Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment.

PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.

Ventral rectopexy with biological mesh: short-term functional results.

PURPOSE: Ventral mesh rectopexy (VMR) is an established, minimally invasive, nerve-sparing procedure for the treatment of various symptomatic morphological changes in the posterior pelvic compartment. We present the short-term functional outcome and patient satisfaction after laparoscopic and robotic VMR with biological mesh. METHODS: We analyzed data from 123 patients who underwent laparoscopic ventral mesh rectopexy (LVMR) or robotic ventral mesh rectopexy (RVMR) from August 2012 to January 2017. Included in these data were patient demographics, intra- and postoperative findings, Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), Cleveland Clinic Incontinence Score (CCIS), and patient satisfaction as measured by visual analog scale (0-10). RESULTS: Improvements in CCCS, CCIS, and ODS were statistically significant at 6 and 12 months (p < 0.001). Patient satisfaction was excellent at 6 and 12 months (8.2/10 and 8.3/10, respectively). The overall complication rate was 14%, with a major complication rate of 2%. No mesh-related complications were observed. The need for surgical re-intervention because of relapse, symptom persistence or recurrence, or new symptoms was 3%. Outcome appears to be similar between LVMR and RVMR. CONCLUSIONS: Both LVMR and RVMR with biological mesh are safe and effective in reducing symptoms, as measured by CCCS, CCIS, and ODS, and patient satisfaction is high.

Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers.

The model reaction of photoinduced donor-acceptor interaction in linked systems (dyads) has been used to study the comparative reactivity of a well-known anti-inflammatory drug, (S)-naproxen (NPX) and its (R)-isomer. (R)- or (S)-NPX in these dyads is linked to (S)-N-methylpyrrolidine (Pyr) using a linear or cyclic amino acid bridge (AA or CyAA), to give (R)-/(S)-NPX-AA-(S)-Pyr flexible and (R)-/(S)-NPX-CyAA-(S)-Pyr rigid dyads. The donor-acceptor interaction is reminiscent of the binding (partial charge transfer, CT) and electron transfer (ET) processes involved in the extensively studied inhibition of the cyclooxygenase enzymes (COXs) by the NPX enantiomers. Besides that, both optical isomers undergo oxidative metabolism by enzymes from the P450 family, which also includes ET. The scheme proposed for the excitation quenching of the (R)- and (S)-NPX excited state in these dyads is based on the joint analysis of the chemically induced dynamic nuclear polarization (CIDNP) and fluorescence data. The (1)H CIDNP effects in this system appear in the back electron transfer in the biradical-zwitterion (BZ), which is formed via dyad photoirradiation. The rate constants of individual steps in the proposed scheme and the fluorescence quantum yields of the local excited (LE) states and exciplexes show stereoselectivity. It depends on the bridge's length, structure and solvent polarity. The CIDNP effects (experimental and calculated) also demonstrate stereodifferentiation. The exciplex quantum yields and the rates of formation are larger for the dyads containing (R)-NPX, which let us suggest a higher contribution from the CT processes with the (R)-optical isomer.

Spin-Orbital Excitation Continuum and Anomalous Electron-Phonon Interaction in the Mott Insulator LaTiO_{3}.

Raman scattering experiments on stoichiometric, Mott-insulating LaTiO_{3} over a wide range of excitation energies reveal a broad electronic continuum which is featureless in the paramagnetic state, but develops a gap of ~800 cm^{-1} upon cooling below the Néel temperature T_{N}=146 K. In the antiferromagnetic state, the spectral weight below the gap is transferred to well-defined spectral features due to spin and orbital excitations. Low-energy phonons exhibit pronounced Fano anomalies indicative of strong interaction with the electron system for T>T_{N}, but become sharp and symmetric for T

Nicotinic acid effects on insulin sensitivity and hepatic lipid metabolism: an in vivo to in vitro study.

