Performance comparison of Yb:YAG ceramics and crystal gain material in a large-area, high-energy, high average-power diode-pumped laser.

We compare for the first time the influence of different Yb:YAG gain media on the performance of a large-area, high average-power laser system with an output energy of up to 6 J. Monocrystalline slabs grown by a new technique without central growth defect are compared with ceramics. Small signal gain, maximum output energy and thermal lensing are compared for ceramic slabs with co-sintered amplified spontaneous emission (ASE) absorber cladding, monocrystalline slab with and without optically bonded ASE absorber cladding, and surface structured monocrystalline slabs. We show that these large monocrystals with optically bonded absorber cladding have similar performance to cladded ceramics, so far the only material for high-energy Yb:YAG lasers.

High-energy, ceramic-disk Yb:LuAG laser amplifier.

We report the first short-pulse amplification results to several hundred millijoule energies in ceramic Yb:LuAG. We have demonstrated ns-pulse output from a diode-pumped Yb:LuAG amplifier at a maximum energy of 580 mJ and a peak optical-to-optical efficiency of 28% at 550 mJ. In cavity dumped operation of a nanosecond oscillator we obtained 1 mJ at up to 100 Hz repetition rate. A gain bandwidth of 5.4 nm was achieved at room temperature by measuring the small-signal single-pass gain. Furthermore, we compared our results with Yb:YAG within the same amplifier system.

Combined sewer overflows: an environmental source of hormones and wastewater micropollutants.

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40-90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency.

Optimising the efficiency of pulsed diode pumped Yb:YAG laser amplifiers for ns pulse generation.

We present a numerical model of a pulsed, diode-pumped Yb:YAG laser amplifier for the generation of high energy ns-pulses. This model is used to explore how optical-to-optical efficiency depends on factors such as pump duration, pump spectrum, pump intensity, doping concentration, and operating temperature. We put special emphasis on finding ways to achieve high efficiency within the practical limitations imposed by real-world laser systems, such as limited pump brightness and limited damage fluence. We show that a particularly advantageous way of improving efficiency within those constraints is operation at cryogenic temperature. Based on the numerical findings we present a concept for a scalable amplifier based on an end-pumped, cryogenic, gas-cooled multi-slab architecture.

The effect of temperature and humidity on the permeability of film dressings.

The moisture vapour permeability of a dressing can make an important contribution to its overall fluid handling capacity. Despite the fact that this parameter is often quoted in scientific literature and manufacturers' promotional material, it is a concept that is not generally well understood. In particular, the effect of changing environmental conditions upon experimentally determined permeability values for particular dressings is rarely acknowledged. The present study was undertaken to derive and validate a method that could be used to predict the permeability of a self-adhesive semipermeable film dressing under specific conditions of temperature and humidity using a single set of data generated in the laboratory. A calculator that facilitates this process is also described.

Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force generation during systole.

We tested the hypothesis that intracellular Ca++ [( Ca++]i) overload underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy. Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease. The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and [Ca++]i was measured with the bioluminescent calcium indicator aequorin. In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components. At 38 degrees C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared develop, which produced a rise in end-diastolic [Ca++]i, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development. We also found that drugs with increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them. These results may explain why patients with hypertrophic cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophic cardiomyopathy.

HPLC-NMR with severe column overloading: fast-track metabolite identification in urine and bile samples from rat and dog treated with [14C]-ZD6126.

