Using public participation to sample trace metals in lake surface sediments: the OPAL Metals Survey.

Members of the public in England were invited in 2010 to take part in a national metals survey, by collecting samples of littoral sediment from a standing water body for geochemical analysis. To our knowledge, this is the first national sediment metals survey using public participation and reveals a snapshot of the extent of metals contamination in ponds and lakes across England. Hg, Ni, Cu, Zn and Pb concentrations exceeding sediment quality guidelines for the health of aquatic biota are ubiquitous in ponds and lakes, not just in areas with a legacy of industrial activity. To validate the public sampling approach, a calibration exercise was conducted at ten water bodies selected to represent a range of lakes found across England. Sediment concentrations of Hg, Ni, Cu, Zn and Pb were measured in samples of soil, stream and littoral and deep water sediment to assess inputs. Significant differences between littoral sediment metal concentrations occur due to local variability, but also organic content, especially in upland, peat soil catchments. Variability of metal concentrations between littoral samples is shown to be low in small (<20 ha) lowland lakes. Larger and upland lakes with more complex inputs and variation in organic content of littoral samples have a greater variability. Collection of littoral sediments in small lakes and ponds, with or without voluntary participation, can provide a reliable sampling technique for the preliminary assessment of metal contamination in standing waters. However, the heterogeneity of geology, soils and history/extent of metal contamination in the English landscape, combined with the random nature of sample collection, shows that systematic sampling for evaluating the full extent of metal contamination in lakes is still required.

Quality control in public participation assessments of water quality: the OPAL Water Survey.

BACKGROUND: Public participation in scientific data collection is a rapidly expanding field. In water quality surveys, the involvement of the public, usually as trained volunteers, generally includes the identification of aquatic invertebrates to a broad taxonomic level. However, quality assurance is often not addressed and remains a key concern for the acceptance of publicly-generated water quality data. The Open Air Laboratories (OPAL) Water Survey, launched in May 2010, aimed to encourage interest and participation in water science by developing a 'low-barrier-to-entry' water quality survey. During 2010, over 3000 participant-selected lakes and ponds were surveyed making this the largest public participation lake and pond survey undertaken to date in the UK. But the OPAL approach of using untrained volunteers and largely anonymous data submission exacerbates quality control concerns. A number of approaches were used in order to address data quality issues including: sensitivity analysis to determine differences due to operator, sampling effort and duration; direct comparisons of identification between participants and experienced scientists; the use of a self-assessment identification quiz; the use of multiple participant surveys to assess data variability at single sites over short periods of time; comparison of survey techniques with other measurement variables and with other metrics generally considered more accurate. These quality control approaches were then used to screen the OPAL Water Survey data to generate a more robust dataset. RESULTS: The OPAL Water Survey results provide a regional and national assessment of water quality as well as a first national picture of water clarity (as suspended solids concentrations). Less than 10 % of lakes and ponds surveyed were 'poor' quality while 26.8 % were in the highest water quality band. CONCLUSIONS: It is likely that there will always be a question mark over untrained volunteer generated data simply because quality assurance is uncertain, regardless of any post hoc data analyses. Quality control at all stages, from survey design, identification tests, data submission and interpretation can all increase confidence such that useful data can be generated by public participants.

Elevated rates of prolonged grief disorder in African Americans.

The prevalence of Prolonged Grief Disorder (PGD) in non-Whites is currently unknown. This study was performed to explore the prevalence of PGD in African Americans (AAs). Multivariable analysis of two studies of recently bereaved individuals found AAs to have significantly higher rates of PGD than Whites (21% [14 of 66] vs. 12% [55 of 471], respectively; p = 0.03). Experiencing a loved one's death as sudden or unexpected was also significantly associated with PGD over and above the effects of race/ethnicity. AAs may be at increased risk for the development of PGD. The development of effective interventions to treat PGD highlights the need to identify high-risk individuals and refer them to therapy and suggests the potential need for such therapies to adopt culturally sensitive approaches to care.

Risk factors for cardiovascular disease in children with Type I diabetes.