Our aim was to characterize the effects and the underlying mechanisms of the lipid-regulating agent Niaspan(®) on both insulin action and triglyceride decrease in 20 nondiabetic, dyslipidemic men with metabolic syndrome receiving Niaspan(®) (2 g/day) or placebo for 8 weeks in a randomized, cross-over study. The effects on plasma lipid profile were characterized at the beginning and the end of each treatment period; insulin sensitivity was assessed using the 2-step euglycemic hyperinsulinemic clamp and VLDL-triglyceride turnover by measuring plasma glycerol enrichment, both at the end of each treatment period. The mechanism of action of nicotinic acid was studied in HuH7 and mouse primary hepatocytes. Lipid profile was improved after Niaspan(®) treatment with a significant-28% decrease in triglyceride levels, a+17% increase in HDL-C concentration and unchanged levels of fasting nonesterified fatty acid. VLDL-tri-glyceride production rate was markedly reduced after Niaspan(®) (-68%). However, the treatment induced hepatic insulin resistance, as assessed by reduced inhibition of endogenous glucose production by insulin (0.7±0.4 vs. 1.0±0.5 mg/kg · min, p<0.05) and decrease in fasting hepatic insulin sensitivity index (4.8±1.8 vs. 3.2±1.6, p<0.05) in the Niaspan(®) condition. Nicotinic acid also reduced insulin action in HuH7 and primary hepatocytes, independently of the activation of hepatic PKCε. This effect was associated with an increase in diacylglycerol and a decrease in tri-glyceride contents that occurred in the absence of modification of DGAT2 expression and activity. Eight weeks of Niaspan(®) treatment in dyslipidemic patients with metabolic syndrome induce hepatic insulin resistance. The mechanism could involve an accumulation of diacylglycerol and an alteration of insulin signaling in hepatocytes.

Elemental topological insulator with tunable Fermi level: strained α-Sn on InSb(001).

We report on the epitaxial fabrication and electronic properties of a topological phase in strained α-Sn on InSb. The topological surface state forms in the presence of an unusual band order not based on direct spin-orbit coupling, as shown in density functional and GW slab-layer calculations. Angle-resolved photoemission including spin detection probes experimentally how the topological spin-polarized state emerges from the second bulk valence band. Moreover, we demonstrate the precise control of the Fermi level by dopants.

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target.

STUDY DESIGN: A pilot study measuring the levels of serum-soluble CD95 ligand (CD95L) in eight spinal cord-injured patients. OBJECTIVES: To determine the soluble concentration of CD95L in spinal cord injury (SCI) patients after trauma. METHODS: We collected blood samples from eight patients with acute traumatic SCI. Soluble CD95L serum levels were determined using an enzyme-linked immunosorbent assay. American Spinal Injury Association (ASIA) was determined according to ASIA classification. The patients were monitored, and venous blood was drawn after arrival at the hospital on the 1st and 3rd day and during the 1st, 2nd, 4th, 8th and 12th weeks after trauma. RESULTS: The average patient age was 48.1 years (18-86 years). Three patients were paraplegic (two incomplete, one complete), five were quadriplegic (one complete, four incomplete). The serum concentration of soluble CD95L (sCD95L) decreased during the 1st week (41 ng(- l)) and increased after the 2nd week in all eight patients. It peaked during the 4th week (68.5 ng (- l)) and reached a plateau during the 12th week (76.2 ng (- l)). There are many possible explanations for not being able to detect a statistical significance, one of course being the small sample size. CONCLUSION: Promising results for anti-CD95L therapy have already been documented in lab studies with rodents. Anti-CD95L blocks the pro-apoptotic and proinflammatory activity of membrane-bound CD95L during the acute phase of SCI. We observed that sCD95L levels are elevated during the subacute and intermediate phases of SCI. It would be of great interest to study a larger group of patients to determine whether higher sCD95 levels are correlated with improved or impaired neurological outcome or with increasing levels of autoimmune components in peripheral blood.

The effects of bed-rest and countermeasure exercise on the endocrine system in male adults: evidence for immobilization-induced reduction in sex hormone-binding globulin levels.

