Upstream Dispersion in Solute Transport Models: A Simple Evaluation and Reduction Methodology.

This article outlines analytical solutions to quantify the length scale associated with "upstream dispersion," the artificial movement of solutes in the opposite direction to groundwater flow, in solute transport models. Upstream dispersion is an unwanted artifact in common applications of the advection-dispersion equation (ADE) in problems involving groundwater flow in the direction of increasing solute concentrations. Simple formulae for estimating the one-dimensional distance of upstream dispersion are provided. These show that under idealized conditions (i.e., steady-state flow and transport, and a homogeneous aquifer), upstream dispersion may be a function of only longitudinal dispersivity. The scale of upstream dispersion in a selection of previously presented situations is approximated to highlight the utility of the presented formulae and the relevance of this ADE anomaly in common transport problems. Additionally, the analytical solution is applied in a hypothetical scenario to guide the modification of dispersion parameters to minimize upstream dispersion.

Improved Vertical Streambed Flux Estimation Using Multiple Diurnal Temperature Methods in Series.

Analytical solutions that use diurnal temperature signals to estimate vertical fluxes between groundwater and surface water based on either amplitude ratios (Ar ) or phase shifts (Δϕ) produce results that rarely agree. Analytical solutions that simultaneously utilize Ar and Δϕ within a single solution have more recently been derived, decreasing uncertainty in flux estimates in some applications. Benefits of combined (Ar Δϕ) methods also include that thermal diffusivity and sensor spacing can be calculated. However, poor identification of either Ar or Δϕ from raw temperature signals can lead to erratic parameter estimates from Ar Δϕ methods. An add-on program for VFLUX 2 is presented to address this issue. Using thermal diffusivity selected from an Ar Δϕ method during a reliable time period, fluxes are recalculated using an Ar method. This approach maximizes the benefits of the Ar and Ar Δϕ methods. Additionally, sensor spacing calculations can be used to identify periods with unreliable flux estimates, or to assess streambed scour. Using synthetic and field examples, the use of these solutions in series was particularly useful for gaining conditions where fluxes exceeded 1 m/d.

Optimizing geometric accuracy of four-dimensional CT scans acquired using the wall- and couch-mounted Varian® Real-time Position Management™ camera systems.

OBJECTIVE: The aim of this study was to identify sources of anatomical misrepresentation owing to the location of camera mounting, tumour motion velocity and image processing artefacts in order to optimize the four-dimensional CT (4DCT) scan protocol and improve geometrical-temporal accuracy. METHODS: A phantom with an imaging insert was driven with a sinusoidal superior-inferior motion of varying amplitude and period for 4DCT scanning. The length of a high-density cube within the insert was measured using treatment planning software to determine the accuracy of its spatial representation. Scan parameters were varied, including the tube rotation period and the cine time between reconstructed images. A CT image quality phantom was used to measure various image quality signatures under the scan parameters tested. RESULTS: No significant difference in spatial accuracy was found for 4DCT scans carried out using the wall- or couch-mounted camera for sinusoidal target motion. Greater spatial accuracy was found for 4DCT scans carried out using a tube rotation speed of 0.5 s rather than 1.0 s. The reduction in image quality when using a faster rotation speed was not enough to require an increase in patient dose. CONCLUSION: The 4DCT accuracy may be increased by optimizing scan parameters, including choosing faster tube rotation speeds. Peak misidentification in the recorded breathing trace may lead to spatial artefacts, and this risk can be reduced by using a couch-mounted infrared camera. ADVANCES IN KNOWLEDGE: This study explicitly shows that 4DCT scan accuracy is improved by scanning with a faster CT tube rotation speed.

Stochastic particle barcoding for single-cell tracking and multiparametric analysis.

This study presents stochastic particle barcoding (SPB), a method for tracking cell identity across bioanalytical platforms. In this approach, single cells or small collections of cells are co-encapsulated within an enzymatically-degradable hydrogel block along with a random collection of fluorescent beads, whose number, color, and position encode the identity of the cell, enabling samples to be transferred in bulk between single-cell assay platforms without losing the identity of individual cells. The application of SPB is demonstrated for transferring cells from a subnanoliter protein secretion/phenotyping array platform into a microtiter plate, with re-identification accuracies in the plate assay of 96±2%. Encapsulated cells are recovered by digesting the hydrogel, allowing subsequent genotyping and phenotyping of cell lysates. Finally, a model scaling is developed to illustrate how different parameters affect the accuracy of SPB and to motivate scaling of the method to thousands of unique blocks.

Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA.

STUDY QUESTION: Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe? SUMMARY ANSWER: Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels. WHAT IS KNOWN ALREADY: High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small sample size and the results have been contradictory. STUDY DESIGN, SIZE, DURATION: A coordinated international cross-sectional study among 8344 healthy men. A total of 1872 fertile men aged 18-45 years (with pregnant partners) from four European cities and four US states, and 6472 young men (most with unknown fertility) aged 18-28 years from the general population in six European countries were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS: The men were recruited using standardized protocols. A semen analysis was performed and men completed a questionnaire on health and lifestyle, including their intake of beer, wine and liquor during the week prior to their visit. Semen quality (semen volume, sperm concentration, percentage motile and morphologically normal sperm) and serum reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and inhibin B and free testosterone) were examined. MAIN RESULTS AND THE ROLE OF CHANCE: The participation rate for our populations was 20-30%. We found no consistent association between any semen variable and alcohol consumption, which was low/moderate in this group (median weekly intake 8 units), either for total consumption or consumption by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7 pmol/l (7.1-32.2) higher free testosterone than men with a weekly intake between 1 and 10 units. Alcohol intake was not significantly associated with serum inhibin B, FSH or LH levels in either group of men. The study is the largest of its kind and has sufficient power to detect changes in semen quality and reproductive hormones. LIMITATIONS, REASONS FOR CAUTION: The participation rate was low, but higher than in most previous semen quality studies. In addition, the study was cross-sectional and the men were asked to recall their alcohol intake in the previous week, which was used as a marker of intake up to 3 months before. If consumption in that week differed from the typical weekly intake and the intake 3 months earlier, misclassification of exposure may have occurred. However, the men were unaware of their semen quality when they responded to the questions about alcohol intake. Furthermore, we cannot exclude that our findings are due to unmeasured confounders, including diet, exercise, stress, occupation and risk-taking behavior. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels which may be due to a changed metabolism of testosterone in the liver. Healthy men may therefore be advised that occasional moderate alcohol intake may not harm their reproductive health; we cannot address the risk of high alcohol consumption of longer duration or binge drinking on semen quality and male reproductive hormones. STUDY FUNDING/COMPETING INTERESTS: All funding sources were non-profitable and sponsors of this study played no role in the study design, in data collection, analysis, or interpretation, or in the writing of the article. The authors have no conflicts of interest.

Improvement in clinical step and shoot intensity modulated radiation therapy delivery accuracy on an integrated linear accelerator control system.

PURPOSE: The dose delivery accuracy of 30 clinical step and shoot intensity modulated radiation therapy plans was investigated using the single integrated multileaf collimator controller of the Varian Truebeam linear accelerator (linac) (Varian Medical Systems, Palo Alto, CA) and compared with the dose delivery accuracy on a previous generation Varian 2100CD C-Series linac. METHODS AND MATERIALS: Ten prostate, 10 prostate and pelvic node, and 10 head-and-neck cases were investigated in this study. Dose delivery accuracy on each linac was assessed using Farmer ionization chamber point dose measurements, 2-dimensional planar ionization chamber array measurements, and the corresponding Varian dynamic log files. Absolute point dose measurements, fluence delivery accuracy, leaf position accuracy, and the overshoot effect were assessed for each plan. RESULTS: Absolute point dose delivery accuracy increased by 1.5% on the Truebeam compared with the 2100CD linac. No improvement in fluence delivery accuracy between the linacs, at a gamma criterion of 3%/3 mm was measured using the 2-dimensional ionization chamber array, with median (interquartile range) gamma passing rates of 98.99% (97.70%-99.72%) and 99.28% (98.26%-99.75%) for the Truebeam and 2100CD linacs, respectively. Varian log files also showed no improvement in fluence delivery between the linacs at 3%/3 mm, with median gamma passing rates of 99.97% (99.93%-99.99%) and 99.98% (99.94%-100%) for the Truebeam and 2100CD linacs, respectively. However, log files revealed improved leaf position accuracy and fluence delivery at 1%/1 mm criterion on the Truebeam (99.87%; 99.78%-99.94%) compared with the 2100CD linac (97.87%; 91.93%-99.49%). The overshoot effect, characterized on the 2100CD linac, was not observed on the Truebeam. CONCLUSIONS: The integrated multileaf collimator controller on the Varian Truebeam improves clinical treatment delivery accuracy of step and shoot intensity modulated radiation therapy fields compared with delivery on a Varian C-series linac.

Is γ-ray emission from novae affected by interference effects in the 18F(p,α)15O reaction?

