An investigation of the effects from a urethral warming system on temperature distributions during cryoablation treatment of the prostate: a phantom study.

Introduction of urethral warmers to aid cryosurgery in the prostate has significantly reduced the incidence of urethral sloughing; however, the incidence rate still remains as high as 15%. Furthermore, urethral warmers have been associated with an increase of cancer recurrence rates. Here, we report results from our phantom-based investigation to determine the impact of a urethral warmer on temperature distributions around cryoneedles during cryosurgery. Cryoablation treatments were simulated in a tissue mimicking phantom containing a urethral warming catheter. Four different configurations of cryoneedles relative to urethral warming catheter were investigated. For each configuration, the freeze-thaw cycles were repeated with and without the urethral warming system activated. Temperature histories were recorded at various pre-arranged positions relative to the cryoneedles and urethral warming catheter. In all configurations, the urethral warming system was effective at maintaining sub-lethal temperatures at the simulated surface of the urethra. The warmer action, however, was additionally demonstrated to potentially negatively impact treatment lethality in the target zone by elevating minimal temperatures to sub-lethal levels. In all needle configurations, rates of freezing and thawing were not significantly affected by the use of the urethral warmer. The results indicate that the urethral warming system can protect urethral tissue during cryoablation therapy with cryoneedles placed as close as 5mm to the surface of the urethra. Using a urethral warming system and placing multiple cryoneedles within 1cm of each other delivers lethal cooling at least 5mm from the urethral surface while sparing urethral tissue.

Seatbelt usage: is there an association with obesity?

Wearing a seatbelt can prevent motor vehicle crash deaths. While primary seatbelt laws are designed to encourage vehicle passengers to wear seatbelts by allowing law enforcement officers to issue tickets when passengers do not wear seatbelts, discomfort may discourage obese individuals from wearing a seatbelt. The objective of this study is to assess the association between state-level obesity and seatbelt usage rates in the US, and to examine the possible role played by seatbelt laws in these associations. The strength of the association between obesity rates, seatbelt usage, and primary seatbelt laws at the state level is investigated using data from 2006 to 2011. Linear regression analysis is employed. This model estimates that increasing the obesity rate by 1% in a state where a primary seatbelt law (by which law enforcement officers can issue a ticket when seatbelts are not worn) is in effect is associated with a 0.06% decrease in seatbelt usage. However the same percentage of increase in the obesity rate in a state where no primary seatbelt law is in effect is associated with a 0.55% decrease in seatbelt usage. The magnitude of the statistical association between state obesity rates and state-level seatbelt usage is related to the existence of a primary seatbelt law, such that obesity has less impact on seatbelt usage in states where primary seatbelt laws are in effect.

Discharge-driven electric oxygen-iodine laser superlinear enhancement via increasing g0L.

The authors report the development of an electric oxygen-iodine laser with higher output using a larger product of gain and gain length, g0L. A factor of 4.4 increase in laser power output on the 1315 nm atomic iodine transition was achieved with a factor of 3 increase in gain length. I(2P1/2) is pumped using energy transferred from O2(a1Δ) produced by flowing a gas mixture of O2-He-NO through three coaxial geometry radio-frequency discharges. Continuous wave (CW) average total laser power of 481 W was extracted with g0L=0.042.

Linking optimization and ecological models in a decision support tool for oyster restoration and management.

Restoration of ecologically important marine species and habitats is restricted by funding constraints and hindered by lack of information about trade-offs among restoration goals and the effectiveness of alternative restoration strategies. Because ecosystems provide diverse human and ecological benefits, achieving one restoration benefit may take place at the expense of other benefits. This poses challenges when attempting to allocate limited resources to optimally achieve multiple benefits, and when defining measures of restoration success. We present a restoration decision-support tool that links ecosystem prediction and human use in a flexible "optimization" framework that clarifies important restoration trade-offs, makes location-specific recommendations, predicts benefits, and quantifies the associated costs (in the form of lost opportunities). The tool is illustrated by examining restoration options related to the eastern oyster, Crassostrea virginica, which supported an historically important fishery in Chesapeake Bay and provides a range of ecosystem services such as removing seston, enhancing water clarity, and creating benthic habitat. We use an optimization approach to identify the locations where oyster restoration efforts are most likely to maximize one or more benefits such as reduction in seston, increase in light penetration, spawning stock enhancement, and harvest, subject to funding constraints and other limitations. This proof-of-concept Oyster Restoration Optimization model (ORO) incorporates predictions from three-dimensional water quality (nutrients-phytoplankton zooplankton-detritus [NPZD] with oyster filtration) and larval transport models; calculates size- and salinity-dependent growth, mortality, and fecundity of oysters; and includes economic costs of restoration efforts. Model results indicate that restoration of oysters in different regions of the Chesapeake Bay would maximize different suites of benefits due to interactions between the physical characteristics of a system and nonlinear biological processes. For example, restoration locations that maximize harvest are not the same as those that would maximize spawning stock enhancement. Although preliminary, the ORO model demonstrates that our understanding of circulation patterns, single-species population dynamics and their interactions with the ecosystem can be integrated into one quantitative framework that optimizes spending allocations and provides explicit advice along with testable predictions. The ORO model has strengths and constraints as a tool to support restoration efforts and ecosystem approaches to fisheries management.