BACKGROUND: The major cause of morbidity and mortality in individuals with Type I insulin-dependent diabetes mellitus (IDDM) is premature and extensive atherosclerotic cardiovascular disease (CVD). OBJECTIVES: To determine the prevalence and predictors of hypercholesterolemia and to examine the distribution and interrelationship of risk factors for CVD. METHODS: This observational (mixed-longitudinal) study, guided by an epidemiologic framework, assessed a sample of 140 children with IDDM. Total cholesterol (TC) and diabetes control were measured in the total sample. Standard CVD risk factors were measured in a subsample of 67 children. RESULTS: Observed frequency of TC greater than the 75th percentile and greater than the 95th percentile was significantly more than expected (p < 0.01 and p < 0.0001, respectively). In the total sample, TC-CVD risk factor associations were not observed. However, diabetes control and physical activity were correlated with TC in the risk sample of children at highest risk, as demonstrated by hypercholesterolemia. CONCLUSIONS: Results demonstrate the importance of assessing the lipid profile in children with IDDM and monitoring CVD risk factors in hyperlipidemic children with IDDM. Future research should focus on prospective longitudinal studies in population-based multiethnic samples of children with IDDM.

Five year results of LINAC radiosurgery for arteriovenous malformations: outcome for large AVMS.

PURPOSE: For radiosurgery of large arteriovenous malformations (AVMs), the optimal relationship of dose and volume to obliteration, complications, and hemorrhage is not well defined. Multivariate analysis was performed to assess the relationship of multiple AVM and treatment factors to the outcome of AVMs significantly larger than previously reported in the literature. METHODS AND MATERIALS: 73 patients with intracranial AVMs underwent LINAC radiosurgery. Over 50% of the AVMs were larger than 3 cm in diameter and the median and mean treatment volumes were 8.4 cc and 15.3 cc, respectively (range 0.4-143.4 cc). Minimum AVM treatment doses varied between 1000-2200 cGy (median: 1600 cGy). RESULTS: The obliteration rates for treatment volumes < 4 cc, 4-13.9 cc, and > or = 14 cc were 67%, 58%, and 23%, respectively. AVM obliteration was significantly associated with higher minimum treatment dose and negatively associated with a history of prior embolization with particulate materials. No AVM receiving < 1400 cGy was obliterated. The incidence of post-radiosurgical imaging abnormalities and clinical complications rose with increasing treatment volume. For treatment volumes > 14 cc receiving > or = 1600 cGy, the incidence of post-radiosurgical MRI T2 abnormalities was 72% and the incidence of radiation necrosis requiring resection was 22%. The rate of post-radiosurgical hemorrhage was 2.7% per person-year for AVMs with treatment volumes < 14 cc and 7.5% per person-year for AVMs > or = 14 cc. CONCLUSION: As AVM size increases, the dose-volume range for the optimal balance between successful obliteration and the risk of complications and post-radiosurgical hemorrhage narrows.

Teleoncology in the Department of Defense: a tale of two systems.

Two telemedicine networks were developed for the purpose of conducting multidisciplinary oncology ("teleoncology") conferences. The infrastructure of each system differed: one system was Internet-based; the other was delivered via Integrated Services Digital Network (ISDN) lines. The purpose of this study was to describe the infrastructure and cost, consultative process, technical aspects, and conference format of the two teleoncology programs. The two systems' technical aspects, participant satisfaction with the systems, and conference participation were compared qualitatively. Assessment of the technical aspects of the systems suggested that each had distinct advantages. Survey results indicated that provider satisfaction with the technical and logistical aspects of each type of teleoncology conference was high. The present study may prove helpful for individuals who are considering implementing their own teleoncology programs.

Transient association of the phosphotyrosine phosphatase SHP-2 with TrkA is induced by nerve growth factor.

Nerve growth factor (NGF) treatment of rat PC12 pheochromocytoma cells results in an increase in the tyrosine phosphorylation of the NGF receptor, TrkA, leading to differentiation to a neuronal phenotype. Dephosphorylation by protein tyrosine phosphatases (PTPases) is thought to play an important role in regulating this signaling pathway. To identify PTPases that are recruited to the activated TrkA receptor, we used an in-gel PTPase assay to examine the presence of PTPases in TrkA immunoprecipitates. The Src homology 2 domain containing PTPase SHP-2 was found to associate transiently with TrkA following receptor activation, reaching a peak after 1 min of NGF treatment and then decreasing rapidly. The association of SHP-2 with TrkA was accompanied by the tyrosine phosphorylation of SHP-2 and an association of SHP-2 with multiple tyrosine-phosphorylated proteins. In addition, the PTPase activity in SHP-2 immunoprecipitates increased greater than twofold after 1 min of NGF treatment. This is the first demonstration that the association of SHP-2 with TrkA is induced by NGF and that this association leads to SHP-2 activation and tyrosine phosphorylation. We conclude that SHP-2 plays a significant role in early biochemical events in TrkA-mediated signal transduction.

