Pharmaceutical and Endocrine Disruptor Compounds in Surface and Wastewater in San Marcos, Texas.

Water resource recovery facilities (WRRFs) and hospitals are major point sources of pharmaceuticals and endocrine disrupting compounds (EDCs) in aquatic environments. This study investigated the removal efficiencies of 23 known or suspected EDCs through the San Marcos WRRF to determine which treatment process was the most effective at removal. Results from samples collected at the hospital indicate that the hospital discharge is contributing to the concentration of these compounds in the San Marcos wastewater collection system (0.05-140 µg/L concentrations). The most frequently detected compounds in the WRRF influent included acetaminophen, nonylphenol, caffeine, benzophenone, N,N-diethyl-m-toluamide (DEET), bisphenol A (BPA), and triclosan. Comparison of influent and effluent concentrations showed that the San Marcos WRRF is effectively removing (>92%) of these compounds, with the exception of carbamazepine and tris(2-chloroethyl) phosphate (TCEP). These preliminary results will be used to guide future improvements within the WRRF.

The cost of teaching an intern in New South Wales.

OBJECTIVE: To determine the cost of formal and informal teaching specifically provided for interns and to determine how much of an intern's time is spent in these activities. DESIGN, SETTING AND PARTICIPANTS: Costs of formal teaching for 2012 were obtained from the New South Wales Health Education and Training Institute (HETI) and costs of informal teaching by a survey of all interns in a random sample of prevocational networks. MAIN OUTCOME MEASURES: The cost of formal intern education provided by HETI; the number of hours of formal teaching provided to interns in hospital; intern estimates of the amount of non-timetabled teaching received in a typical week. RESULTS: The cost of formal teaching was $11 892 per intern per year and the cost of informal teaching was $2965 per intern per year (survey response rate, 63%) - a total of $14 857. Interns spent 2 hours per week in formal teaching and 28 minutes per week in informal teaching, representing 6.2% of a 40-hour week. CONCLUSION: The time of professionals paid by NSW Health represents most of the expenditure on teaching interns. An increase in time spent on intern teaching beyond the current 6.2% of an intern's 40-hour week would be an investment in better health care.

An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y.

In humans, deletion of any one of three Y-chromosomal regions- AZFa, AZFb or AZFc-disrupts spermatogenesis, causing infertility in otherwise healthy men. Although candidate genes have been identified in all three regions, no case of spermatogenic failure has been traced to a point mutation in a Y-linked gene, or to a deletion of a single Y-linked gene. We sequenced the AZFa region of the Y chromosome and identified two functional genes previously described: USP9Y (also known as DFFRY) and DBY (refs 7,8). Screening of the two genes in 576 infertile and 96 fertile men revealed several sequence variants, most of which appear to be heritable and of little functional consequence. We found one de novo mutation in USP9Y: a 4-bp deletion in a splice-donor site, causing an exon to be skipped and protein truncation. This mutation was present in a man with nonobstructive azoospermia (that is, no sperm was detected in semen), but absent in his fertile brother, suggesting that the USP9Y mutation caused spermatogenic failure. We also identified a single-gene deletion associated with spermatogenic failure, again involving USP9Y, by re-analysing a published study.

The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.

Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping-sequencing process. A complex of three palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from six distinct families of amplicons, with unit lengths of 115-678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. Deletions of AZFc that cause infertility are remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably served as substrates for homologous recombination.

The hidden cost of medical student education: an exploratory study.

OBJECTIVE: To examine the hidden cost of medical education at the Sydney Medical School, for which the University of Sydney does not pay. METHODS: All face-to-face teaching provided for students in the Sydney University Postgraduate Medical Program was listed under two headings: teaching by university employed staff; and teaching by other health providers not paid by the university. All teaching hours in 2010 were extracted from detailed timetables and categorised under these headings. Time spent in lecture preparation and exam marking was included. Students were sampled to obtain information about additional teaching that was not timetabled. RESULTS: Teaching by university paid staff accounted for 59 and 61% of face-to-face teaching costs in years 1 and 2 of the 4-year Graduate Program, but only 8% in the final 2 years. The cost of medical education provided by the university, including infrastructure costs was $56250 per student per year in 2010. An additional $34326 worth of teaching per student per year was provided by teachers not paid by the university. CONCLUSION: The true cost of medical education is the cost of education met by the university plus the value of teaching currently provided by government funded health providers and honorary teachers. In 2010, 38% of the medical education cost at Sydney University was provided at no cost to the University. As government health departments seek to trim rising health expenditure, there is no guarantee that they will continue to contribute to medical education without passing this cost on to universities. WHAT IS KNOWN ABOUT THIS TOPIC? Some medical student teaching is provided by teachers who may be employed by a government health provider or who are honorary teachers. There is no cost to the university for this teaching. WHAT DOES THIS PAPER ADD? An estimate of the total value of teaching provided to students at Sydney Medical School, for which the university does not pay, is approximately $34000 per student per year, compared with the total cost of approximately $56000 per student per year incurred by the university. WHAT ARE THE IMPLICATIONS? Medical education is a partnership between the university, the government health sector and honorary teachers. Without contributions by non-university paid staff, the cost of medical education would be unsustainable.

