Tuning the stability of bimetallic Ce(iv)/Zr(iv)-based MOFs with UiO-66 and MOF-808 structures.

A series of solid solutions of bimetallic Ce/Zr-UiO-66 and -MOF-808 compounds with a varying ratio of Ce4+ to Zr4+ were obtained under mild reaction conditions within 15 min. The lattice parameters of the mixed-metal compounds are in accordance with Vegard's law. Samples with Ce ≤20 at% exhibit an enhanced thermal stability, better resistance against acids and smaller particle sizes.

Synthesis and structure of Zr(iv)- and Ce(iv)-based CAU-24 with 1,2,4,5-tetrakis(4-carboxyphenyl)benzene.

Two new MOFs denoted as M-CAU-24 (M = Zr, Ce) based on 1,2,4,5-tetrakis(4-carboxyphenyl)benzene (H4TCPB) were obtained under mild reaction conditions within 15 min. The MOFs with composition [M6(µ3-O)4(µ3-OH)4(OH)4(H2O)4(TCPB)2] crystallise in the scu topology, a connectivity hitherto unreported for Zr-MOFs with tetracarboxylate linker molecules. Zr-CAU-24 exhibits UV/blue ligand-based luminescence.

Evaluating the cost-effectiveness of reduced mild hypoglycaemia in subjects with Type 1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden, Finland and the Netherlands.

AIMS: To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. METHODS: A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€). RESULTS: Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12,644 (Denmark), € 12,612 (Sweden), € 16,568 (Finland) and € 12,216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin. CONCLUSIONS: Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings.

Willingness to pay for health improvements associated with anti-diabetes treatments for people with type 2 diabetes.

OBJECTIVES: This study aimed to investigate the most important consequences of diabetes medication, as measured by the patients' willingness to pay (WTP). RESEARCH DESIGN AND METHODS: People in Sweden were recruited using existing nationwide e-mail panels if they were adults (>or=18 years) with type 2 diabetes and were receiving pharmacological anti-diabetes treatment(s). Data were collected electronically and results were analysed using a standard statistical model designed for choice games (conditional logit). Six characteristics relating to treatment of diabetes were examined: weight (gain or loss), mean glycated haemoglobin level (HbA(1c)), hypoglycaemic events, nausea, need for injections (with or independently of meals), and blood glucose testing. RESULTS: A total of 461 people with type 2 diabetes (291 males; 170 females) completed an internet questionnaire and were eligible for inclusion. Participants placed high value on weight loss and nausea avoidance; they would pay 176 Swedish Krona (SEK)/euro15.61 per month to lose 1 kg, and would pay SEK 560 (euro49.67) per month to avoid nausea completely. Patients wanting to reduce the number of hypoglycaemic events from three per month to none were willing to pay SEK 419 (euro37.17) per month. Patients valued a 1 percentage point reduction in HbA(1c) at SEK 414 (euro36.72) per month. Participants preferred taking tablets to injections and required a compensation of SEK 376 (euro33.35) to accept one injection/day. Injections independent of meals were preferred to injections with meals (WTP: SEK 140/euro12.42 per month). Potential limitations of this study are that the preferences expressed may not match preferences in real-life situations, and bias through the use of electronic questionnaire, which restricted participation to those with access to, and experience with, the internet. CONCLUSION: People with type 2 diabetes were willing to pay a considerable amount of money each month to lose weight, reduce or avoid hypoglycaemic events and reduce HbA(1C).

Management of severe hypoglycaemia: cultural similarities, differences and resource consumption in three European countries.

BACKGROUND: To investigate the characteristics of people with insulin-treated diabetes, who have experienced severe hypoglycaemic events (SHEs), in Germany, Spain or UK. METHODS: Patients with type 1 (n=319) or insulin-treated type 2 diabetes (n=320) who had experienced ≥ 1 SHE in the preceding year were enrolled. Their median age was 53 years (range, 16-94 years). Data were collected using a questionnaire administered by an experienced interviewer. RESULTS: The median number of reported SHEs was 2-3 in 12 months. Most events (69%) occurred at home, usually during the day or evening (74%) and most commonly due to insufficient food consumption (45%). In patients whose hypoglycaemia awareness was tested, 68% had normal awareness. Patients requiring emergency healthcare treatment frequently had impaired hypoglycaemia awareness, and developed hypoglycaemic coma more often. Hospital treatment was usually provided in an emergency department (72-94%). The duration of stay was longest in Germany. Following a SHE, patients receiving professional treatment were more likely to: consult their physician, test their blood glucose more often, adjust insulin dose and receive self-management training. CONCLUSIONS: This survey of diabetes patients aged 16-94 years showed that SHEs represent a substantial burden on national healthcare systems in Germany, UK and Spain. The pattern of occurrence and treatment was similar in all three countries, despite differences in cultures and healthcare systems.

Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications.

Glutathione transferase alpha as a marker for tubular damage after trichloroethylene exposure.

