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The suitability of residue sand (the coarse fraction remaining from Bayer's process of bauxite refining) for constructing the surface cover of closed bauxite residue storage areas was investigated. Specifically, its properties as a medium for plant growth are of interest to ensure residue sand can support a sustainable ecosystem following site closure. The geochemical evolution of the residue sand under field conditions, its plant nutrient status and soil moisture retention were studied by integrated modelling of geochemical and hydrological processes. For the parameterization of mineral reactions, amounts and reaction kinetics of the mineral phases natron, calcite, tricalcium aluminate, sodalite, muscovite and analcime were derived from measured acid neutralization curves. The effective exchange capacity for ion adsorption was measured using three independent exchange methods. The geochemical model, which accounts for mineral reactions, cation exchange and activity corrected solution speciation, was formulated in the geochemical modelling framework PHREEQC, and partially validated in a saturated-flow column experiment. For the integration of variably saturated flow with multi-component solute transport in heterogeneous 2D domains, a coupling of PHREEQC with the multi-purpose finite-element solver COMSOL was established. The integrated hydrogeochemical model was applied to predict water availability and quality in a vertical flow lysimeter and a cover design for a storage facility using measured time series of rainfall and evaporation from southwest Western Australia. In both scenarios the sand was fertigated and gypsum-amended. Results show poor long-term retention of fertilizer ions and buffering of the pH around 10 for more than 5 y of leaching. It was concluded that fertigation, gypsum amendment and rainfall leaching alone were insufficient to render the geochemical conditions of residue sand suitable for optimal plant growth within the given timeframe. The surface cover simulation demonstrates that the soil moisture status in the residue sand can be ameliorated by an appropriate design of the cover layer with respect to thickness, slope and distance between lateral drains., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A new Fe- or Co-catalyzed Cl/Zn-exchange reaction allows the direct transformation of aryl, heteroaryl, and also alkyl chlorides into the corresponding zinc reagents. The method tolerates functional groups such as a nitrile or an ester. Remarkably, secondary and tertiary alkyl chlorides are suitable substrates for the Cl/Zn exchange., (© 2011 American Chemical Society)

The aryl sulfoxide moiety allows an expedient two-step difunctionalisation of readily available diaryl sulfoxides. Highly functionalised 1,2,4-trisubstituted arenes and difunctionalised heteroarenes (furans, thiophenes, benzofurans and pyridines) were prepared in a two-step sequence, triggered by an aryl sulfoxide group. In the first step, the sulfoxide moiety acts as a metallation-directing group, allowing smooth ortho-magnesiation with TMPMgCl⋅LiCl (TMP=tetramethylpiperidine). After a quenching reaction with an electrophile, the resulting sulfoxide is converted into a second magnesium reagent with iPrMgCl⋅LiCl (sulfoxide-magnesium exchange), which can be trapped with various electrophiles. Highly chemoselective TMPMgCl⋅LiCl and iPrMgCl⋅LiCl are compatible with a broad range of functional groups (e.g., F, Cl, CF(3) , CN, CO(2) tBu, alkynyl, ethers, thioethers). Large-scale reactions (25-40 mmol) and the preparation of fully functionalised furans and thiophenes are also reported., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A variety of unsaturated thioethers have been subjected to cross-coupling reactions with functionalized zinc reagents in the presence of a transition-metal catalyst. Three different catalytic systems based on Pd(OAc)(2) or [Ni(acac)(2)] and the ligands S-Phos or DPE-Phos gave the best results. N-Heterocyclic thioethers based on a pyridine, pyrimidine, pyrazine, pyridazine, triazine, benzothiazole, benzoxazole, pyrrole, or quinazoline ring, as well as thiomethylacetylenes, serve as electrophiles in this cross-coupling reaction. Aryl-, heteroaryl-, benzylic, and alkylzinc halides with sensitive functionalities, such as ester, nitrile, or ketone groups react at ambient temperature with unsaturated thioethers using a Ni catalyst. The corresponding Pd-catalyzed reactions require slightly higher temperatures. Large-scale cross-coupling experiments (10-20 mmol) with N-heterocycles are also reported., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Sample handling and storage conditions in specimens frozen over long periods of time can severely impact marker levels. If laboratory technologies, practices and related protocols change over time, biomarker studies are potentially biased and report erroneous results. These issues and pitfalls are often overlooked in system biology studies using previously collected and stored materials, and are likely to be one notable cause for biomarker candidates failing to be validated. We present results from simulation studies quantifying the loss in statistical power to detect true biomarkers, due to diminishing concentration of analytes in samples subject to poor handling and storage conditions.