The (18)F(p,α)(15)O reaction rate is crucial for constraining model predictions of the γ-ray observable radioisotope (18)F produced in novae. The determination of this rate is challenging due to particular features of the level scheme of the compound nucleus, (19)Ne, which result in interference effects potentially playing a significant role. The dominant uncertainty in this rate arises from interference between J(π)=3/2(+) states near the proton threshold (S(p)=6.411 MeV) and a broad J(π)=3/2(+) state at 665 keV above threshold. This unknown interference term results in up to a factor of 40 uncertainty in the astrophysical S-factor at nova temperatures. Here we report a new measurement of states in this energy region using the (19)F((3)He,t)(19)Ne reaction. In stark contrast to previous assumptions we find at least 3 resonances between the proton threshold and E(cm)=50 keV, all with different angular distributions. None of these are consistent with J(π)=3/2(+) angular distributions. We find that the main uncertainty now arises from the unknown proton width of the 48 keV resonance, not from possible interference effects. Hydrodynamic nova model calculations performed indicate that this unknown width affects (18)F production by at least a factor of two in the model considered.

Classical-NOVA CONTRIBUTION to the Milky Way's ²6Al abundance: exit channel of the key ²5Al(p,γ) ²6Si resonance.

Classical novae are expected to contribute to the 1809-keV Galactic γ-ray emission by producing its precursor 26Al, but the yield depends on the thermonuclear rate of the unmeasured 25Al(p,γ)26Si reaction. Using the ß decay of 26P to populate the key J(π)=3(+) resonance in this reaction, we report the first evidence for the observation of its exit channel via a 1741.6±0.6(stat)±0.3(syst) keV primary γ ray, where the uncertainties are statistical and systematic, respectively. By combining the measured γ-ray energy and intensity with other experimental data on 26Si, we find the center-of-mass energy and strength of the resonance to be E(r)=414.9±0.6(stat)±0.3(syst)±0.6(lit.) keV and ωγ=23±6(stat)(-10)(+11)(lit.) meV, respectively, where the last uncertainties are from adopted literature data. We use hydrodynamic nova simulations to model 26Al production showing that these measurements effectively eliminate the dominant experimental nuclear-physics uncertainty and we estimate that novae may contribute up to 30% of the Galactic 26Al.

Revised guidelines for cardiovascular risk management - time to stop medication? A practice-based intervention study.

BACKGROUND: According to the new Dutch guideline for cardiovascular risk management, patients with a low risk of cardiovascular mortality may have insufficient benefit to warrant medication. Therefore, numerous patients per general practice may be treated unnecessarily. AIM: To explore the feasibility and consequences of a re-evaluation programme for patients without target organ damage who were treated for hypertension and/or hypercholesterolaemia. DESIGN AND SETTING: Practice-based intervention study in six general practices. METHOD: Patients treated for hypertension and/or hypercholesterolaemia without target organ damage (n = 833) were invited to re-evaluate their cardiovascular risk and were advised whether or not to stop medication. Patients who discontinued medication were followed for 6 months. To determine indicators for successful stopping, logistic regression analyses were performed, and differences between practices were analysed. RESULTS: About two-thirds of the patients were re-evaluated and 61% of them had a low calculated risk, especially younger patients, females, and non-smokers. Of these, 42% were advised to stop medication, especially younger patients and non-smokers. Of those who discontinued medication, 40% had restarted within 6 months. After 6 months, 80 of the 833 patients (9.6%) had not restarted medication. There were no important side effects related to stopping medication. CONCLUSION: Over 50% of patients without target organ damage treated for hypertension and/or hypercholesterolaemia may have insufficient benefit to warrant medication. Younger patients, females, and non-smokers in particular are more likely to have an insufficient indication for medication. GPs' and nurse practitioners' views seem to play a role in advising to stop or to restart medication.

Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions.

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low-frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2-mm-wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response-area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low-frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo-cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low-frequency hearing.

Lack of impact of semen quality on fertilization in assisted conception.