To investigate possible persistent nephrotoxic effects of trichloroethylene (TRI), a retrospective study was carried out on 39 workers exposed to high levels of TRI from 1956 to 1975. Total protein levels in urine, as well as serum and urine creatinine and serum urea were unchanged in comparison with the control. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was applied to differentiate between tubular and/or glomerular dysfunction. Urinary excretion of alpha-1-microglobulin and glutathione transferase (GST) alpha, as markers of proximal tubular damage, were correlated with the SDS-PAGE patterns of urinary proteins both in the TRI exposed and the control group. GST alpha was found in elevated concentrations in the urine of the TRI-exposed workers. No increase of urinary GST alpha was observed in the control group, even when alpha-1-microglobulin was elevated as a result of non-toxic damage. Both in the control and exposed groups, GST pi, a marker of distal tubular damage, was in the normal range. The results show that chronic exposure to high doses of TRI causes persistent changes to the proximal tubular system of the kidney and that GST alpha excretion into the urine is a marker well suited for quantitation of the extent of renal damage.

ENVIRONMENTAL AUDITING: Assessing Biotic Integrity of Streams: Effects of Scale in Measuring the Influence of Land Use/Cover and Habitat Structure on Fish and Macroinvertebrates.

/ Fish and macroinvertebrate assemblage composition, instream habitat features and surrounding land use were assessed in an agriculturally developed watershed to relate overall biotic condition to patterns of land use and channel structure. Six 100-m reaches were sampled on each of three first-order warm-water tributaries of the River Raisin in southeastern Michigan. Comparisons among sites and tributaries showed considerable variability in fish assemblages measured with the index of biotic integrity, macroinvertebrate assemblages characterized with several diversity indexes, and both quantitative and qualitative measurements of instream habitat structure. Land use immediate to the tributaries predicted biotic condition better than regional land use, but was less important than local habitat variables in explaining the variability observed in fish and macroinvertebrate assemblages. Fish and macroinvertebrates appeared to respond differently to landscape configuration and habitat variables as well. Fish showed a stronger relationship to flow variability and immediate land use, while macroinvertebrates correlated most strongly with dominant substrate. Although significant, the relationships between instream habitat variables and immediate land use explained only a modest amount of the variability observed. A prior study of this watershed ascribed greater predictive power to land use. In comparison to our study design, this study covered a larger area, providing greater contrast among subcatchments. Differences in outcomes suggests that the scale of investigation influences the strength of predictive variables. Thus, we concluded that the importance of local habitat conditions is best revealed by comparisons at the within-subcatchment scale. KEY WORDS: Stream; Biomonitoring; Land use; Scale; Habitat; Fish; Macroinvertebrates

Renal cell cancer correlated with occupational exposure to trichloroethene.

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).

Influence of polymorphisms of GSTM1 and GSTT1 for risk of renal cell cancer in workers with long-term high occupational exposure to trichloroethene.

Suspected nephrocarcinogenic effects of trichloroethene (TRI) in humans are attributed to metabolites derived from the glutathione transferase (GST) pathway. The influence of polymorphisms of GSTM1 and GSTT1 isoenzymes on the risk of renal cell cancer in subjects having been exposed to high levels of TRI over many years was investigated. GSTM1 and GSTT1 genotypes were determined by internal standard controlled polymerase chain reaction. Fourty-five cases with histologically verified renal cell cancer and a history of long-term occupational exposure to high concentrations of TRI were studied. A reference group consisted of 48 workers from the same geographical region with similar histories of occupational exposures to TRI but not suffering from any cancer. Among the 45 renal cell cancer patients, 27 carried at least one functional GSTM1 gene (GSTT1 +) and 18 at least one functional GSTT1 gene (GSTT1 +). Among the 48 reference workers, 17 were GSTM1 + and 31 were GSTT1 +. Odds ratio for renal cell cancer were 2.7 for GSTM1 + individuals (95% CI, 1.18-6.33; P < 0.02) and 4.2 for GSTT1 + individuals (95% CI, 1.16-14.91; P < 0.05), respectively. The data support the present concept of the nephrocarcinogenicity of TRI.

Increased incidence of renal cell tumors in a cohort of cardboard workers exposed to trichloroethene.

A retrospective cohort study was carried out in a cardboard factory in Germany to investigate the association between exposure to trichloroethene (TRI) and renal cell cancer. The study group consisted of 169 men who had been exposed to TRI for at least 1 year between 1956 and 1975. The average observation period was 34 years. By the closing day of the study (December 31, 1992) 50 members of the cohort had died, 16 from malignant neoplasms. In 2 out of these 16 cases, kidney cancer was the cause of death, which leads to a standard mortality ratio of 3.28 compared with the local population. Five workers had been diagnosed with kidney cancer: four with renal cell cancers and one with a urothelial cancer of the renal pelvis. The standardized incidence ratio compared with the data of the Danish cancer registry was 7.97 (95% CI: 2.59-18.59). After the end of the observation period, two additional kidney tumors (one renal cell and one urothelial cancer) were diagnosed in the study group. The control group consisted of 190 unexposed workers in the same plant. By the closing day of the study 52 members of this cohort had died, 16 from malignant neoplasms, but none from kidney cancer. No case of kidney cancer was diagnosed in the control group. The direct comparison of the incidence on renal cell cancer shows a statistically significant increased risk in the cohort of exposed workers. Hence, in all types of analysis the incidence of kidney cancer is statistically elevated among workers exposed to TRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Group treatment of patients with irritable bowel syndrome.

Irritable bowel syndrome, a chronic illness affecting a large segment of the population, has no known anatomic etiology. Symptoms are precipitated or aggravated by stress or emotional factors as well as diet, drugs and hormones. This article describes the illness and a group treatment approach which takes into account developmental antecedents, communication deficits and existential issues.