BACKGROUND AND AIM: There is limited data on the effects of inactivity (prolonged bed-rest) on parameters of endocrine and metabolic function; we therefore aimed to examine changes in these systems during and after prolonged (56- day) bed-rest in male adults. SUBJECTS AND METHODS: Twenty healthy male subjects underwent 8 weeks of strict bed-rest and 12 months of follow-up as part of the Berlin Bed Rest Study. Subjects were randomized to an inactive group or a group that performed resistive vibration exercise (RVE) during bed-rest. All outcome parameters were measured before, during and after bed-rest. These included body composition (by whole body dual X-ray absorptiometry), SHBG, testosterone (T), estradiol (E2), PRL, cortisol (C), TSH and free T3 (FT3). RESULTS: Serum SHBG levels decreased in inactive subjects but remained unchanged in the RVE group (p<0.001). Serum T concentrations increased during the first 3 weeks of bed-rest in both groups (p<0.0001), while E2 levels sharply rose with re-mobilization (p<0.0001). Serum PRL decreased in the control group but increased in the RVE group (p=0.021). C levels did not change over time (p≥0.10). TSH increased whilst FT3 decreased during bed-rest (p all ≤0.0013). CONCLUSIONS: Prolonged bed-rest has significant effects on parameters of endocrine and metabolic function, some of which are related to, or counteracted by physical activity.

Are commonly recommended dosages for vitamin D supplementation too low? Vitamin D status and effects of supplementation on serum 25-hydroxyvitamin D levels--an observational study during clinical practice conditions.

UNLABELLED: Vitamin D deficiency is associated with increased fracture risk. The observational study aimed to investigate vitamin D status and supplementation in ambulatory patients. Only 20% of patients had optimal serum 25-hydroxyvitamin D [25(OH)D] levels. Commonly recommended dosages were insufficient to achieve clinically relevant increase of 25(OH)D levels. Higher dosages were safe and effective under clinical practice conditions. INTRODUCTION: Vitamin D deficiency is associated with adverse health outcome. The study aimed to investigate vitamin D status and supplementation in ambulatory patients. METHODS: Nine hundred seventy-five women and 188 men were evaluated for bone status from January 2008 to August 2008 within an observational study; 104 patients (n = 70 osteoporosis) received follow-up after 3 months. Dosage of vitamin D supplementation was documented and serum 25(OH)D and parathyroid hormone (PTH) determined. RESULTS: In all patients (age, 60.4 ± 14.1 years), distribution of 25(OH)D was 56.3 ± 22.3 nmol/L (normal range, 52-182 nmol/L) and PTH 53.8 ± 67.5 ng/L (normal range, 11-43 ng/L). The proportion of patients with 25(OH)D < 25, 25 to <50, 50 to <75, ≥75 nmol/L was 7.5%, 33.3%, 38.9% and 20.2% in the total group and 20.1%, 38.5%, 30.8%, 10.6% at baseline in the follow-up group, respectively. After 3 months, 3.9% had still 25(OH)D < 25 nmol/L; only 12.5% achieved 25(OH)D ≥ 75 nmol/L. In osteoporosis patients, 25(OH)D increased more in those taking ≥1,500 (median, 3,000) IU vitamin D per day (33.1 ± 14.7 nmol/L) compared with ≤1,000 (median, 800) IU/day (10.6 ± 20.0 nmol/L) (p < 0.0008). PTH decreased more in patients taking ≥1,500 IU/day (-13.2 ± 15.2 ng/L) compared with ≤1,000 IU/day (-7.6 ± 19.2 ng/L; p = 0.29). 25(OH)D was negatively correlated to PTH (r = -0.49, p < 0.0001). An increase of 25(OH)D ≥ 75 nmol/L resulted in normalised PTH. CONCLUSION: Supplementation with higher vitamin D dosages (2,000-3,000 IU/day) is required to achieve a relevant increase of 25(OH)D and normalisation of PTH.

Additive impact of alfacalcidol on bone mineral density and bone strength in alendronate treated postmenopausal women with reduced bone mass.