The subject of this study was the determination of the major urinary and biliary metabolites of [(14)C]-ZD6126 following i.v. administration to female and male bile duct cannulated rats at 10 mg/kg and 20 mg/kg, respectively, and male bile duct cannulated dogs at 6 mg/kg by HPLC-NMR spectroscopy. ZD6126 is a phosphorylated pro-drug, which is rapidly hydrolysed to the active metabolite, ZD6126 phenol. The results presented here demonstrate that [(14)C]-ZD6126 phenol is subsequently metabolised extensively by male dogs and both, male and female rats. Recovery of the dose in bile and urine was determined utilising the radiolabel, revealing biliary excretion as the major route of excretion (93%) in dog, with the majority of the radioactivity recovered in both biofluids in the first 6 h. In the rat, greater than 92% recovery was obtained within the first 24 h. The major route of excretion was via the bile 51-93% within the first 12 h. The administered phosphorylated pro-drug was not observed in any of the excreta samples. Metabolite profiles of bile and urine samples were determined by high performance liquid chromatography with radiochemical detection (HPLC-RAD), which revealed a number of radiolabelled components in each of the biofluids. The individual metabolites were subsequently identified by HPLC-NMR spectroscopy and HPLC-MS. In the male dog, the major component in urine and bile was the [(14)C]-ZD6126 phenol glucuronide, which accounted for 3% and 77% of the dose, respectively. [(14)C]-ZD6126 phenol was observed in urine at 1% of dose, but was not observed in bile. A sulphate conjugate of demethylated [(14)C]-ZD6126 phenol was identified in bile by HPLC-NMR and confirmed by HPLC-MS. In the rat, the bile contained two major radiolabelled components. One was identified as the [(14)C]-ZD6126 phenol glucuronide, the other as a glucuronide conjugate of demethylated [(14)C]-ZD6126 phenol. However, a marked difference in the proportions of these two components was observed between male and female rats, either due to a sex difference in metabolism or a difference in dose level. The glucuronide conjugate of the demethylated [(14)C]-ZD6126 phenol was present at higher concentration in the bile of male rats (4-34%), while the phenol glucuronide was present at higher concentration in the bile of female rats (8-70%) over a 0-6 h collection period. A third component was only observed in the bile samples (0-6 h and 6-12 h) of male rats. This was identified as being the same sulphate conjugate of demethylated [(14)C]-ZD6126 phenol as the one observed in dog bile. The rat urines contained two main metabolites in greatly varying concentrations, namely the demethylated [(14)C]-ZD6126 phenol glucuronide and the glucuronide of [(14)C]-ZD6126 phenol. Again, the differences in relative amounts between male and female rats were observed, the major metabolite in the urines from male rats being the demethylated [(14)C]-ZD6126 phenol (0-17% in 0-24 h), whilst the phenol glucuronide, accounting for 0.5-50% of the dose over 0-24 h, was the major metabolite in females. Methanolic extracts of the pooled biofluid samples were submitted for HPLC-NMR for the quick identification of the major metabolites. Following a single injection of the equivalent of 6-28 ml of the biofluids directly onto the HPLC-column with minimal sample preparation, the metabolites could be largely successfully isolated. Despite severe column overloading, the major metabolites of [(14)C]-ZD6126 could be positively identified, and the results are presented in this paper.

The increasing prevalence of diabetes in South Australia: the relationship with population ageing and obesity.

OBJECTIVES: To use representative population surveillance data to monitor and project changes in the prevalence of diabetes for different age and body mass index (BMI) groups. STUDY DESIGN: Representative, annual, face-to-face South Australian Health Omnibus Surveys, 1991-2003 (n=3000 per year). METHODS: Trends in self-reported diabetes prevalence by age group and BMI were examined. Separate projections were made on the basis of predicted changes in population demography and diabetes prevalence. RESULTS: The age-sex standardized absolute prevalence of self-reported diabetes among people aged 15 years and over increased from 3.5% in 1991 to 6.7% in 2003. If this current trend continues, the prevalence is expected to increase to 10.5% by 2016. The prevalence of diabetes was significantly higher among those classified as obese (6.5% in 1991 to 12.2% in 2003) than those with normal BMI. The greatest relative percentage increase in prevalence between 1991 and 2003 (169%) was seen among people aged 15-39 years. Taking both age group and BMI classification into account, the greatest relative percentage increases over this time were seen among those with normal BMI aged 60 years or older (148%), and those who were obese and aged less than 60 years (139%). CONCLUSIONS: The prevalence of diabetes and obesity increased significantly between 1991 and 2003. Population ageing and an increase in diabetes prevalence in the future will further increase the burden of diabetes. Future increases in diabetes prevalence are not inevitable, however, if investments are made in public health prevention programmes, particularly those addressing obesity.