This article provides an example of how Perinatal Periods of Risk (PPOR) can provide a framework and offer analytic methods that move communities to productive action to address infant mortality. Between 1999 and 2002, the infant mortality rate in the Antelope Valley region of Los Angeles County increased from 5.0 to 10.6 per 1,000 live births. Of particular concern, infant mortality among African Americans in the Antelope Valley rose from 11.0 per 1,000 live births (7 cases) in 1999 to 32.7 per 1,000 live births (27 cases) in 2002. In response, the Los Angeles County Department of Public Health, Maternal, Child, and Adolescent Health Programs partnered with a community task force to develop an action plan to address the issue. Three stages of the PPOR approach were used: (1) Assuring Readiness; (2) Data and Assessment, which included: (a) Using 2002 vital records to identify areas with the highest excess rates of feto-infant mortality (Phase 1 PPOR), and (b) Implementing Infant Mortality Review (IMR) and the Los Angeles Mommy and Baby (LAMB) Project, a population-based study to identify potential factors associated with adverse birth outcomes. (Phase 2 PPOR); and (3) Strategy and Planning, to develop strategic actions for targeted prevention. A description of stakeholders' commitments to improve birth outcomes and monitor infant mortality is also given. The Antelope Valley community was engaged and ready to investigate the local rise in infant mortality. Phase 1 PPOR analysis identified Maternal Health/Prematurity and Infant Health as the most important periods of risk for further investigation and potential intervention. During the Phase 2 PPOR analyses, IMR found a significant proportion of mothers with previous fetal loss (45%) or low birth weight/preterm (LBW/PT) birth, late prenatal care (39%), maternal infections (47%), and infant safety issues (21%). After adjusting for potential confounders (maternal age, race, education level, and marital status), the LAMB case-control study (279 controls, 87 cases) identified additional factors associated with LBW births: high blood pressure before and during pregnancy, pregnancy weight gain falling outside of the recommended range, smoking during pregnancy, and feeling unhappy during pregnancy. PT birth was significantly associated with having a previous LBW/PT birth, not taking multivitamins before pregnancy, and feeling unhappy during pregnancy. In response to these findings, community stakeholders gathered to develop strategic actions for targeted prevention to address infant mortality. Subsequently, key funders infused resources into the community, resulting in expanded case management of high-risk women, increased family planning services and local resources, better training for nurses, and public health initiatives to increase awareness of infant safety. Community readiness, mobilization, and alignment in addressing a public health concern in Los Angeles County enabled the integration of PPOR analytic methods into the established IMR structure and [the design and implementation of a population-based l study (LAMB)] to monitor the factors associated with adverse birth outcomes. PPOR proved an effective approach for identifying risk and social factors of greatest concern, the magnitude of the problem, and mobilizing community action to improve infant mortality in the Antelope Valley.

A variety of thiomethyl-substituted N-heterocycles such as pyridines, isoquinolines, pyrimidines, pyrazines, pyridazines, quinazolines, triazines, benzothiazoles, or benzoxazoles undergo smooth Ni-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, alkyl-, and benzylic zinc reagents using an inexpensive Ni(acac)(2)/DPE-Phos catalytic system at 25 degrees C.

The application of geographic information systems (GIS) technology to malaria surveillance presents an opportunity for focusing intervention and prevention activities in the areas most affected. We used GIS technology to map the prevalence of malaria in the Wosera Health and Demographic Surveillance Site, East Sepik Province, Papua New Guinea (PNG). Malaria, demographic and GIS data collected between 2001 and 2003 were aggregated and analysed. This was achieved by geo-coding or linking the prevalence and demographic data to the village location. All GIS manipulation and cartographic displays were performed in MapInfo. The results suggest that malaria is endemic with high prevalence as observed across the 3 surveyed years. The optimized implementation of GIS can be of tremendous benefit in the fight against malaria and other public health challenges in PNG.

