the caffeic acid o-methyltransferase (Comt) gene. Resulting intragenic plants accumulated reduced levels of the indigestible fiber component lignin that lowers forage quality. The absence of both selectable marker genes and other foreign genetic elements may expedite the governmental approval process for quality-enhanced alfalfa.

Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. METHODS: This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at

Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth. METHODS: This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at

The impact of improving outcomes guidance on surgical management of vulval squamous cell cancer in southwest England (1997-2002).

OBJECTIVE: The objective of this study was to assess the impact of reorganisation of gynaecological services in southwest England following adoption of regionally agreed evidence-based guidelines and publication of the National Improving Outcomes Guidance in 1999. DESIGN: Prospective audit with cross-checking against histological reports. SETTING: All 19 acute hospitals in the four Cancer Networks of southwest England. SAMPLE: All subjects with squamous or verrucous vulval cancer diagnosed between 1997 and 2002. METHOD: A one-page minimum data set proforma agreed by the South West Gynaecology Tumour Panel was completed by surgeons after treatment of each patient, and was sent to South West Cancer Intelligence Service for entry, collation and analysis. Data are presented for the years 1997 to 2002 inclusive, and comparisons were made between each of the three 2-year cohorts. MAIN OUTCOME MEASURES: These are standards derived from the guidance. RESULTS: There were 436 squamous or verrucous vulval cancers registered. Recording of staging was missing in 20% of subjects. The percentage of subjects operated upon by lead gynaecological cancer surgeons increased from 78% in cohort 1 to 93% in cohort 3 (P < 0.001). There is a trend towards more conservative operations, which have lower co-morbidity. High activity surgeons achieved better rates of tumour-free skin margins, but even these were adequate only in 49% of operations. Lymphadenectomy rates did not follow guidance. CONCLUSION: Centralisation of care of this rare cancer should continue, but specialists need to increase their efforts to ensure adequate skin margins and lymphadenectomy rates while balancing morbidity and the likelihood of recurrence in both fit and frail patients.

Object-based classification of residential land use within Accra, Ghana based on QuickBird satellite data.

A segmentation and hierarchical classification approach applied to QuickBird multispectral satellite data was implemented, with the goal of delineating residential land use polygons and identifying low and high socio-economic status of neighbourhoods within Accra, Ghana. Two types of object-based classification strategies were tested, one based on spatial frequency characteristics of multispectral data, and the other based on proportions of Vegetation-Impervious-Soil sub-objects. Both approaches yielded residential land-use maps with similar overall percentage accuracy (75%) and kappa index of agreement (0.62) values, based on test objects from visual interpretation of QuickBird panchromatic imagery.

Diffuse CNS vasculopathy with chronic Epstein-Barr virus infection in X-linked lymphoproliferative disease.

We report a patient with X-linked lymphoproliferative disease (XLP) who developed multiple central nervous system (CNS) manifestations of Epstein-Barr virus infection. XLP, or Duncan syndrome, is a rare inherited disorder characterized by the inability to clear Epstein-Barr virus infection. In addition to Epstein-Barr virus encephalitis, CNS lymphoproliferative disease, and lymphoma, this patient also developed MR angiographic evidence of diffuse fusiform aneurysmal dilation of intracranial vessels.

Stage III and IV ovarian cancer in the South West of England: five-year outcome analysis for cases treated in 1998.

This study evaluates the 5-year outcome data for the management of advanced ovarian cancer in the South West of England. Anonymized data for 361 stage III and IV ovarian cancers registered between January 1, 1998, and December 31, 1998, were obtained from the central gynecological tumor database. The following data were identified: age at diagnosis, FIGO stage, American Society of Anesthesiologists (ASA) grade, tumor differentiation, treating network and surgeon, amount of residual disease after debulking surgery, current life status, and date of death if applicable. Survival analysis was performed using Kaplan-Meier crude survival for univariate analysis, and multivariate analysis was performed by Cox regression. In our data the 5-year survival for patients with stage III was 16% and with stage IV was 10%. Survival analysis demonstrated that patients in whom the disease was debulked to less than 1 cm were more likely to be alive 5 years after diagnosis than those with a 2-cm residuum (P < 0.0001). There was no significant survival difference for those patients operated on by subspecialist surgeons despite these surgeons being twice as likely to achieve optimal debulking. Therefore, there must be other variables influencing survival apart from cytoreductive surgery. While there is near-complete data collection about ovarian cancer surgery, our database on chemotherapy is incomplete. This is clearly crucial for a complete view of cancer care in our region.

