Audit report on the City of Strawberry Point, Iowa for the year ended June 30, 2006

Audit report on the City of Strawberry Point, Iowa for the year ended June 30, 2006

Determination of oseltamivir and oseltamivir carboxylate in human plasma by liquid chromatography-tandem mass spectrometry

Introduction: Oseltamivir phosphate (OP), the prodrug of oseltamivir carboxylate (OC; active metabolite), is marketed since 10 years for the treatment of seasonal influenza flu. It has recently received renewed attention because of the threat of avian flu H5N1 in 2006-7 and the 2009-10 A/H1N1 pandemic. However, relatively few studies have been published on OP and OC clinical pharmacokinetics. The disposition of OC and the dosage adaptation of OP in specific populations, such as young children or patients undergoing extrarenal epuration, have also received poor attention. An analytical method was thus developed to assess OP and OC plasma concentrations in patients receiving OP and presenting with comorbidities or requiring intensive care. Methods: A high performance liquid chromatography coupled to tandem mass spectrometry method (HPLC-MS/MS) requiring 100-µL aliquot of plasma for quantification within 6 min of OP and OC was developed. A combination of protein precipitation with acetonitrile, followed by dilution of supernant in suitable buffered solvent was used as an extraction procedure. After reverse phase chromatographic separation, quantification was performed by electro-spray ionization-triple quadrupole mass spectrometry. Deuterated isotopic compounds of OP and OC were used as internal standards. Results: The method is sensitive (lower limit of quantification: 5 ng/mL for OP and OC), accurate (intra-/inter-assay bias for OP and OC: 8.5%/5.5% and 3.7/0.7%, respectively) and precise (intra-/inter-assay CV%: 5.2%/6.5% and 6.3%/9.2%, respectively) over the clinically relevant concentration range (upper limits of quantification 5000 ng/mL). Of importance, OP, as in other previous reports, was found not to be stable ex vivo in plasma on standard anticoagulants (i.e. EDTA, heparin or citrate). This poor stability of OP has been prevented by collecting blood samples on commercial fluoride/oxalate tubes. Conclusions: This new simple, rapid and robust HPLC-MS/MS assay for quantification of OP and OC plasma concentrations offers an efficient tool for concentration monitoring of OC. Its exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics (e.g. renal clearance). The usefulness of systematic therapeutic drug monitoring in patients appears therefore questionable. However, pharmacokinetic studies are still needed to extend knowledge to particular subgroups of patients or dosage regimens.

The association between body mass index and patients' experiences with inpatient care.

OBJECTIVE: To explore the association between patients' body mass index (BMI) and their experiences with inpatient care. DESIGN: Cross-sectional. Mail survey. SETTING: University Hospital of Geneva. PARTICIPANTS: Questionnaires were mailed to 2385 eligible adult patients, 6 weeks after discharge (response rate = 69%). MAIN OUTCOME MEASURES: Patients' experiences with care were measured using the Picker inpatient survey questionnaire. BMI was calculated using self-reported height and weight. Main dependent variables were the global Picker patient experience (PPE-15) score and nine dimension-specific problem scores, scored from 0 (no reported problems) to 1 (all items coded as problems). We used linear regressions, adjusting for age, gender, education, subjective health, smoking and hospitalization, to assess the association between patients' BMI and their experiences with inpatient care. RESULTS: Of the patients, 4.8% were underweight, 50.8% had normal weight, 30.3% were overweight and 14.1% were obese. Adjusted analysis shows that compared with normal weight, obesity was significantly associated with fewer problematic items in the surgery-related information domain, and being underweight or overweight was associated with more problematic items in the involvement of family/friends domain. The global PPE-15 score was significantly higher (more problems) for underweight patients. CONCLUSIONS: Underweight patients, but not obese patients, reported more problems during hospitalization.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Changes in spring-mass model characteristics during repeated running sprints.

This study investigated fatigue-induced changes in spring-mass model characteristics during repeated running sprints. Sixteen active subjects performed 12 × 40 m sprints interspersed with 30 s of passive recovery. Vertical and anterior-posterior ground reaction forces were measured at 5-10 m and 30-35 m and used to determine spring-mass model characteristics. Contact (P &lt; 0.001), flight (P &lt; 0.05) and swing times (P &lt; 0.001) together with braking, push-off and total stride durations (P &lt; 0.001) lengthened across repetitions. Stride frequency (P &lt; 0.001) and push-off forces (P &lt; 0.05) decreased with fatigue, whereas stride length (P = 0.06), braking (P = 0.08) and peak vertical forces (P = 0.17) changes approached significance. Center of mass vertical displacement (P &lt; 0.001) but not leg compression (P &gt; 0.05) increased with time. As a result, vertical stiffness decreased (P &lt; 0.001) from the first to the last repetition, whereas leg stiffness changes across sprint trials were not significant (P &gt; 0.05). Changes in vertical stiffness were correlated (r &gt; 0.7; P &lt; 0.001) with changes in stride frequency. When compared to 5-10 m, most of ground reaction force-related parameters were higher (P &lt; 0.05) at 30-35 m, whereas contact time, stride frequency, vertical and leg stiffness were lower (P &lt; 0.05). Vertical stiffness deteriorates when 40 m run-based sprints are repeated, which alters impact parameters. Maintaining faster stride frequencies through retaining higher vertical stiffness is a prerequisite to improve performance during repeated sprinting.

The In Vitro Mass-Produced Model Mycorrhizal Fungus, Rhizophagus irregularis, Significantly Increases Yields of the Globally Important Food Security Crop Cassava.

The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate (P). The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future.

Audit report on the City of Center Point, Iowa for the year ended June 30, 2007

Audit report on the City of Center Point, Iowa for the year ended June 30, 2007

Audit report on the City of Strawberry Point, Iowa for the year ended June 30, 2007

Audit report on the City of Strawberry Point, Iowa for the year ended June 30, 2007