Phospholipase A2 and arachidonate increase in bronchoalveolar lavage fluid after inhaled antigen challenge in asthmatics.

Phospholipases A2 (PLA2) hydrolyze phospholipids resulting in the release of fatty acids including arachidonic acid (AA) and lysophospholipids. AA, in turn, serves as a substrate for the synthesis of leukotrienes which can cause bronchoconstriction and airways edema and appear to be important mediators of clinical asthma. Further, lysophospholipids may be cytotoxic and/or impair the function of surfactant. We examined the release of secretory PLA2 (sPLA2) and AA into the airways after antigen challenge in 16 subjects with allergic asthma. Asthmatic subjects underwent bronchoscopy with bronchoalveolar lavage (BAL) before and after inhaled antigen challenge; in addition, a single BAL, without inhaled antigen, was performed in 10 control subjects. BAL was obtained at 4 h (n = 7), the time of the late asthmatic response (LAR) (n = 5), or 24 h (n = 4) after challenge. There was no difference between normal and asthmatic subjects in either BAL fluid (BALF) sPLA2 activity or AA concentration at baseline. Both sPLA2 and AA increased after antigen challenge (p < 0.01 and 0.05, respectively). These changes were most marked 4 h after challenge (p < 0.03 for both). sPLA2 may play an important role in the generation of AA in patients with asthma.

Protein tyrosine phosphatases.

Protein tyrosine phosphatases (PTPases) balance the action of tyrosine kinases to maintain a set level of cellular tyrosine phosphorylation. Increases in tyrosine phosphorylation produced by transformation with constitutively active tyrosine kinases can initiate cellular proliferation. PTPases may act as tumor suppressors to counteract the transforming potential of oncogenic kinases. However, recent evidence suggests that PTPases have the potential to act as positive mediators of mitogenic signaling. If PTPases are acting as tumor suppressors, the expression of an inactive PTPase may cause an increase in overall tyrosine phosphorylation of cellular proteins, resulting in cellular transformation. Alternatively, overexpression of PTPases that play a positive role in signal transduction might also lead to proliferation. The role that each PTPase plays may depend in the cellular context in which it is expressed.

SHP-2 is involved in neurotrophin signaling.

To investigate the involvement of SHP-2 in the signal transduction pathway stimulated by neurotrophins, the association of SHP-2 with components of the pathway was examined. Following NGF stimulation of PC12 cells, SHP-2 was found to be associated with the p85 subunit of PI3-kinase and the Shc proteins. In retinoic acid-differentiated SH-SY5Y cells and primary cultures of rat cortical neurons, BDNF treatment similarly caused the association of SHP-2 with p85. In addition, a tyrosine-phosphorylated protein, which is probably TrkB, was coimmunoprecipitated with SHP-2 in both cultures. These results show that SHP-2 becomes associated with signaling proteins after treatment with neurotrophins and suggest that SHP-2 plays a fundamental role in neurotrophin signaling.

Pharmacokinetics of cyclosporine after renal transplant in children.

The pharmacokinetics of cyclosporine and the relationship between blood levels and average drug concentration were prospectively evaluated in 18 children 1 month after renal transplantation. All children had normal renal function and no hepatic or gastrointestinal dysfunction. Cyclosporine was administered after an overnight fast, and serial blood samples were drawn over a 24-hour period. Analysis of cyclosporine levels was performed by means of monoclonal radio immunoassay on whole blood. Children were divided into three age groups for comparison: 2-5 years, 5-10 years, and > 10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in the pharmacokinetic parameters of cyclosporine except as follows: significant differences were noted in cyclosporine dose based on body weight, apparent steady-state volume of distribution, and apparent blood clearance, with the youngest children (2-5) requiring higher doses, a relative greater distribution, and exhibiting more rapid drug clearance than those > 10 years of age. In addition, we observed diurnal variation in trough levels, with morning levels (0 hr) significantly higher than those obtained in the evening (12 hours after administration of cyclosporine). Trough levels demonstrated a fair correlation with area under the concentration-time curve (AUC) and average concentration (Cav), but an abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.

Effects of carbamazepine on cyclosporine metabolism in pediatric renal transplant recipients.

