Modal content measurements (S2) of negative curvature hollow-core photonic crystal fibers.

We present modal content measurements (S2) of two different negative curvature hollow-core photonic crystal fibers: a kagome fiber and an ice cream cone fiber. Their sensitivity towards mode matching, bending and polarization is analyzed. For the kagome fiber, a higher order mode suppression of 17dB under optimal conditions was achieved, and for the ice cream cone fiber there was a suppression of up to 42dB. Polarization turned out to be a critical parameter for good higher order mode suppression in both fibers.

Phase-stable, multi-µJ femtosecond pulses from a repetition-rate tunable Ti:Sa-oscillator-seeded Yb-fiber amplifier.

We present a high-power, MHz-repetition-rate, phase-stable femtosecond laser system based on a phase-stabilized Ti:Sa oscillator and a multi-stage Yb-fiber chirped-pulse power amplifier. A 10-nm band around 1030 nm is split from the 7-fs oscillator output and serves as the seed for subsequent amplification by 54 dB to 80 W of average power. The µJ-level output is spectrally broadened in a solid-core fiber and compressed to ~30 fs with chirped mirrors. A pulse picker prior to power amplification allows for decreasing the repetition rate from 74 MHz by a factor of up to 4 without affecting the pulse parameters. To compensate for phase jitter added by the amplifier to the feed-forward phase-stabilized seeding pulses, a self-referencing feed-back loop is implemented at the system output. An integrated out-of-loop phase noise of less than 100 mrad was measured in the band from 0.4 Hz to 400 kHz, which to the best of our knowledge corresponds to the highest phase stability ever demonstrated for high-power, multi-MHz-repetition-rate ultrafast lasers. This system will enable experiments in attosecond physics at unprecedented repetition rates, it offers ideal prerequisites for the generation and field-resolved electro-optical sampling of high-power, broadband infrared pulses, and it is suitable for phase-stable white light generation.

Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.

OBJECTIVE: Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. METHODS: PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. RESULTS: Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. CONCLUSION: Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence.

1009 nm continuous-wave ytterbium-doped fiber amplifier emitting 146 W.

In this Letter, we demonstrate a single-mode continuous-wave fiber laser amplifier emitting 146 W of average output power at a wavelength of 1009 nm. The wavelength and bandwidth of the seed oscillator are defined by a pair of fiber Bragg gratings. The seed is amplified in a two-stage ytterbium-doped rod-type amplifier to 146 W with a high slope efficiency of 64%, showing excellent beam quality and stability throughout the experiment. The ASE suppression is as high as 63 dB.

An observational cohort study on geriatric patient profile in an emergency department in the Netherlands.

BACKGROUND: Currently, Dutch emergency care systems focus on rapid emergency department (ED) patient management with short completion times, which may not meet specific geriatric care needs. METHODS: Six-week observational study in patients aged ≥70 years, attending the ED of VU University Medical Center (VUmc, Amsterdam, the Netherlands) during weekday peak presentation times (10 AM - 10 PM). RESULTS: During six weeks, a total of 183 patients aged ≥70 years attended the ED, of which 117 (63.9%) presented during weekday peak hours. One hundred patients with a median age of 81 (min-max; 70-97 years) were prospectively observed. The majority presented with fall-related complaints (30%), multiple comorbidities (≥3 in 50.0%) and polymedication (≥5 in 53.7%). Mean ED length of stay was 175.8 (range 20-399) minutes (n=98). Of the patients discharged to their usual residence prior to the ED visit (n=58), 36.2% returned to our ED within 30 days; one in five of these patients had initially presented with a fall. CONCLUSION: In this study, fall-related injuries were the most frequent presenting complaint during weekday peak presentation times in 70-plus patients. Of these, one in five discharged from the ED returned within 30 days. Our emergency care system may not adequately cover comprehensive ED geriatric assessment, or provide sufficient outpatient care after ED home discharge. We believe that EPs should be more aware of the complex problems encountered in acute geriatric patients and address follow-up care pathways such as geriatric outpatient services, more often in frail elderly patients discharged home.

Does frailty predict increased risk of falls and fractures? A prospective population-based study.