Photoemission studies of high-tc superconductors: the superconducting gap.

Over the last several years there have been great improvements in the energy resolution and detection efficiency of angle-resolved photoemission spectroscopy. These improvements have made it possible to discover a number of fascinating features in the electronic structure of the high transition temperature (T(c)) superconductors: apparently bandlike Fermi surfaces, flat-band saddle points, and nested Fermi surface sections. Recent work suggests that these features, previously thought explainable only by one-electron band theory, may be better understood with a many-body approach. Furthermore, other properties of the high-T(c) superconductors, which are difficult to understand with band theory, are well described using a many-body picture. Angle-resolved photoemission spectroscopy has also been used to investigate the nature of the superconducting pairing state, revealing an anisotropic gap consistent with a d-wave order parameter and fueling the current debate over s-wave versus d-wave superconductivity.

Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase.

Serial human immunodeficiency virus type-1 (HIV-1) isolates were obtained from five individuals with acquired immunodeficiency syndrome (AIDS) who changed therapy to 2',3'-dideoxyinosine (ddI) after at least 12 months of treatment with 3'-azido-3'-deoxythymidine (zidovudine, AZT). The in vitro sensitivity to ddI decreased during the 12 months following ddI initiation, whereas AZT sensitivity increased. Analysis of the reverse transcriptase coding region revealed a mutation associated with reduced sensitivity to ddI. When this mutation was present in the same genome as a mutation known to confer AZT resistance, the isolates showed increased sensitivity to AZT. Analysis of HIV-1 variants confirmed that the ddI resistance mutation alone conferred ddI and 2',3'-dideoxycytidine resistance, and suppressed the effect of the AZT resistance mutation. The use of combination therapy for HIV-1 disease may prevent drug-resistant isolates from emerging.

Effects of phosphatidylethanolamine and phosphatidylcholine in membrane phospholipid on binding of phorbol ester in rat mammary carcinoma cells.

Mammalian cells in culture can be classified as either ethanolamine (Etn)-responsive or Etn-nonresponsive with regard to their growth. Epithelial cells and some of their transformed derivatives are the Etn-responsive type. When these cells are grown without Etn, the content of membrane phospholipid becomes significantly altered. Namely, the content of phosphatidylethanolamine is reduced and that of phosphatidylcholine is increased. In addition, the growth rate of these cells is reduced. Therefore, it is likely that the phosphatidylethanolamine deficiency or phosphatidylcholine excess is unsuitable for some membrane-associated functions resulting in the cessation of growth. In order to test the above hypothesis, we examined the binding of a tumor-promoting phorbol ester, [3H]phorbol 12,13-dibutyrate (PDB), to an Etn-responsive rat mammary carcinoma cell line 64-24 grown with (Etn-plus) or without Etn (Etn-minus). The time course of binding was very similar between Etn-plus and -minus cells, except that the level of saturation was higher in Etn-plus cells, whereas the time course of chase of the bound PDB was significantly different between the two types of cells. Both types of cells have one class of binding sites for PDB. The dissociation constant (Kd) for [3H]PDB in Etn-plus cells was 34.0 nM and the number of binding sites at saturation was 2.7 x 10(12)/mg protein or 3.6 x 10(5)/cell. The corresponding values in Etn-minus cells were 61.4 nM and 3.2 x 10(12)/mg protein or 5.4 x 10(5)/cell, respectively. Although the difference in Kd values of the two types of cells was only 2-fold, this difference was statistically significant. On the other hand, the number of binding sites/mg protein in these cells was very similar. Since the amount of protein/cell was 1.4-fold higher in Etn-minus cells as compared to that of Etn-plus cells, the number of binding sites/cell was larger in Etn-minus cells. PDB affected the rate of proliferation of 64-24 cells differently, depending on whether they were grown in the presence or absence of Etn. These results suggest that the phosphatidylethanolamine and/or phosphatidylcholine content of the membrane phospholipid affects cellular functions mediated by phorbol esters.