BACKGROUND: Defective semen quality is one of the commonest causes of infertility. The diagnosis of male fertility depends upon a descriptive evaluation of human semen, however a normal semen analysis does not necessarily indicate satisfactory fertility potential. AIMS: (i) to examine the semen quality of patients undergoing treatment by assisted conception, (ii) to explore relationships between semen quality and treatment outcomes, and (iii) to look at inter-laboratory variation in the assessment of semen quality. METHODS: Semen quality in patients undergoing assisted conception treatment between 2001 and 2004 was reviewed. Data on female age, egg numbers and fertilization outcomes was obtained by case note review. RESULTS: The thresholds used to direct patients towards IVF or ICSI treatment were comparable with the normal values promulgated by WHO, with the exception of morphology. Semen quality was not predictive of fertilization rates. When the results of independent measurements of the same sample were compared, there was diagnostic disagreement in between 10%-29% of samples. CONCLUSIONS: The conventional criteria of semen quality are used to determine treatment strategy for couples undergoing assisted conception but are not reflected in fertilization rates, emphasising the limited utility of the conventional criteria of semen quality in the assessment of sperm function. There remains significant inter-laboratory variation in the results of semen analysis.

Serum inhibin-b in fertile men is strongly correlated with low but not high sperm counts: a coordinated study of 1,797 European and US men.

OBJECTIVE: To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported. DESIGN: Cross-sectional studies of spermatogenesis markers. SETTING: Four European and four US centers. PATIENT(S): Fertile men (1,797) were included and examined from October 1996-February 2005. INTERVENTION(S): The study was observational and therefore without any intervention. MAIN OUTCOME MEASURE(S): Associations between inhibin-b and semen variables controlled for time of blood sampling and other covariates. RESULT(S): Inhibin-b decreased about 2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm. There was a strong positive association between inhibin-b levels less than 150 pg/mL and both sperm concentration and total sperm count (slopes of the regression lines were ß=0.011 and ß=0.013 for natural logarithm-transformed sperm concentration and total sperm count, respectively). For inhibin-b levels of 150-300 pg/mL the associations were not as steep (ß=0.002), but still significant. For inhibin-b levels more than 300 pg/mL there was little association to the sperm counts. Neither sperm motility nor morphology was significantly related to inhibin-b level in any group. CONCLUSION(S): Serum inhibin-b levels decrease nonlinearly during the daytime, and are positively correlated with sperm counts, but the predictive power is best when inhibin-b is low.

Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database.

OBJECTIVE: To determine whether varenicline, a recently licensed smoking cessation product, is associated with an increased risk of suicide and suicidal behaviour compared with alternative treatments bupropion and nicotine replacement therapy. DESIGN: Cohort study nested within the General Practice Research Database. SETTING: Primary care in the United Kingdom. PARTICIPANTS: 80,660 men and women aged 18-95 years were prescribed a new course of a smoking cessation product between 1 September 2006 and 31 May 2008; the initial drugs prescribed during follow-up were nicotine replacement products (n=63 265), varenicline (n=10 973), and bupropion (n=6422). MAIN OUTCOME MEASURES: Primary outcomes were fatal and non-fatal self harm, secondary outcomes were suicidal thoughts and depression, all investigated with Cox's proportional hazards models. RESULTS: There was no clear evidence that varenicline was associated with an increased risk of fatal (n=2) or non-fatal (n=166) self harm, although a twofold increased risk cannot be ruled out on the basis of the upper limit of the 95% confidence interval. Compared with nicotine replacement products, the hazard ratio for self harm among people prescribed varenicline was 1.12 (95% CI 0.67 to 1.88), and it was 1.17 (0.59 to 2.32) for people prescribed bupropion. There was no evidence that varenicline was associated with an increased risk of depression (n=2244) (hazard ratio 0.88 (0.77 to1.00)) or suicidal thoughts (n=37) (1.43 (0.53 to 3.85)). CONCLUSION: Although a twofold increased risk of self harm with varenicline cannot be ruled out, these findings provide some reassurance concerning its association with suicidal behaviour.

A toxicity index of skin and wound cleansers used on in vitro fibroblasts and keratinocytes.

OBJECTIVE: To determine toxicity indexes of commercially available skin, wound, and skin/wound cleansers on in vitro fibroblasts and keratinocytes. DESIGN: Seventeen cleansers and 3 liquid bath soaps were evaluated for cytotoxic effect on human infant dermal fibroblasts and epidermal keratinocytes. Both skin cell types were exposed to serial 10-fold dilutions of each cleanser until treated cell viability was comparable to untreated controls. RESULTS: The experimental design allowed calculation of relative toxicity indexes ranging from 0 to 100,000. Shur-Clens, SAF-Clens, and saline were found to be the least toxic to fibroblasts (toxicity index 0); Dial Antibacterial Soap and Ivory Liqui-Gel were the most toxic (toxicity index 100,000). Biolex, Shur-Clens, and Techni-Care were the least toxic to keratinocytes (toxicity index 0); hydrogen peroxide, modified Dakin's solution, and povidone (10%) were found to be the most toxic (toxicity index 100,000). CONCLUSIONS: Successful cutaneous tissue repair depends on the viability of the principal cell types involved (fibroblasts and keratinocytes). Toxicity indexes provide helpful guidelines for subsequent in vivo evaluations and clinical applications. The study findings also suggest that judicious use of these supposedly innocuous agents should be considered in a clinical setting.