UNLABELLED: A frailty concept that includes psychological and cognitive markers was prospectively shown to be associated with increased risk of multiple falls and fractures among 1,509 community dwelling older adults, especially in those aged 75 and over. The predictive ability of frailty is not superior to falls history. INTRODUCTION: The concept of frailty has been defined with or without psychological and cognitive markers. Falls are associated with multiple risk factors, including cognitive and mood disorders. The purpose of this study was to investigate the association of a comprehensive concept of frailty and its components with falls and fractures in community-dwelling older adults and to compare its predictive ability with having a history of falls. METHODS: One thousand five hundred nine participants in the Longitudinal Aging Study Amsterdam aged ≥65 were assessed to determine fall history and the prevalence of nine frailty markers, including cognitive and psychological factors. The number of falls and time to second fall were prospectively registered for 1 year. Fractures were registered for 6 years. RESULTS: Frailty was significantly associated with time to second fall: hazard ratio of 1.53 [95% confidence interval (CI), 1.07-2.18] and area under the receiver operating characteristic curve (AUC) of 0.58 (CI, 0.53-0.62). In participants aged ≥75, frailty was associated with ≥2 falls: odds ratio (OR) of 1.74 (CI, 1.19-2.55) and AUC of 0.62 (CI, 0.55-0.68). Frailty, adjusted for age and sex, was significantly associated with ≥2 fractures: OR of 3.67 (CI, 1.47-9.15). The AUCs for falls history (aged ≥75) ranged from 0.62 (CI, 0.58-0.67) for ≥1 falls to 0.67 (CI, 0.59-0.74) for ≥3 falls. CONCLUSIONS: A concept of frailty including psychological and cognitive markers is associated with both multiple falls and fractures. However, frailty is not superior to falls history for the selection of old persons at increased risk of recurrent falls.

The impact of medication on vitamin D status in older individuals.

OBJECTIVE: Vitamin D deficiency and polypharmacy are common in the elderly. However, knowledge on the associations between the use of specific medicines and serum 25-hydroxyvitamin D (25(OH)D) is limited. The aim of this study was to (better) define the associations between the use of specific medicines and serum 25(OH)D. METHODS: Two different cohorts (1995/1996 and 2002/2003) from the Longitudinal Aging Study Amsterdam (LASA) were used for cross-sectional analyses. LASA is based on an age and sex-stratified random sample of the Dutch older population. Study participants were aged 65-88 years in the first cohort (n = 1301) and 55-65 years in the second cohort (n = 736). Serum 25(OH)D of users of several groups of medicines were compared with levels of non-users using multiple linear regression analysis. RESULTS: Of all participants, 75.4% (first cohort) and 61.1% (second cohort) were using at least one medicine. In both cohorts, the number of medicines was associated with lower serum 25(OH)D. In the first cohort, after adjustment for confounding, users of any kind of medicine, loop diuretics and inhaled corticosteroids (only men) had respectively 4.4 nmol/l (P<0.01), 4.7 nmol/l (P = 0.04) and 7.3 nmol/l (P = 0.02) lower serum 25(OH)D than non-users. In the second cohort, the use of oral antidiabetics, calcium-channel blockers and angiotensin-converting enzyme inhibitors was associated with respectively 7.4 nmol/l (P = 0.04), 7.7 nmol/l (P = 0.01) and 7.6 nmol/l (P<0.01) lower serum 25(OH)D. CONCLUSIONS: These data show that users of several medicines have lower serum 25(OH)D than non-users. Vitamin D supplementation may be considered in patients with chronic use of medicines.

Multifactorial evaluation and treatment of persons with a high risk of recurrent falling was not cost-effective.