Erratum: Atomic scale modelling of hexagonal structured metallic fission product alloys.

[This corrects the article DOI: 10.1098/rsos.140292.].

Atomic scale modelling of hexagonal structured metallic fission product alloys.

Noble metal particles in the Mo-Pd-Rh-Ru-Tc system have been simulated on the atomic scale using density functional theory techniques for the first time. The composition and behaviour of the epsilon phases are consistent with high-entropy alloys (or multi-principal component alloys)-making the epsilon phase the only hexagonally close packed high-entropy alloy currently described. Configurational entropy effects were considered to predict the stability of the alloys with increasing temperatures. The variation of Mo content was modelled to understand the change in alloy structure and behaviour with fuel burnup (Mo molar content decreases in these alloys as burnup increases). The predicted structures compare extremely well with experimentally ascertained values. Vacancy formation energies and the behaviour of extrinsic defects (including iodine and xenon) in the epsilon phase were also investigated to further understand the impact that the metallic precipitates have on fuel performance.

Dual expression of human leukocyte antigen molecules and the B7-1 costimulatory molecule (CD80) on human melanoma cells after particle-mediated gene transfer.

The aim of this study was to determine if human melanoma cells could be molecularly modified by particle-mediated gene transfer with a "gene gun", using genes for interferon-gamma (IFN-gamma), the B7-1 costimulatory molecule (CD80), and human leukocyte antigen (HLA)-A2, to augment expression of both HLA molecules and B7-1. Established and early passage melanoma cells transfected with human IFN-gamma complementary DNA (cDNA) produced IFN-gamma (50-5,000 pg/mL). The biological effect of this IFN-gamma transgene included an upregulation, or de novo appearance, of HLA expression. These melanoma cells had no detectable baseline surface expression of the B7-1 costimulatory molecule, but 8% to 31% of these cells became B7-1 positive with no selection procedure after gene transfer with human B7-1 cDNA. After combination gene transfer with cDNAs for both IFN-gamma and B7-1, 9% to 33% of these cells expressed both HLA-DR and B7-1. In combination gene transfer experiments with cDNAs for both HLA-A2 and B7-1, dual expression of HLA-A2 and B7-1 was achieved in 10% to 17% of the melanoma cells. Thus, the molecular modification of human melanoma cells to increase expression of both HLA and B7-1 can be achieved by particle-mediated gene delivery and presents a promising strategy to stimulate antimelanoma T-cell immunity. Key words: Melanoma; T cells; B7-1 costimulatory molecule (CD80); major histocompatibility complex.

Measurement of tumour size in case selection for breast cancer therapy by clinical assessment and ultrasound.

AIMS: Clinical assessment of tumour size is often used to choose between mastectomy and primary medical therapy. Clinical and imaging modalities may have varying levels of accuracy across the range of tumour sizes. The aim of this study was to compare the accuracy of clinical measurement and ultrasound in discriminating palpable tumours up to 3 cm vs those greater than 3 cm. METHODS: A prospective analysis of 111 consecutive patients with palpable breast cancer was performed. All women had clinical measurement by caliper and ultrasound assessment prior to any needle biopsy. Clinical measurement and ultrasound assessment of size were compared to pathological tumour size of the surgical specimen. RESULTS: Both clinical and ultrasound measurement underestimate the size of larger tumours. The overall accuracy of clinical assessment and ultrasound examination in correctly identifying a 30 mm cut off was 70.3 and 77.5%, respectively. Ultrasound was significantly more accurate at determining the size of tumours <30 mm (p=0.007) but there was no significant difference between both modalities in assessing tumours greater than 30 mm. CONCLUSIONS: Ultrasound assessment of breast cancer size is more accurate than clinical assessment for tumours less than 30 mm. As clinical examination is as accurate on ultrasound for tumours greater than 30 mm, clinical assessment of tumour size alone is adequate to select patients for primary medical therapy or mastectomy.

The use of ultrasound by breast surgeons in outpatients: an accurate extension of clinical diagnosis.