This study documents a pharmacokinetic interaction between carbamazepine and cyclosporine (CsA) in pediatric renal transplant recipients. Noncompartmental steady-state CsA pharmacokinetics were determined in three pediatric renal transplant recipients who were receiving both CsA and carbamazepine as long-term therapy (carbamazepine group) and in three matched renal transplant subjects who were not receiving carbamazepine (control group). Even though the mean daily dosage of CsA was consistently higher in the carbamazepine group than in the control group (16.2 mg/kg/24 hrs vs 10.8 mg/kg/24 hrs, respectively), the predose trough CsA blood concentrations were significantly lower in the carbamazepine group (57 ng/ml vs 162 ng/ml, respectively; p = 0.0023). Mean average steady-state blood concentrations of CsA (Cav) per mg of CsA administered were less than 50% in the carbamazepine group compared with the control group. This reflects either an induction of CsA hepatic metabolism or a reduced systemic bioavailability (possible induction of pre-hepatic metabolism) by concurrent use of carbamazepine.

Postoperative irradiation for subtotally resected meningiomas. A retrospective analysis of 140 patients treated from 1967 to 1990.

The authors retrospectively analyzed 140 patients treated at the University of California, San Francisco, from 1967 to 1990 to evaluate the results of radiation therapy (median 5400 cGy) given as an adjuvant to subtotal resection of intracranial meningioma. Of the 140 meningiomas, 117 were benign and 23 were malignant. The median follow-up period was 40 months. The overall survival rate at 5 years was 85% for the benign and 58% for the malignant tumor groups (p = 0.02); the 5-year progression-free survival rates were 89% and 48%, respectively (p = 0.001). For patients with benign meningioma, the 10-year overall and progression-free survival rates were 77%. An improved progression-free survival rate in that group was not related to tumor size but was associated with a younger age (p = 0.01) and treatment after 1980 with innovative technologies (p = 0.002); none of those variables affected the progression-free survival rate in the patients with malignant meningioma. Increased progression-free survival in the benign tumor group was also significantly associated with increasing the minimum radiation dose (p = 0.04). The 5-year progression-free survival rate for patients with benign meningioma treated after 1980 (when computerized tomography or magnetic resonance imaging was used for planning therapy) was 98%, as compared with 77% for patients treated before 1980 (p = 0.002). There were no second central nervous system tumors. Morbidity (3.6%) included sudden blindness or cerebral necrosis and death. When total resection of benign meningioma is not feasible, subtotal resection combined with precise treatment planning techniques and adjuvant radiation therapy can achieve results comparable to those of total resection.

Immobilization improves the reproducibility of patient positioning during six-field conformal radiation therapy for prostate carcinoma.

PURPOSE: To determine the magnitude of patient positioning errors associated with six field conformal therapy for carcinoma of the prostate, and to assess the impact of alpha-cradle immobilization on these errors. METHODS AND MATERIALS: The records of 22 patients, treated at two of the treatment facilities within our department, using computed tomography-planned conformal six field therapy for carcinoma of the prostate, were reviewed. At one facility (UCD), patients were routinely treated with immobilization, while at the other (UCSF) no rigid immobilization was used. Portal films of patients treated at both facilities were subsequently reviewed, and the deviation of each portal from the simulation film was determined (simulation-to-treatment variability). In addition, for each patient, the average deviation of each portal film from the average portal film (treatment-to-treatment variability) was determined. RESULTS: The mean and median simulation-to-treatment variability was 0.4 cm for those patients treated with immobilization, versus 0.6 cm for those treated without immobilization. The 90th percentile of simulation-to-treatment variability was 0.7 cm for those patients treated with immobilization, versus 1.1 cm for those not immobilized. There was a significant reduction in the number of portals observed with errors of > or = 0.50 cm (132/201 vs. 37/87, 66% vs. 43%; p < 0.001), 0.75 cm (184/201 vs. 59/87, 92% vs. 68%; p < 0.001), and 1.0 cm (196/201 vs. 74/87, 98% vs. 85%; p < 0.001) for patients treated with immobilization. There was also a significant reduction in the number of patients with treatment-to-treatment variability > or = 0.5 cm (1/10 vs. 8/12; p = 0.01) for patients treated with immobilization. CONCLUSION: The use of immobilization devices significantly reduces errors in patient positioning, potentially permitting the use of smaller treatment volumes. Immobilization should be a component of conformal radiation therapy programs for prostate carcinoma.