Objective: To examine whether individual, condition-related, and system-related characteristics are associated with state performance (high, medium, low) on the provision of transition services to children with special health care needs (CSHCN)., Methods: We conducted descriptive, bivariate, and multivariable analyses of 16876 children aged 12 to 17 years by using data from the 2005-2006 National Survey of Children With Special Health Care Needs. Polytomous logistic regression was used to compare the characteristics of CSHCN residing within high-, medium-, and low-performance states, with low-performance states serving as the reference group., Results: Compared with non-Hispanic white CSHCN, Hispanic (adjusted odds ratio [aOR]: 0.25 [95% confidence interval (CI): 0.17-0.37]) and non-Hispanic black (aOR: 0.44 [95% CI: 0.30-0.62]) CSHCN were less likely to reside in a high-performance than in a low-performance state. Compared with CSHCN who had a medical home or adequate insurance coverage, CSHCN who did not have a medical home or adequate insurance coverage were less likely to reside in a high-performance than in a low-performance state (aOR: 0.73 [95% CI: 0.57-0.95]; aOR: 0.73 [95% CI: 0.58-0.93], respectively)., Conclusions: Key factors found to be important in a state's performance on provision of transition services to CSHCN were race/ethnicity and having a medical home and adequate insurance coverage. Efforts to support the Maternal and Child Health Bureau's integration of system-level factors in quality-improvement activities, particularly establishing a medical home and attaining and maintaining adequate insurance, are likely to help states improve their performance on provision of transition services.

Various thiomethyl-substituted N-heterocycles (pyridines, pyrimidines, pyrazines, pyridazines, triazines, benzothiazoles, benzoxazoles, pyrazoles, benzindazoles, quinazolines, etc.) undergo smooth Pd-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, benzylic-, and alkylzinc reagents using Pd(OAc)(2)/S-Phos as the catalytic system mostly at 25 degrees C. No copper salt is required to perform these reactions.

The use of TMPMgCl.LiCl and iPrMgCl.LiCl allows a sequential 2,3-difunctionalization of various 2-arylsulfinyl furans, thiophenes and benzofurans. Subsequent use of the same reagents permits a selective full functionalization of all 4 positions of the furan and thiophene scaffolds.

Context: Identifying how maternal residential location affects late initiation of prenatal care is important for policy planning and allocation of resources for intervention., Purpose: To determine how rural residence and other social and demographic characteristics affect late initiation of prenatal care, and how residence status is associated with self-reported barriers to accessing early prenatal care., Methods: This observational study used data from the 2003 Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) (N = 1,508), with late initiation of prenatal care (after the first trimester) as the primary outcome. We used Rural-Urban Commuting Area (RUCA) codes to categorize maternal residence as urban, large rural, or small/isolated rural. Multivariate logistic regression was used to evaluate whether category of residence was associated with late initiation of prenatal care after adjusting for other maternal factors. Association between categories of barriers to prenatal care and maternal category of residence were determined using the Cochran-Mantel-Haenszel test of association., Findings: We found no significant association between residence category and late initiation of prenatal care, or residence category and barriers to prenatal care initiation. Urban women tended to be over age 34 or nonwhite. Women from large rural areas were more likely to be younger than 18 years, unmarried, and have an unintended pregnancy. Women from small rural areas were more likely to use tobacco during pregnancy., Conclusions: Maternal residence category is not associated with late initiation of prenatal care or with barriers to initiation of prenatal care. Differences in maternal risk profiles by location suggest possible new foci for programs, such as tobacco education in small rural areas.

The aryl sulfoxide moiety (ArSO) allows an expedient two-step meta-, para-difunctionalization of readily available diaryl sulfoxides. In the first step, the sulfoxide plays the role of a directing metalation group. In the second step, triggered by i-PrMgCl x LiCl, it becomes a leaving group and undergoes a regioselective sulfoxide-magnesium exchange.

A direct room-temperature Ni-catalyzed cross-coupling of aminoalkylzinc halides, readily available from the corresponding aminoalkyl chlorides via Grignard reagents, with aryl and hetaryl electrophiles, allows a convenient one-step preparation of aminoalkyl (het)arenes, bearing a basic tertiary nitrogen in the side chain, including piperidine and tropane derivatives. Such aminoalkylarene scaffolds are widely present in various biologically active molecules.