AIMS: To assess the accuracy of breast ultrasound scan (USS) performed by a surgeon in outpatients and to evaluate the additional contribution of USS to clinical diagnosis. METHODS: A prospective study of 302 patients with symptomatic breast disease (322 lumps) was performed. Group 1 consisted of 213 clinic USS of lumps surgically removed for appropriate clinical indications. In Group 2, a USS was performed on 231 lumps by both the surgeon and radiologists as part of triple assessment. Each clinic USS was compared to the surgical pathology (Group 1) or USS performed by the radiologist (Group 2). RESULTS: In Group 1 (n=213), 89 lumps were proven benign and 124 malignant on histology. Ultrasound scans performed by the surgeon compared to histology had a sensitivity of 98.3% and specificity of 91.7%. An abnormal clinic USS heightened the index of suspicion in 22/213 (10.3%) of cases felt clinically to be benign but subsequently confirmed malignant on histology. Fifty-seven lumps felt to be indeterminate clinically were correctly identified on USS by surgeon as benign (n=56) or malignant (n=1). In Group 2 (n=231), there was complete concordance of USS scans by surgeon and radiologists in 197 (96%) and complete discordance in eight (3.9%) patients. Of the discordant scans, the surgeon correctly identified 7/8 diagnoses on histology. A USS examination by the radiologists provided a correct diagnosis of 6/14 scans scored by the clinician as indeterminate. CONCLUSION: USS performed in outpatients by a breast surgeon is accurate and a useful adjunct to clinical assessment. This enables rapid diagnosis in one-stop breast clinics, selecting difficult diagnostic procedures for USS by radiologists at the same visit.

A retrospective study comparing the individual modalities of triple assessment in the pre-operative diagnosis of invasive lobular breast carcinoma.

AIMS: Early invasive lobular breast carcinoma (ILC) is associated with few symptoms and signs. The individual sensitivity of clinical examination, mammography, ultrasonography, cytology and core biopsy have each been reported to be of limited value. The aim of this study was to evaluate the accuracy of triple assessment in the pre-operative detection of patients identified to have ILC from their surgical pathology. METHODS: Pure ILC was defined as tumours containing at least 90% lobular features. The triple assessment of 273 patients diagnosed primarily at our institution were reviewed. RESULTS: 87.5% of women were symptomatic and 12.5% were screen detected. The mean patient age was 59 (range 30-81) years and the median tumour size was 26 (range 5-110) mm. The main mammographic abnormalities were a spiculated lesion (33.3%), an ill-defined mass (33.3%) or architectural distortion (23.5%). The sensitivities for detecting ILC of each modality were: clinical examination (76.6%), mammography (79.8%), ultrasound examination (93.9%), fine-needle aspiration cytology (FNAC) (60.5%) and core biopsy (90.8%). Combining the three modalities of clinical examination, imaging and cyto/pathology increased the pre-operative detection rate of ILC. CONCLUSION: Triple assessment is useful in the diagnosis of ILC. As the features of ILC may be subtle, a high index of suspicion is required to facilitate early diagnosis.

Concentration-dependent, temperature-dependent non-Newtonian viscosity of lung surfactant dispersions.

The bulk shear viscosities of aqueous dispersions of lavaged calf lung surfactant (LS) and its chloroform:methanol extract (CLSE) were measured as a function of concentration, shear rate and temperature. At 10-mg phospholipid per milliliter, dispersions of LS and vortexed CLSE in 0.15 M NaCl (saline) had low viscosities near 1 cp over a range of shear rates from 225 to 1125 s(-1). Lung surfactant viscosity increased with phospholipid concentration and became strongly non-Newtonian with higher values at low shear rates. At 37 degrees C and 40 mg/ml, LS and vortexed CLSE in saline had viscosities of 38 and 34 cp (77 s(-1)) and 12 and 7 cp (770 s(-1)), respectively. Viscosity values for LS and CLSE were dependent on temperature and, at fixed shear, were lower at 23 degrees C than at 37 or 10 degrees C. Hysteresis was also present in viscosity measurements depending on whether shear rate was successively increased or decreased during study. Addition of 5 mM Ca(2+) at 37 degrees C markedly reduced CLSE viscosity at all shear rates and decreased LS viscosity at low shear rates. Dispersion by sonication rather than vortexing increased the viscosity of CLSE at fixed shear, while synthetic phospholipids dispersed by either method had low, relatively Newtonian viscosities. The complex viscous behavior of dispersions of LS and CLSE in saline results from their heterogeneous aggregated microstructure of phospholipids and apoproteins. Viscosity is influenced not only by the aggregate surface area under shear, but also by phospholipid-apoprotein interactions and aggregate structure/deformability. Similar complexities likely affect the viscosities of biologically-derived exogenous surfactant preparations administered to patients in clinical surfactant therapy.

In vivo mutant frequency of thioguanine-resistant T-cells in the peripheral blood and lymph nodes of melanoma patients.