Impacts of mercury contaminated mining waste on soil quality, crops, bivalves, and fish in the Naboc River area, Mindanao, Philippines.

Rice paddy fields in the Naboc area, near Monkayo on the island of Mindanao, Philippines, have been irrigated four times a year over the last decade using Naboc River water contaminated with mercury (Hg) by artisanal gold mining in the Diwalwal area. Silt containing up to at least 90 mg Hg/kg (d.w.) has been deposited in rice paddy fields during the 1990s and this has been repeatedly mixed into the rice root zone through ploughing. Hg in the rice paddy field soils averages 24 mg Hg/kg and generally exceeds the UK and Canadian soil quality thresholds for agricultural soils as well as the proposed Dutch Intervention value and the USEPA soil ingestion Soil Screening Level (SSL) for inorganic Hg. Much lower Hg concentrations (0.05-0.99 mg/kg) within the range expected for uncontaminated soils, characterise soils on which corn and bananas are cultivated, largely because these are not irrigated with Hg-contaminated water from the Naboc River. The estimated total weekly MeHg intake for a person living in the Naboc area related to the weekly consumption of 2.1 kg of rice grown on Hg-contaminated soils (15 microg MeHg) in conjunction with 1 kg of fish (220 microg MeHg) and 100 g of mussels (50 microg MeHg) from the Naboc River, would total 285 microg MeHg (equivalent to 4.75 microg/kg bw for a 60 kg adult), which is nearly three times the JECFA PTWI of 1.6 microg/kg bw. This will significantly contribute to the population mercury exposure and might explain why 38% of the local inhabitants were classified as Hg intoxicated during a mercury toxicity assessment [Drasch GS, Böse, O'Reilly S, Beinhoff C, Roider G, Maydl S. The Mt. Diwata study on the Philippines 1999-assessing mercury intoxication of the population by small scale gold mining. Sci Total Environ 2001; 267(1-3): 151-168.].

Pause point spectra in DNA constant-force unzipping.

Under constant applied force, the separation of double-stranded DNA into two single strands is known to proceed through a series of pauses and jumps. Given experimental traces of constant-force unzipping, we present a method whereby the locations of pause points can be extracted in the form of a pause point spectrum. A simple theoretical model of DNA constant-force unzipping is presented, which generates theoretical pause point spectra through Monte Carlo simulation of the unzipping process. The locations of peaks in the experimental and theoretical pause point spectra are found to be nearly coincident below 6000 basepairs for unzipping the bacteriophage lambda-genome. The model only requires the sequence, temperature, and a set of empirical basepair binding and stacking energy parameters, and the good agreement with experiment suggests that pause point locations are primarily determined by the DNA sequence. The model is also used to predict pause point spectra for the bacteriophage phi X174 genome. The algorithm for extracting the pause point spectrum might also be useful for studying related systems which exhibit pausing behavior such as molecular motors.

Assessment of a 2,4,6-trinitrotoluene-contaminated site using Aporrectodea rosea and Eisenia andrei in mesocosms.

Polynitro-organic compounds such as 2,4,6-trinitrotoluene (TNT) can be released into the environment from production and processing facilities and military firing ranges as well as through field use and disposal practices. Based on laboratory toxicity data, TNT has lethal (at >/=260 mg TNT/kg dry soil) and sublethal effects (at >/=59 mg TNT/kg dry soil) to the earthworm. However, field studies are needed to relate exposure of organisms to explosives in mixed-contaminated soil under field conditions and to define effects-based ecotoxicologic benchmarks for TNT-contaminated soil. In the present study, the lethal and sublethal effects of a 10-day in situ exposure at a TNT-contaminated field site using mesh-bag mesocosms were assessed. In addition to the survival end point, the biomarkers of earthworm exposure and effect-including tissue residues, lysosomal neutral red retention time (NRRT), and total immune activity (TIA)-were measured. Concentrations of TNT in soil mesocosms ranged from 25 to 17,063 mg/kg. Experiments indicated a trend toward decreasing survival of caged Aporrectodea rosea and Eisenia andrei as the concentration of TNT and total nitroaromatic compounds increased. E. andrei tolerated higher concentrations of TNT (up to 4050 mg/kg dry soil) in mesocosms than did indigenous earthworms, who survived only at

High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients.

The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 microM for cGMP and 2.4 microM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialis, Lilly-ICOS), vardenafil (Levitra, Bayer-GSK), and sildenafil (Viagra, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.