Variability of urinary albumin excretion in patients with microalbuminuria.

OBJECTIVE: To estimate the within-person variability (SDi) for the overnight urinary albumin excretion rate (AER) in diabetic patients with persistent microalbuminuria. RESEARCH DESIGN AND METHODS: Thirteen normotensive diabetic patients in stable medical control, with normal renal function and without any associated cardiovascular or other clinical disorders, collected overnight urines at monthly intervals during one year. AER was determined by radioimmunoassay. RESULTS: Analysis of individual series of AER showed a significant trend (P < or = 0.01) in three cases. The remaining patients (eight men, two women; seven with insulin-dependent diabetes mellitus) had a median mean AER 102 micrograms/min (range 30-238 micrograms/min). Because the individual mean AERs were significantly associated with their respective SDis, the data was loge transformed. LogeSDi was estimated as 0.420, and its 90% probability range (0.353-0.490) was calculated using the bootstrap method. CONCLUSIONS: The high within-person variance for AER means that only people with an initial AER in the range of 53-76 micrograms/min have a high probability (P > or = 0.95) of being classified as microalbuminuric (20-200 micrograms/min) on a subsequent specimen. However, subjects with an initial AER > or = 53 or > or = 80 micrograms/min have a 95 and 99% probability of persistent microalbuminuria. The large variability of AER limits its potential as a serial marker to detect any gradual deterioration of established renal dysfunction.

Alternate site testing for HbA1c using the Primus CLC330 GHb analyzer.

OBJECTIVE: To determine whether the Primus high-pressure liquid chromatography (HPLC) is suited to alternate site testing (AST) for HbA1c in a hospital diabetes outpatient clinic. RESEARCH DESIGN AND METHODS: Patients were attending the clinic for routine management of their diabetes. A number of diabetic patients with uremia (n = 11) were also investigated. HbA1c levels were measured in the outpatient setting by the Primus HPLC and in a more limited study the DCA-2000 instrument using the new 6-min assay cartridge. HbA1c measurements were also performed with Pierce affinity minicolumns and a Bio-Rad Variant HPLC. RESULTS: The Primus HPLC assay had low imprecision of 2.3, 1.6, and 1.0% for HbA1c levels of 4.7, 7.3, and 11.1%, respectively, and was not prone to interference by carbamylated hemoglobin as found for the ion-exchange Variant HPLC method. Method comparison studies showed that the bias and proportional error between the Pierce affinity minicolumn procedure (standardized with respect to an external quality control program) and the Primus HPLC (Y) was -0.4 and 1.2% respectively (n = 32). Similarly the bias and proportional error between the Primus and DCA-2000 methods was 0.7 and -2.5%. The Primus was shown to give falsely elevated HbA1c concentrations if the time between sequential injections was > 28 min. CONCLUSIONS: The Primus HPLC has a decided advantage over specialty AST instruments, like the DCA-2000, in not only meeting AST requirements but also allowing rapid automated batch processing of all laboratory HbA1c samples.

Concentrations of hormones, pharmaceuticals and other micropollutants in groundwater affected by septic systems in New England and New York.

Septic-system discharges can be an important source of micropollutants (including pharmaceuticals and endocrine active compounds) to adjacent groundwater and surface water systems. Groundwater samples were collected from well networks tapping glacial till in New England (NE) and sandy surficial aquifer New York (NY) during one sampling round in 2011. The NE network assesses the effect of a single large septic system that receives discharge from an extended health care facility for the elderly. The NY network assesses the effect of many small septic systems used seasonally on a densely populated portion of Fire Island. The data collected from these two networks indicate that hydrogeologic and demographic factors affect micropollutant concentrations in these systems. The highest micropollutant concentrations from the NE network were present in samples collected from below the leach beds and in a well downgradient of the leach beds. Total concentrations for personal care/domestic use compounds, pharmaceutical compounds and plasticizer compounds generally ranged from 1 to over 20 µg/L in the NE network samples. High tris(2-butoxyethyl phosphate) plasticizer concentrations in wells beneath and downgradient of the leach beds (>20 µg/L) may reflect the presence of this compound in cleaning agents at the extended health-care facility. The highest micropollutant concentrations for the NY network were present in the shoreline wells and reflect groundwater that is most affected by septic system discharges. One of the shoreline wells had personal care/domestic use, pharmaceutical, and plasticizer concentrations ranging from 0.4 to 5.7 µg/L. Estradiol equivalency quotient concentrations were also highest in a shoreline well sample (3.1 ng/L). Most micropollutant concentrations increase with increasing specific conductance and total nitrogen concentrations for shoreline well samples. These findings suggest that septic systems serving institutional settings and densely populated areas in coastal settings may be locally important sources of micropollutants to adjacent aquifer and marine systems.