T-cell activation by malignant melanoma would be anticipated to stimulate T-cell proliferation, which in turn has been associated with increasing the likelihood of somatic gene mutation. The purpose of this study was to test the hypothesis that in vivo hypoxanthine guanine phosphoribosyltransferase (hprt) mutant frequencies (MFs) are increased in peripheral blood T-cells from melanoma patients compared to normal controls. Assays were made of 48 peripheral blood samples from melanoma patients with stage 3 (13 patients) and stage 4 (35 patients) disease, 38 normal controls, and of nine tumor bearing lymph nodes. The mean hprt log(10)(MF) in patient peripheral blood was -4.77 (geometric mean hprt MF=17.0x10(-6)) compared to a mean hprt log(10)(MF) of -4.87 (geometric mean hprt MF=13.5x10(-6)) in controls. Although modest, this difference is statistically significant both by t-test (P=0.049) and after adjustment for covariates of age, gender, and cigarette smoking by regression analysis (P=0.001). Among the melanoma patients, the mean log(10)(MF) for the 17 patients who had received potentially genotoxic therapies was not significantly different from the mean log(10)(MF) for the 31 patients not receiving such therapies. The hprt MFs in the nine tumor bearing nodes were compared with MFs in peripheral blood from the same patients and revealed a non-significant (P=0.07) trend for increasing MFs in blood. Furthermore, analyses of T-cell receptor gene rearrangement patterns revealed hprt mutants originating from the same in vivo clone in both peripheral blood and a tumor-bearing node. The finding of elevated hprt MFs not entirely explained by genotoxic therapies in patients compared to controls can be explained either by hypermutability or in vivo T-cell activation. The similar MFs in peripheral blood and tumor bearing lymph nodes, as well as the finding of mutant representatives of the same in vivo T-cell clone in both locations, support monitoring peripheral blood to detect events in the nodes. If in vivo proliferation accounts for the current findings, the hprt deficient (hprt-) mutant fraction in blood may be enriched for T-cells that mediate the host immune response against malignant melanoma. Further studies will characterize the functional reactivity of hprt mutant isolates against melanoma-related antigens.

Gentamicin iontophoresis in the treatment of bacterial otitis externa in the guinea pig model.

Pseudomonas otitis externa is one of the most common infections treated by otolaryngologists. Infections induced in 30 guinea pigs appeared similar to that seen in humans. The ears were then placed into four treatment groups: group A, which received a single cleaning; group B, which received a single cleaning followed by gentamicin drops 4 times daily; group C, which received a single cleaning followed by a single gentamicin iontophoresis treatment; and group D, the control group, which received no treatment. Infections were analyzed by grading edema, purulence, and erythema. An average of 10.2 days was required for control group to return to normal appearance. Groups A, B, and C had mean resolution times of 5.9, 4.7, and 4.3 days, respectively. Gentamicin iontophoresis appears to be promising, with results as good as drop therapy in otitis externa in the guinea pig model.

Ultrasound diagnosis of metastatic melanoma of the gallbladder.

The abdominal ultrasound examinations of 464 patients with malignant melanoma performed over a 3 year period were reviewed. 23 (5.2%) had soft tissue material attached to the gallbladder wall and projecting into the lumen. Four of these were polyps of less than 1 cm which were thought to be benign, while the remaining 19 had abnormalities likely to be metastatic melanoma. Upper abdominal ultrasound examinations are frequently requested for staging purposes in patients with thick high grade malignant melanoma or clinical suspicion of metastases. Ultrasound clearly identifies the gallbladder and biliary tree in the vast majority of patients and is generally regarded as the imaging modality of choice for suspected gallbladder pathology. As autopsy studies have confirmed the incidence of gallbladder metastases from malignant melanoma to be 15-20%, a careful review of the gallbladder is advocated when abdominal ultrasound examinations are performed on patients with malignant melanoma.

Right atrial metastatic melanoma detected by dynamic contrast enhanced spiral CT.

The use of and transoesophageal echocardiography has been well described in the diagnosis of intracardiac metastases. We present a case of a right atrial mass in a patient with metastatic melanoma which was unexpectedly detected by dynamic enhanced spiral CT. The diagnosis was subsequently confirmed by MRI. It is likely that the increasingly widespread use of spiral CT will result in a greater detection rate of intracardiac tumours.

Benign metastasizing leiomyoma with intracaval leiomyomatosis.

We present an unusual case of benign metastasizing leiomyoma in association with intracaval leiomyomatosis. To our knowledge, this is the first reported case of metastasizing leiomyoma with coexistent intravenous leiomyomatosis (IVL). Magnetic resonance imaging is useful for the diagnosis of pelvic and caval IVL.

An alternative method of bowel preparation for barium enemas.

A double blind trial is described comparing two methods of bowel preparation prior to barium enema. In 40 randomly selected patients a significant improvement was obtained by the use of an intestinal perfusion method.