Child sexual abuse in the Anglican Church of Australia.

This article reports on a retrospective study of cases of child sexual abuse complaints made against clergy, other employed pastoral staff, and volunteers in the Anglican Church of Australia between 1990 and 2008. There were 191 allegations of sexual abuse made by 180 complainants against 135 individuals. Twenty-seven of those 135 had more than one complaint made against them. Three-quarters of all complainants were male. The most likely explanation for the large proportion of abused males is that the church gives many more opportunities for abusers to be alone with boys than with girls. Prevention strategies need to focus on reducing the opportunities for abuse to occur as well strategies concerning the recruitment of professional staff and volunteers.

Role of Brownian Particle Velocity in Bioelectronic Emissions of DNA.

Hypothesis: If double stranded DNA (dsDNA) is a charged biomolecule that moves in Earth's magnetic field at a Brownian velocity, then dsDNA may emit bioelectromagnetic waves at energies that reflect discrete genetic states. Methods: This work leverages the Planck-Einstein-de Broglie relationship and applies this concept to Brownian velocity of dsDNA within a cell, to describe the relationship between dsDNA mass, the average Brownian velocity of dsDNA within a cell, and the theoretical wavelengths at which DNA may emit bioelectromagnetic waves. Results: Theoretical emission wavelengths of dsDNA, derived from first principles, were found to correlate closely with experimentally observed emission wavelengths from spectroscopic measurements across various cellular systems in the literature. Conclusion: This work provides a conceptual basis for the potential for unification of bioelectromagnetism with Brownian motion, to elucidate how electromagnetic information can be generated at a subcellular level in biological systems. The implications of how finite mass changes in dsDNA can result in discrete emission wavelengths on electromagnetic timescales is discussed through the lens of genomics. Future refinements of this fundamental methodology may provide a conceptual basis to address previously unexplained multilevel phenomena in the field of biology and is general enough to be extended to other charged biomolecules at a subcellular level. Further exploration in this area could lead to new biological tool development that may augment current genomics methods.

Carbon nanotubes affect early growth, flowering time and phytohormones in tomato.

Carbon nanotube (CNT) applications are increasing in consumer products, including agriculture devices, making them an important contaminant to study in the field of plant nanotoxicology. Several studies have observed the uptake and effects of CNTs in plants. However, in other studies differing results were observed on growth and physiology depending on the plant species and type of CNT. This study focused on the effects of CNTs on plant phenotype with growth, time to flowering, fruiting time as endpoints, and physiology, through amino acid and phytohormone content, in tomato after exposure to multiple types of CNTs. Plants grown in CNT-contaminated soil exhibited a delay in early growth and flowering (especially in treatments of 1 mg/kg multi-walled nanotubes (MWNTs), 10 mg/kg MWNTs, and 1 mg/kg MWNTs-COOH). However, CNTs did not affect plant growth or height later in the life cycle. No significant differences in abscisic acid (ABA) and citrulline content were observed between the treated and control plants. However, single-walled nanotube (SWNT) exposure significantly increased salicylic acid (SA) content in tomato. These results suggest that SWNTs may elicit a stress response in tomatoes. Results from this study offer more insight into how plants respond and acclimate to CNTs. These results will lead to a better understanding of CNT impact on plant phenotype and physiology.

Matrix-matched standards in the liquid chromatography-mass spectrometry determination of neonicotinoids in soil and sediment.

The use of matrix-matched standards with a solid-liquid extraction and salting out without the addition of further cleanup steps or costly cleanup procedures associated with the quick, easy, cheap, effective, robust, and safe (QuEChERS) method was evaluated to address variations in ionization efficiency in the LC-MS/MS determination of neonicotinoid pesticides in complex environmental samples. Limits of detection (1.4-3.4 ng/g) and limits of quantitation (4.6-11.3 ng/g) for various neonicotinoid analogs were comparable to previously reported QuEChERS extraction methods. Mean recovery of standard neonicotinoid samples spiked with 10 ng/g was found to be 78.0-100.5%, while samples spiked with 100 ng/g were found to be 55.1-99.9%. Recovery of analytes was matrix dependent; the highest recovery was from sediment (86.2-100.5%) followed by laboratory sand (70.9-81.7%) and agricultural soil (55.5-102.6%), respectively. Optimization of this methodology resulted in the reduction of procedure time and cost, and can aid in environmental monitoring efforts of common neonicotinoid pesticides in soils and sediments.

Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion.

Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian cancer patients, but its potential role in ovarian cancer metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary ovarian cancer cells, but not ovarian epithelial or borderline ovarian tumor cells, although these benign cells indeed respond to LPA in cell migration. We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators. G(i) protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), cytosolic phospholipase A(2) and urokinase type plasminogen activator (uPA) are required for LPA-induced cells invasion. TIMP3 may affect two independent downstream targets, vascular endothelial growth factor receptor and p38 MAPK. In vivo, LPA stimulates tumor metastasis in an orthotopic ovarian tumor model, which can be inhibited by a PI3K inhibitor, LY294002. In summary, LPA is likely a key component for promoting ovarian metastasis in vivo. LPA downregulates TIMP3, which may have targets other than metalloproteinases. Our in vivo metastasis mouse model is useful for studying the efficacy of therapeutic regimes of ovarian cancer.

Development of primary standards for mass spectrometry to increase accuracy in quantifying environmental contaminants.

Internal standards are essential in electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS) to correct for systematic error associated with ionization suppression and/or enhancement. A wide array of instrument setups and interfaces has created difficulty in comparing the quantitation of absolute analyte response across laboratories. This communication demonstrates the use of primary standards as operational qualification standards for LC-MS instruments and their comparison with commonly accepted internal standards. In monitoring the performance of internal standards for perfluorinated compounds, potassium hydrogen phthalate (KHP) presented lower inter-day variability in instrument response than a commonly accepted deuterated perfluorinated internal standard (d3-PFOS), with percent relative standard deviations less than or equal to 6%. The inter-day precision of KHP was greater than d3-PFOS over a 28-day monitoring of perfluorooctanesulfonic acid (PFOS), across concentrations ranging from 0 to 100µg/L. The primary standard trometamol (Trizma) performed as well as known internal standards simeton and tris (2-chloroisopropyl) phosphate (TCPP), with intra-day precision of Trizma response as low as 7% RSD on day 28. The inter-day precision of Trizma response was found to be greater than simeton and TCPP, across concentrations of neonicotinoids ranging from 1 to 100µg/L. This study explores the potential of primary standards to be incorporated into LC-MS/MS methodology to improve the quantitative accuracy in environmental contaminant analysis.

Biophysical Viscosity: Thermodynamic Principles of Per Capita Chemical Potentials in Human Populations.

Dynamic viscosity has been used to describe molecular resistance to flow under an applied force. This study introduces the theory of biophysical viscosity, the resistance of a region to molecular flow under environmental force to define the rates of per capita anthropogenic chemical efflux into the environment. Biophysical viscosity is an important intermediate quantity, in that it can be used to calculate the chemical potentials of single molecules for individuals in a population. Nonhypothetical emission data was combined with chemical potentials of anthropogenic tracers, to demonstrate that thermodynamic quantities can be used as parameters to directly compare energies associated with individual chemical emissions across geographic regions. These results indicate that population density is not the only factor in the determination of population-level chemical efflux and that biophysical viscosity is a useful tool in determining the per capita chemical potentials of anthropogenic chemicals for environmental risk assessment.

Real-time Image-guided Adaptive-predictive Prostate Radiotherapy using Rectal Diameter as a Predictor of Motion.

AIMS: To investigate a relationship between maximum rectal diameter (MRD) on pre-treatment cone beam computed tomography (CBCT) and intra-fraction prostate motion, in the context of an adaptive image-guided radiotherapy (IGRT) method. MATERIALS AND METHODS: The MRD was measured on 2125 CBCTs from 55 retrospective patient datasets and related to prostate displacement from intra-fraction imaging. A linear regression model was developed to determine a threshold MRD associated with a high probability of small prostate displacement. Standard and reduced adaptive margin plans were created to compare rectum and bladder normal tissue complication probability (NTCP) with each method. RESULTS: A per-protocol analysis carried out on 1910 fractions from 51 patients showed with 90% confidence that for a MRD≤3 cm, prostate displacement will be ≤5 mm and that for a MRD≤3.5 cm, prostate displacement will be ≤5.5 mm. In the first scenario, if adaptive therapy was used instead of standard therapy, median reductions in NTCP for rectum and bladder were 0.5% (from 9.5% to 9%) and 1.3% (from 6.6% to 5.3%), respectively. In the second scenario, the NTCP for rectum and bladder would have median reductions of 1.1% and 2.6%, respectively. CONCLUSIONS: We have identified a potential method for adaptive prostate IGRT based upon predicting small prostate intra-fraction motion by measuring MRD on pre-treatment CBCT.