Familial corticosteroid-binding globulin deficiency due to a novel null mutation: association with fatigue and relative hypotension.

Corticosteroid-binding globulin is a 383-amino acid glycoprotein that serves a hormone transport role and may have functions related to the stress response and inflammation. We describe a 39-member Italian-Australian family with a novel complete loss of function (null) mutation of the corticosteroid-binding globulin gene. A second, previously described, mutation (Lyon) segregated independently in the same kindred. The novel exon 2 mutation led to a premature termination codon corresponding to residue -12 of the procorticosteroid-binding globulin molecule (c.121G-->A). Among 32 family members there were 3 null homozygotes, 19 null heterozygotes, 2 compound heterozygotes, 3 Lyon heterozygotes, and 5 individuals without corticosteroid-binding globulin mutations. Plasma immunoreactive corticosteroid-binding globulin was undetectable in null homozygotes, and mean corticosteroid-binding globulin levels were reduced by approximately 50% at 18.7 +/- 1.3 microg/ml (reference range, 30-52 microg/ml) in null heterozygotes. Morning total plasma cortisol levels were less than 1.8 microg/dl in homozygotes and were positively correlated to the plasma corticosteroid-binding globulin level in heterozygotes. Homozygotes and heterozygote null mutation subjects had a high prevalence of hypotension and fatigue. Among 19 adults with the null mutation, the systolic blood pressure z-score was 12.1 +/- 3.5; 11 of 19 subjects (54%) had a systolic blood pressure below the third percentile. The mean diastolic blood pressure z-score was 18.1 +/- 3.4; 8 of 19 subjects (42%) had a diastolic blood pressure z-score below 10. Idiopathic chronic fatigue was present in 12 of 14 adult null heterozygote subjects (86%) and in 2 of 3 null homozygotes. Five cases met the Centers for Disease Control criteria for chronic fatigue syndrome. Fatigue questionnaires revealed scores of 25.1 +/- 2.5 in 18 adults with the mutation vs. 4.2 +/- 1.5 in 23 healthy controls (P < 0.0001). Compound heterozygosity for both mutations resulted in plasma cortisol levels comparable to those in null homozygotes. Abnormal corticosteroid-binding globulin concentrations or binding affinity may lead to the misdiagnosis of isolated ACTH deficiency. The mechanism of the association between fatigue and relative hypotension is not established by these studies. As idiopathic fatigue disorders are associated with relatively low plasma cortisol, abnormalities of corticosteroid-binding globulin may be pathogenic.

Hypercalcemia associated with parenteral amino acid and dextrose infusion.

A patient receiving parenteral nutrition with an amino acid dextrose solution developed hypercalcemia which seemed related to the rate of nutrient infusion. In a retrospective study of patients receiving parenteral nutrition over a 3-month period six of 72 (8%) developed hypercalcemia. After changes in infusion rate there were corresponding changes in the serum calcium concentration. There was a significant correlation between the serum calcium concentration and the average infusion rate over the preceding four days (p = 0.012). This was even more significant (p less than 0.005) when ionized calcium was calculated to diminish the effects of calcium binding by proteins.

Urinary free corticosteroid excretion and renal function.