OBJECTIVES: Assessment of additive impact of alfacalcidol 1 µg daily (Alfa) on bone mineral density (BMD) and on bone strength in postmenopausal women treated with alendronate 70 mg weekly + 500 mg calcium daily. SUBJECTS AND METHODS: In a randomized, double-blind, placebo controlled study, 279 postmenopausal women with osteoporosis or osteopenia participated (intention to treat analysis [ITT]; aged 73.6∓4.7 years) and were treated with 70 mg alendronate (ALN) weekly and 500 mg calcium daily for 36 months. In addition, these patients received either 1 µg alfacalcidol (Alfa) or placebo (PLC) daily. BMD was measured with Dual-Energy-X-ray-Absorptiometry (DXA) at the lumbar spine and proximal femur and at forearm and tibia with peripheral quantitative computed tomography (pQCT) at regular intervals for 36 months. RESULTS: DXA-BMD of lumbar spine (L1-4) increased after 36 months, by 6.65% (p<0.0001) in the Alfa/ALN group versus 4.17% (p<0.0001) in the PLC/ALN group. Group difference was significant after 3 years (p=0.026). At the end of the study, significant differences were found in favor of the Alfa/ALN group in trabecular density (tibia) (p=0.002), cortical density (midshaft tibia) (p=0.043), and bone strength (p=0.001). The remaining parameters showed no differences between the treatment arms, apart cortical bone density at midshaft radius. CONCLUSIONS: Alfacalcidol significantly increases the efficacy of alendronate treatment in osteopenic/osteoporotic postmenopausal women on spinal DXA-BMD, cortical and trabecular BMD of the tibia and also bending stiffness of the tibia.

Resistive vibration exercise attenuates bone and muscle atrophy in 56 days of bed rest: biochemical markers of bone metabolism.

UNLABELLED: During and after prolonged bed rest, changes in bone metabolic markers occur within 3 days. Resistive vibration exercise during bed rest impedes bone loss and restricts increases in bone resorption markers whilst increasing bone formation. INTRODUCTION: To investigate the effectiveness of a resistive vibration exercise (RVE) countermeasure during prolonged bed rest using serum markers of bone metabolism and whole-body dual X-ray absorptiometry (DXA) as endpoints. METHODS: Twenty healthy male subjects underwent 8 weeks of bed rest with 12 months follow-up. Ten subjects performed RVE. Blood drawings and DXA measures were conducted regularly during and after bed rest. RESULTS: Bone resorption increased in the CTRL group with a less severe increase in the RVE group (p = 0.0004). Bone formation markers increased in the RVE group but decreased marginally in the CTRL group (p < 0.0001). At the end of bed rest, the CTRL group showed significant loss in leg bone mass (-1.8(0.9)%, p = 0.042) whereas the RVE group did not (-0.7(0.8)%, p = 0.405) although the difference between the groups was not significant (p = 0.12). CONCLUSIONS: The results suggest the countermeasure restricts increases in bone resorption, increased bone formation, and reduced bone loss during bed rest.

Comparison of CT colonography, colonoscopy, sigmoidoscopy and faecal occult blood tests for the detection of advanced adenoma in an average risk population.

BACKGROUND AND AIMS: This prospective trial was designed to compare the performance characteristics of five different screening tests in parallel for the detection of advanced colonic neoplasia: CT colonography (CTC), colonoscopy (OC), flexible sigmoidoscopy (FS), faecal immunochemical stool testing (FIT) and faecal occult blood testing (FOBT). METHODS: Average risk adults provided stool specimens for FOBT and FIT, and underwent same-day low-dose 64-multidetector row CTC and OC using segmentally unblinded OC as the standard of reference. Sensitivities and specificities were calculated for each single test, and for combinations of FS and stool tests. CTC radiation exposure was measured, and patient comfort levels and preferences were assessed by questionnaire. RESULTS: 221 adenomas were detected in 307 subjects who completed CTC (mean radiation dose, 4.5 mSv) and OC; 269 patients provided stool samples for both FOBT and FIT. Sensitivities of OC, CTC, FS, FIT and FOBT for advanced colonic neoplasia were 100% (95% CI 88.4% to 100%), 96.7% (82.8% to 99.9%), 83.3% (95% CI 65.3% to 94.4%), 32% (95% CI 14.9% to 53.5) and 20% (95% CI 6.8% to 40.7%), respectively. Combination of FS with FOBT or FIT led to no relevant increase in sensitivity. 12 of 45 advanced adenomas were smaller than 10 mm. 46% of patients preferred CTC and 37% preferred OC (p<0.001). CONCLUSIONS: High-resolution and low-dose CTC is feasible for colorectal cancer screening and reaches sensitivities comparable with OC for polyps >5 mm. For patients who refuse full bowel preparation and OC or CTC, FS should be preferred over stool tests. However, in cases where stool tests are performed, FIT should be recommended rather than FOBT.

Mutations disrupting neuronal connectivity in the Drosophila visual system.