A Multidisciplinary Evaluation of a Web-based eLearning Training Programme for SAFRON II (TROG 13.01): a Multicentre Randomised Study of Stereotactic Radiotherapy for Lung Metastases.

AIMS: In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites. MATERIALS AND METHODS: A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale. RESULTS: In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P < 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (>4 weeks) after completing the modules (P < 0.001). For most there was significant increase in confidence (P < 0.001) after completing all the modules.

Postchemotherapy ejaculatory azoospermia: fatherhood with sperm from testis tissue with intracytoplasmic sperm injection.

PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patients fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis was performed in all patients. The presence or absence of sperm, fertilization rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS: Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the predominant pattern observed was Sertoli cell only (47.8%), followed by hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%). The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in 30.8% of cycles. Six healthy boys and four healthy girls have been born to date. CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up a small subgroup of males with nonobstructive azoospermia. It is important to define and characterize this subgroup and better define their true fertility potential. Approximately two thirds of these men have retrievable testis sperm, which may be used with ICSI to have healthy offspring. This exciting avenue for paternity has heretofore not been available to such patients.

The effect of spinal cord level on sexual function in the spina bifida population.

INTRODUCTION: Sexual dysfunction and infertility are prevalent in the spina bifida (SB) population; however, the mechanism of how they affect a person with spina bifida is poorly understood. Additionally, the management of children with spina bifida becomes more difficult as they exit from pediatric institutes. OBJECTIVE: The present study sought to evaluate sexual health (using validated questionnaires) and fertility in adults with spina bifida and to correlate spinal cord level and ambulatory status with degree of sexual function. STUDY DESIGN: After institutional board review approval, 199 adult patients with SB, aged 18 and older and who were followed in one pediatric institution, were identified. Patients who were non-English speaking, cognitively and/or developmentally delayed, or unable to be contacted were excluded. Surveys regarding demographics, sexual health and infertility were mailed to the patients and administered in the clinic with the option to opt-out of the survey. Survey questions regarding sexual health were constructed using validated questionnaires: Female Sexual Function Index (FSFI) for females, and International Index of Erectile Function (IIEF) and Sexual Health Inventory for Men (SHIM) for males. Sexual dysfunction scores were correlated to the patients' spinal level and ambulatory status. RESULTS: Of the 121 eligible patients, 45 replied, with a response rate of 39%. For females, using a cut-off value of 26.5 for FSFI scoring, 25 out of 28 (89%) had sexual dysfunction. No association was seen between spinal level or ambulatory status and overall FSFI, satisfaction, or desire scores. For males, 10 out of 17 (59%) had severe erectile dysfunction (ED), and one out of 17 (6%) had no ED. No association was seen between ambulatory status and sexual function scores for the males. However, SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. People with spina bifida of both genders tended to have more severe dysfunction compared to those with sexual dysfunction of other etiologies, except with similar sexual desire scores. Regarding questions on fertility, no participant attempted to have children; thus, there was no infertility reported. DISCUSSION: Few studies have been conducted on sexual health and fertility in adults with SB. Three studies have utilized validated questionnaires and found varying degrees of sexual dysfunction in this subset of patients; however, only one study found sexual activity to be more likely in patients with more caudal levels of neurologic impairment. The present study also showed that SHIM, satisfaction, and ED scores were higher in males with lower spinal lesions. Limitations to this study primarily included the small sample size and low survey response rate. CONCLUSION: Limited information is known about adults with SB, and sexual function and fertility. While expressing sexual desire, adults with SB appear to experience high rates of sexual dysfunction. Fertility rates were inadequately assessed; this was possibly due to the high rate of sexual dysfunction. Sexual health in the SB population is an important component of the myriad of urologic care issues for these people. Due to the disparity in their care after reaching adulthood, it is prudent to follow these patients and understand their pathophysiology as they continue to mature through life.

Nonorganic failure to thrive: a long-term follow-up.

Twenty-one children diagnosed as having nonorganic failure to thrive were reviewed at an average of 6 years 4 months after their initial presentation. Most of the children were found to be of normal height and weight but disorders in personality traits and educational attainments were common. One half of the children have abnormal personalities. Two thirds have a delayed reading age. Intelligence testing shows that one third have verbal scores significantly lower than their performance scores. Two children from the original series have died in suspicious circumstances. The families of these children have a high incidence of marital instability and economic difficulties. The traditional medical approach to nonorganic failure to thrive needs to be complemented by intensive social support for these families at the time of initial presentation in the hope that the long-term effects of this syndrome can be ameliorated.