Theoretically urinary free corticosteroid excretion should be affected by renal function and this would make it a less sensitive index of hypercortisolaemia. In 28 consecutive urine samples there was a clear relationship (r = 0.83; P less than 0.001) over a range of creatinine clearances 0.3-200 ml/min. Although an allowance could be made for renal function this would not necessarily improve the discrimination of normal from abnormal. Until data comparing corrected to uncorrected urinary free corticosteroid excretion become available, we recommend a short dexamethasone test as the initial investigation in patients with suspected hypercortisolaemia and abnormal plasma creatinine concentrations.

Familial hypouricaemia associated with renal tubular uricosuria and uric acid calculi: case report.

We describe a patient with the rare combination of uric acid calculi, familial hypouricaemia, and increased renal urate clearance.

Alpha1-fetoprotein in the diagnosis of hepatoma: statistical and cost benefit aspects.

A rational comparison of different serum concentrations of alpha1-fetoprotein (S-AFP) in the diagnosis of hepatoma must be made. We took data on the sensitivity and specificity of different diagnostic S-AFP concentrations from the literature and evaluated them statistically and by Bayesian analysis. In our patients (hepatoma prevalence 0.028) a sensitive diagnostic concentration (30-50 ng/ml) will misdiagnose hepatoma so often that a positive test will indicate hepatoma in only 10% of cases. A positive test at a specific diagnostic concentration (500 ng/ml) indicates hepatoma in 100% of cases and is preferable in terms of cost benefit. Although the lower concentration will diagnose a larger proportion of patients with hepatoma (74% compared with 59%) the 'costs' of excluding false positives are considerable (A$2545 per extra case with 2.5% of patients suffering significant morbidity). In western societies, where the prevalence of hepatoma is low, a higher, less sensitive but more specific diagnostic S-AFP concentration is appropriate.

c-fos expression in the paraventricular nucleus of the hypothalamus following intracerebroventricular infusions of neuropeptide Y.

Intracerebroventricular (i.c.v.) infusions of neuropeptide Y (NPY) (2500 pmol) induced c-fos protein in the paraventricular nucleus (PVN) of intact male rats 60 min later. The greatest expression was observed in the dorsal (parvicellular) region of the PVN; there were intermediate levels in the lateral (magnocellular) and lowest ones in the medial (parvicellular) regions. Allowing rats to eat during the post-infusion interval did not modify this pattern of c-fos expression. Depriving rats of food for either 24 or 48 h did not induce recognisable expression of c-fos in the PVN, and allowing 24 h-deprived rats to eat also had no effect on PVN c-fos. Plasma insulin was increased by i.c.v. NPY, and raised still further in rats that were allowed to eat following NPY infusions. However, plasma glucose was not altered by either treatment. Food-deprived rats had low levels of insulin, but unaltered blood glucose, compared to controls. These results show that NPY can induce c-fos expression in both parvicellular and magnocellular areas of the PVN. The pattern of expression within the PVN seems to differ from that induced by other peptides, such as angiotensin II, vasopressin and corticotropin-releasing factor, suggesting that distinct populations of neurons are activated by different peptides within the complex structure of the PVN. Food deprivation does not induce c-fos expression within the PVN, though other studies have shown that NPY levels and release are both increased, so there is no simple relation between current energy state, blood levels of either glucose or insulin and c-fos expression within the PVN.

Dietary compliance in the short bowel syndrome.

Psychologic problems associated with the short bowel syndrome have received limited recognition. The literature has previously considered these problems as due to the underlying condition or its treatment. We present a case illustrating these as well as addressing the problem of compliance to treatment that has been previously neglected. The occurrence of metabolic acidosis in this patient whenever there was not strict dietary adherence to diet provide a ready marker to her noncompliance.

Feasibility study for a two-dimensional diagnostic ultrasound velocity mapping system.

A receive beam-tracking technique is introduced for simultaneously measuring more than one dimension of an existing velocity vector in medical ultrasound. By using flexible beamforming and a conventional linear-array transducer, vectors can be measured at real-time frame rates over a significant field of view. Both simulations and in vitro experiments show that this technique should provide more accurate measurements of blood flow velocities in the human body than is available with current color flow mapping systems.