The photoreceptor neurons (R cells) of the Drosophila compound eye elaborate a precise array of neuronal connections in the brain. These projections exhibit target specificity and create topographic maps (retinotopy). We have screened histologically for mutations disrupting R cell connectivity in developing tissue. Eighty mutations were isolated from over 6000 ethylmethane sulfonate-mutagenized lines. Characterization of these mutations included genetic mosaic analysis to determine whether the gene is required in the retina or in the optic ganglia. Most mutations were found to affect connectivity indirectly by disrupting development more generally in the eye or brain. Genes were identified as candidates for playing direct roles in R cell connectivity by affecting axonal outgrowth (eddy), target recognition (limbo and nonstop), and retinotopy (limbo).

Changes in composition, structure and aboveground biomass over seventy-six years (1930-2006) in the Black Rock Forest, Hudson Highlands, southeastern New York State.

We sought to quantify changes in tree species composition, forest structure and aboveground forest biomass (AGB) over 76 years (1930-2006) in the deciduous Black Rock Forest in southeastern New York, USA. We used data from periodic forest inventories, published floras and a set of eight long-term plots, along with species-specific allometric equations to estimate AGB and carbon content. Between the early 1930s and 2000, three species were extirpated from the forest (American elm (Ulmus americana L.), paper birch (Betula papyrifera Marsh.) and black spruce (Picea mariana (nigra) (Mill.) BSP)) and seven species invaded the forest (non-natives tree-of-heaven (Ailanthus altissima (Mill.) Swingle) and white poplar (Populus alba L.) and native, generally southerly distributed, southern catalpa (Catalpa bignonioides Walt.), cockspur hawthorn (Crataegus crus-galli L.), red mulberry (Morus rubra L.), eastern cottonwood (Populus deltoides Bartr.) and slippery elm (Ulmus rubra Muhl.)). Forest canopy was dominated by red oak and chestnut oak, but the understory tree community changed substantially from mixed oak-maple to red maple-black birch. Density decreased from an average of 1500 to 735 trees ha(-1), whereas basal area doubled from less than 15 m(2) ha(-1) to almost 30 m(2) ha(-1) by 2000. Forest-wide mean AGB from inventory data increased from about 71 Mg ha(-1) in 1930 to about 145 Mg ha(-1) in 1985, and mean AGB on the long-term plots increased from 75 Mg ha(-1) in 1936 to 218 Mg ha(-1) in 1998. Over 76 years, red oak (Quercus rubra L.) canopy trees stored carbon at about twice the rate of similar-sized canopy trees of other species. However, there has been a significant loss of live tree biomass as a result of canopy tree mortality since 1999. Important constraints on long-term biomass increment have included insect outbreaks and droughts.

N-Methylmorpholine-N-oxide ring cleavage registration by ESR under heating conditions of the Lyocell process.

Thermal cleavage processes of N-methylmorpholine-N-oxide monohydrate (NMMO) were observed in pure NMMO as well as in cellulose/NMMO solutions by ESR at temperatures of the industrial Lyocell process ( approximately 370K). Generated radicals were attributed to the alkylnitroxyl type radicals -CH(2)-NO-CH(3) in NMMO and additional (and dominated) -CH(2)-NO-CH(2)- in cellulose/NMMO solutions. Formation of both radical types formed due to NMMO ring scission is suggested.

Chicken beta B1-crystallin gene expression: presence of conserved functional polyomavirus enhancer-like and octamer binding-like promoter elements found in non-lens genes.

Expression of the chicken beta B1-crystallin gene was examined. Northern (RNA) blot and primer extension analyses showed that while abundant in the lens, the beta B1 mRNA is absent from the liver, brain, heart, skeletal muscle, and fibroblasts of the chicken embryo, suggesting lens specificity. Promoter fragments ranging from 434 to 126 bp of 5'-flanking sequence (plus 30 bp of exon 1) of the beta B1 gene fused to the bacterial chloramphenicol acetyltransferase gene functioned much more efficiently in transfected embryonic chicken lens epithelial cells than in transfected primary muscle fibroblasts or HeLa cells. Transient expression of recombinant plasmids in cultured lens cells, DNase I footprinting, in vitro transcription in a HeLa cell extract, and gel mobility shift assays were used to identify putative functional promoter elements of the beta B1-crystallin gene. Sequence analysis revealed a number of potential regulatory elements between positions -126 and -53 of the beta B1 promoter, including two Sp1 sites, two octamer binding sequence-like sites (OL-1 and OL-2), and two polyomavirus enhancer-like sites (PL-1 and PL-2). Deletion and site-specific mutation experiments established the functional importance of PL-1 (-116 to -102), PL-2 (-90 to -76), and OL-2 (-75 to -68). DNase I footprinting using a lens or a HeLa cell nuclear extract and gel mobility shifts using a lens nuclear extract indicated the presence of putative lens transcription factors binding to these DNA sequences. Competition experiments provided evidence that PL-1 and PL-2 recognize the same or very similar factors, while OL-2 recognizes a different factor. Our data suggest that the same or closely related transcription factors found in many tissues are used for expression of the chicken beta B1-crystallin gene in the lens.