Objective: Early warning scoring systems are widely used in clinical practice to allow early recognition of the deteriorating patient, but they lack validation. We aimed to test the ability of physiologic variables, either alone or in existing early scoring systems, to predict major deterioration in a patient's condition and attempt to derive functions with superior accuracy., Design: A comparative cohort study., Setting: A teaching hospital in Scotland., Patients: Two cohorts of general surgical high-dependency patients. The cohorts are a group of surgical high-dependency care patients who did not require intensive care admission and another group of patients who did require admission., Interventions: None., Measurements and Main Results: Prospective physiologic data on consecutive surgical high-dependency unit patients were collected and compared with physiologic data on patients admitted to the intensive care unit from the same surgical high-dependency units. Data were quality checked and summarized, and discriminant analysis and receiver operator curves were used to discriminate between the groups. There were significant physiologic differences between groups with regard to heart rate (p<.001, area under the receiver operating characteristic curve [AUC] 0.7), respiratory rate (p<.001, AUC 0.71), and oxygen saturation (p<.001, AUC 0.78) across time points. This was not present for systolic blood pressure or temperature. Existing early warning scoring systems had good discriminatory power (AUC 0.83-0.86). We derived discriminant functions, which have a high predictive ability to determine differences between groups (p<.0001, AUC 0.86-0.90). We found that heart rate and respiratory rate could detect differences between groups at 6 and 8 hrs before ICU admission, but oxygen saturation and the discriminant function 2 could detect differences 48 hrs before ICU admission., Conclusions: Some commonly used physiologic variables have reasonable power in determining the difference between patients requiring intensive care unit admission, but others are poor. Existing early warning scores have comparatively good discriminatory power. We have derived functions with excellent predictive power in this derivation cohort.

Melanoma is one of the most devastating malignancies with a rising incidence and lack of effective treatments for advanced disease. Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and altered expression of alpha(v)beta(3) integrin are critical for melanoma development and progression. Ras-associated protein-1 (Rap1), a Ras family member of the small GTPases, has emerged as a key mediator in these two important processes. In this study, we have shown Rap1 activation in cells derived from two human metastatic melanomas and also in three of seven cutaneous metastatic melanoma tissues. We found increased extracellular signal-regulated kinase (ERK) activity in the tumors with detected Rap1 activity that interestingly harbored neither BRAF nor N-Ras mutation, suggesting a role for Rap1 in ERK activation in vivo. We also showed Rap1 and ERK activation by both hepatocyte growth factor (HGF) and 8CPT-2Me-cAMP (an activator of Epac, a Rap1 guanine nucleotide exchange factor) in two human melanoma cell lines. In addition, the activation of ERK by HGF was reduced, at least in part, by small interfering RNAs against Rap1 and a dominant-negative Rap1. Finally, a functional role for Rap1 activation was shown by Rap1-induced alpha(v)beta(3) integrin activation and consequent increased melanoma cell migration in vitro. Taken together, these results show that Rap1 is involved in the activation of MAPK pathway and integrin activation in human melanoma and suggest a potential role for Rap1 in melanoma tumorigenesis and metastasis.

Objectives: To comparatively assess the irritation and sensitisation of the Estradot transdermal oestrogen patch, in healthy postmenopausal women, using the Menorest transdermal oestrogen patch, as a comparator., Methods: In an open-label, single-centre, randomised, active-treatment, within-patient controlled study, 208 healthy postmenopausal women, age range 40-70 years, received and completed simultaneous treatment with a 5 cm(2) (50 microg/day) oestradiol patch (Estradot) and a 14.5 cm(2) (50 microg/day) oestradiol patch (Menorest). The treatment was given for 72 h, then 96 h, for eight successive applications during an induction phase, and for 72 h during a challenge phase. There was a 14-day resting period between phases. Skin irritation (measured by erythema on a scale of 0-4), topical sensitisation, patch adherence and local skin reaction, were assessed and recorded immediately before or after removal of each patch, as appropriate., Results: Most patients experienced a significant difference in irritation with Menorest than with Estradot (P < 0.0001) at the end of the induction phase. Patch loss was also significantly higher for Menorest as compared to Estradot (P = 0.0253) at the end of the induction phase. Most incidences of erythema were classified as slight (score of 1), and there was no significant difference in the percentage of topical sensitisation, or in the incidence of local skin reactions between Estradot and Menorest. Patch loss was low for both systems., Conclusions: Estradot demonstrates reduced skin irritation, superior adhesion and a lower rate of patch loss compared to Menorest., (Copyright 2002 Published by Elsevier Science Ireland Ltd.)