Brown recluse spider bites: a complex problem wound. A brief review and case study.

Brown recluse spiders (Loxosceles reclusa) are responsible for virtually all documented cases of spider bites leading to significant necrosis. The actual spider bite often goes unnoticed for as long as 4 to 6 hours, which makes diagnosis and, therefore, appropriate treatment, difficult. The spider bite generally results in either a necrotic wound or systemic symptoms that can lead to hemolysis. The patient described in this article experienced both complications. Dapsone and hyperbaric oxygen therapy brought the adverse response to the bite under control. The patient was hospitalized for 7 days during treatment for hemolysis and an extensive, necrotic wound. Efforts are underway to develop an assay to provide a definitive diagnosis for the brown recluse spider bite, but none is yet commercially available. Antivenom is scarce; capture of the offending spider appears to be most helpful in the diagnosis and proper treatment of spider bites.

Fertility preservation for young patients with cancer: who is at risk and what can be offered?

Estimates suggest that by 2010, one in 715 people in the UK will have survived cancer during childhood. With increasing numbers of children cured, attention has focused on their quality of life. We discuss the causes of impaired fertility after cancer treatment in young people, and outline which patients are at risk and how their gonadal function should be assessed. With the report of a livebirth after orthotopic transplantation of cryopreserved ovarian tissue and the continued development of intracytoplasmic sperm injection for men with poor sperm quality, we assess established and experimental strategies to protect or restore fertility, and discuss the ethical and legal issues that arise.

Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa.

An increase in scrotal temperature can lead to the production of poor quality spermatozoa and infertility. In the present study we have used mice to examine the impact of mild, scrotal heat stress (42 degrees C for 30 min) on numbers of spermatozoa as well as on the integrity of their DNA. Spermatozoa recovered from the epididymides hours (1 to 24) or days (7 to 32) after treatment were analysed using COMET and sperm chromatin structure (SCSA) assays. The treatment induced a stress response in both the testis and the epididymis that was associated with reduced expression of the cold inducible RNA binding protein (Cirp) and an increase in germ cell apoptosis (Apotag positive cells). Although spermatozoa present in the epididymis at the time of heating contained correctly packaged DNA, its integrity was compromised by heat stress. In addition, although some germ cells, which were present within the testis at the time of heat stress, were removed by apoptosis, many germ cells completed their development and were recovered as motile spermatozoa with damaged DNA. In conclusion, these data demonstrate that scrotal heat stress can compromise the DNA integrity of spermatozoa and this may have clinical implications for patients undergoing IVF and intra-cytoplasmic sperm injection (ICSI).

The influence of dispersant concentration on the pore morphology of hydroxyapatite ceramics for bone tissue engineering.

There is a clinical need for synthetic scaffolds that will promote bone regeneration. Important factors include obtaining an optimal porosity and size of interconnecting windows whilst maintaining scaffold mechanical strength, enabling complete penetration of cells and nutrients throughout the scaffold, preventing the formation of necrotic tissue in the centre of the scaffold. To address this we investigated varying slip deflocculation in order to control the resulting porosity, pore size and interconnecting window size whilst maintaining mechanical strength. Hydroxyapatite (HA) porous ceramics were prepared using a modified slip casting process. Rheological measurements of the HA slips were used to identify deflocculation conditions which resulted in changes in the cell and window sizes of the resulting ceramics. Sintered ceramics were characterised by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Pore and window size distribution was determined by SEM. XRD analysis confirmed that the crystal structure remained HA after the sintering process. SEM showed that HA porous ceramics presented a highly interconnected porous network with average pore sizes ranging from 391+/-39 to 495+/-25 microm. The average window size varied from 73+/-5 to 135+/-7 microm. Pore diameters obtained were controllable in the range 200-500 microm. Window sizes were in the range 30-250 microm. The use of dispersant concentration allows pore and window size to be modified whilst maintaining control over porosity demonstrated by a porosity of 85% for seven different dispersant concentrations. The advantage of this approach allows the correlation between the rheological conditions of the slip and the resultant sintered ceramic properties. In particular, optimising the ceramic strength by controlling the agglomeration during the casting process.