Exposure to beryllium and occurrence of lung cancer: a reexamination of findings from a nested case-control study.

OBJECTIVE: Our aim was to reanalyze a nested case-control study of beryllium and lung cancer because we identified analysis and study design issues that could have led to the elevated odds ratios obtained in the study. METHODS: We reanalyzed the data using nontransformed exposure metrics instead of log-transformed metrics used in the publication. We identified and examined effects on estimated odds ratios of imbalances between cases and controls caused by the control selection method. RESULTS: This reanalysis found no elevated odds ratios for any exposure variable. CONCLUSION: : Our conclusions differ from the authors' interpretation that the findings are due to a causal relationship between beryllium exposure and lung cancer. Our alternative explanation is that they may be due to methodological problems that could have been controlled by closer matching of controls to cases. CLINICAL SIGNIFICANCE: This study challenges conclusions made from a large case-control study concerning beryllium-lung cancer associations. Occupational medicine practitioners may want to integrate findings from this study into advice they give beryllium-exposed workers concerned about lung cancer.

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.

Crystal structure and the Mott-Hubbard gap in YTiO(3) at high pressure.

The crystal structure of YTiO(3) at high pressures up to 30 GPa has been investigated by means of synchrotron x-ray powder diffraction (T = 295 K). The variation of the Ti-O bond lengths with pressure evidences a distinct change in the distortion of the TiO(6) octahedra at around 10 GPa, which is discussed in terms of a pressure-driven spatial reorientation of the occupied Ti 3d(t(2g)) orbitals. Mid-infrared synchrotron microspectroscopy has been used to determine quantitatively the pressure-induced reduction of the optical bandgap of YTiO(3), and the results are interpreted on the basis of the structural and possible orbital orientation changes.

Multicenter evaluation of a new 4th generation HIV screening assay Elecsys HIV combi.

Fourth-generation screening assays which permit a simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody reduce the diagnostic window on average by four days in comparison to third-generation antibody assays. Recently, the new automated Elecsys HIV combi was compared in a multicenter study to alternative fourth- and third-generation assays, p24 antigen test and HIV-1 RNA RT-PCR. A total of 104 serocon-version panels, samples of the acute phase of infection after seroconversion (n = 33), anti-HIV-1 positive specimens (n = 572) from patients in different stages of the disease, 535 subtyped samples from different geographical locations, including group M (subtypes A-J) and group O, anti-HIV-2 positive sera (n = 364), dilutions of cell culture supernatants (n = 60) infected with different HIV-1 subtypes, selected performance panels, 8406 unselected samples from blood donors originating from different blood transfusion centers, 3810 unselected sera from daily routine and from hospitalized patients, 9927 unselected samples from South Africa and 1943 potentially interfering samples were tested with the Elecsys HIV combi. Elecsys HIV combi showed a comparable sensitivity to HIV-1 Ag stand-alone assays for early detection of HIV infection in seroconversion panels. The mean time delay of Elecsys HIV combi (last negative sample + 1 day) in comparison to HIV-1 RT-PCR for 92 panels tested with both methods was 3.23 days. The diagnostic window was reduced with Elecsys HIV combi between 1.56 and 5.32 days in comparison to third-generation assays. The specificity of Elecsys HIV combi in blood donors was 99.80% after repeated testing. Our results show that a fourth-generation assay with improved specificity and sensitivity like the Elecsys HIV combi is suitable for blood donor screening due to its low number of false positives and since it detects HIV p24 antigen with a comparable sensitivity to single antigen assays.