Background: Although cyclosporine (CsA) has been a mainstay in liver transplantation immunosuppression the original formulation [Sandimmune (SIM)] has variable absorption, particularly in children. Neoral is a new formulation of CsA that may have improved biovailability that would be advantageous in children. This study was undertaken to assess the pharmacokinetics (PK) and effects on outcome of Neoral versus Sandimmune (SIM) in primary pediatric liver transplant recipients., Methods: Thirty-two patients were randomized to receive Neoral (17 patients) or SIM (15 patients) in the early posttransplant period (days 1-7) in a double-blind fashion. Intravenous CsA was instituted immediately posttransplant followed by Neoral or SIM as soon as the patient was tolerating oral fluids (days 1-7). PK were compared after the first dose (1-7 days), 3 weeks, and 6 and 12 months posttransplant. In addition, side effects, effect of age and food on absorption, and rejection episodes were assessed by intent to treat analysis. Notable characteristics of this study include the use of a central laboratory for all sample analyses and the assessment of renal function using radioisotopic evaluation of glomerular filtration rates., Results: At baseline the two groups were comparable. Neoral resulted in higher peak levels of CsA and total drug exposure with comparable time to peak drug levels at days 1-7 and week 3. This trend was maintained at 6 and 12 months. Time on i.v. CsA was reduced in the Neoral group (8.4 vs. 11.1 days) and the weight adjusted daily dose of SIM required to achieve target trough levels was about 2-fold more than Neoral from day 22 onward. In addition, biopsy proven and treated and steroid-resistant rejection episodes were fewer in the Neoral group (6 vs. 12; P=0.01 and 1 vs. 8: P=0.004, respectively). Side effects were comparable in both treatment groups., Conclusions: Neoral was well tolerated and had greater biovailability than SIM without any increase in the incidence of side effects. In addition fewer episodes of rejection were observed with Neoral versus SIM. We conclude that Neoral is the CsA formulation of choice for use in pediatric liver transplant recipients.

Gender and kinship were examined with regard to caregivers' use of informal and formal support and to two models of support (substitution or supplementation). Three groups of caregivers of a demented relative living at home--husbands, wives, and adult daughters--were compared on measures of both informal and formal support. The gender hypothesis deals with the similarities among caregivers of the same gender with respect to support. The kinship hypothesis refers to the similarities among caregivers having the same kinship with the carereceiver. The gender hypothesis was confirmed for informal informational support while the kinship hypothesis was supported for informal conflictual support. For most of the comparisons, the three groups of caregivers shared more similarities than differences. The interchangeability between informal and formal support seems to fall under the perspective of kinship because the daughter group is the only one where a model of supplementation was observed.

At the Ottawa Civic Hospital hemodialysis unit, our prescribed blood flow rate for temporary indwelling catheters runs at 200 mls/min. We were concerned that, with the reversal of the ports of these catheters, our patients were not receiving the dialysis prescription ordered for them due to decreased efficiency of their treatment. Twenty-five of 108 patients in the program were included in a study related to the percentage of access recirculation when ports were reversed or not reversed. Of those 25 patients, approximately 42% had their ports reversed. The study took place over a two-week period and involved approximately six dialysis sessions per patient. Results indicated that the percentage recirculation increased from 2.3%-4.1% when ports were connected normally, to 12% when ports were reversed. As a result, a policy is now in place whereby our patients' treatment time is increased 20 minutes for reversed ports. In summary, recirculation rate increased with reversal of ports in temporary indwelling catheters. Extension of prescribed treatment times when ports are reversed will maintain the efficiency of dialysis.

The effect of a topically administered alpha-adrenoceptor agonist (phenylpropanolamine) after allergen challenge was evaluated in a placebo-controlled double-blind crossover study in 10 subjects with allergic rhinitis in an asymptomatic period. The nasal airway resistance was objectively measured by anterior rhinomanometry after nasal allergen challenge. The degree of nasal blockage, secretion and the number of sneezes were registered in a score. Nasal airway resistance and the degree of blockage were found to be significantly reduced. Thus, alpha-adrenoceptor agonists might be used topically for symptomatic treatment of allergic rhinitis comprising mucosal congestion.

The aim of the present investigation was to determine to what extent beta-lactamase producing Haemophilus influenzae (H.i.) and Branhamella catarrhalis (B.c.) were isolated in cases of failure of treatment of acute otitis media (AOM) with phenoxymethylpenicillin. Among children with suspected therapeutic failure referred to an ENT specialist altogether 11, 15% of those referred, fulfilled the criteria of AOM. Three of them were on erythromycin, 1 on ampicillin and 7 on phenoxymethylpenicillin. In 5 of the children treated with phenoxymethylpenicillin H.i. was isolated from middle ear exudate and/or the nasopharynx. All H.i. isolates were non-capsulated and beta-lactamase negative. One beta-lactamase producing B.c. was isolated from the nasopharynx in a patient with pure culture of H.i. in the ear exudate. The present investigation did not support the suggestion that beta-lactamase producing H.i. or B.c. are major causative agents in therapeutic failures of AOM treated with phenoxymethylpenicillin and did not produce any evidence supporting a change from the recommended ampicillin esters/amoxycillin in therapeutic failures.