SUMMARY: This study evaluated the cost-effectiveness of multifactorial evaluation and treatment of fall risk factors in community-dwelling older persons at high risk of falling. The intervention and usual care groups did not differ in fall risk or costs. The multifactorial approach was not cost-effective compared to usual care in this group. INTRODUCTION: International guidelines recommend multifactorial evaluation and tailored treatment of risk factors to reduce falling in older persons. The cost-effectiveness may be enhanced in high-risk persons. Our study evaluates the cost-effectiveness of multifactorial evaluation and treatment of fall risk factors in community-dwelling older persons at high risk of recurrent falling. METHODS: An economic evaluation was conducted alongside a randomised controlled trial. Participants (≥65 years) with a high risk of recurrent falling were randomised into an intervention (n = 106) and usual care group (n = 111). The intervention consisted of multifactorial assessment and treatment of fall risk factors. Clinical outcomes were proportions of fallers and utility during 1 year. Costs were measured using questionnaires at 3, 6 and 12 months after baseline and valued using cost prices, if available, and guideline prices. Differences in costs and cost-effectiveness were analysed using bootstrapping. Cost-effectiveness planes and acceptability curves were presented. RESULTS: During 1 year, 52% and 56% of intervention and usual care participants reported at least one fall, respectively. The clinical outcome measures did not differ between the two groups. The mean costs were Euro 7,740 (SD 9,129) in the intervention group and Euro 6,838 (SD 8,623) in the usual care group (mean difference Euro 902, bootstrapped 95% CI: -1,534 to 3,357). Cost-effectiveness planes and acceptability curves indicated that multifactorial evaluation and treatment of fall risk factors was not cost-effective compared with usual care. CONCLUSIONS: Multifactorial evaluation and treatment of persons with a high risk of recurrent falling was not cost-effective compared to usual care.

The SC15 protein of Schizophyllum commune mediates formation of aerial hyphae and attachment in the absence of the SC3 hydrophobin.

Disruption of the SC3 gene in the basidiomycete Schizophyllum commune affected not only formation of aerial hyphae but also attachment to hydrophobic surfaces. However, these processes were not completely abolished, indicating involvement of other molecules. We here show that the SC15 protein mediates formation of aerial hyphae and attachment in the absence of SC3. SC15 is a secreted protein of 191 aa with a hydrophilic N-terminal half and a highly hydrophobic C-terminal half. It is not a hydrophobin as it lacks the eight conserved cysteine residues found in these proteins. Besides being secreted into the medium, SC15 was localized in the cell wall and the mucilage that binds aerial hyphae together. In a strain in which the SC15 gene was deleted (DeltaSC15) formation of aerial hyphae and attachment were not affected. However, these processes were almost completely abolished when the SC15 gene was deleted in the DeltaSC3 background. The absence of aerial hyphae in the DeltaSC3DeltaSC15 strain can be explained by the inability of the strain to lower the water surface tension and to make aerial hyphae hydrophobic.

Immunolocalization of hydrophobin HYDPt-1 from the ectomycorrhizal basidiomycete Pisolithus tinctorius during colonization of Eucalyptus globulus roots.

• The immunolocalization of one of the hydrophobins of Pisolithustinctorius (HYDPt-1) is reported. Hydrophobin proteins play key roles in adhesion and aggregation of fungal hyphae, and it is already known that formation of ectomycorrhizas on eucalypt roots enhances the accumulation of hydrophobin mRNAs in the mycelium of Pisolithus tinctorius. • Purification of SDS-insoluble proteins from the mycelium of P. tinctorius showed the presence of a 13 kDa polypeptide with properties of class I hydrophobin. • Polyconal antibodies were raised against a recombinant HYDPt-1 polypeptide, and these were used for immunofluorescence-coupled transmission electron microscopy. • HYDPt-1 is a cell wall protein located at the surface of the hyphae with no preferential accumulation in the fungal cells of the different tissues of the ectomycorrhiza (i.e. extraradical hyphae, mantle or Hartig net).

Interfacial self-assembly of fungal hydrophobins of the lichen-forming ascomycetes Xanthoria parietina and X. ectaneoides.

In the symbiotic phenotype of the lichen-forming ascomycetes Xanthoria parietina and X. ectaneoides, a conglutinate, hydrophilic cortex surrounds a system of aerial hyphae with hydrophobic wall surfaces. In X. parietina freeze-fracture electron microscopy showed that a rodlet layer covers the fungal and algal wall surfaces. Extracts of hot SDS-insoluble wall residues isolated from both species contained a protein that revealed a rodlet layer upon interfacial self-assembly. The N-terminal sequence of the 10-kDa protein of X. ectaneoides served to clone cDNA fragments of XEH1 (H1 of X. ectaneoides) and XPH1 (H1 of X. parietina) by RT-PCR. Genomic DNA blot analysis with both lichenized species and the aposymbiotically cultured symbionts of X. parietina showed that XPH1 and XEH1 are fungal single copy genes. The deduced amino acid sequences of the two encoded proteins were 96% identical and showed the characteristics of class I hydrophobins.

Identification and characterization of a tri-partite hydrophobin from Claviceps fusiformis. A novel type of class II hydrophobin.

A new type of hydrophobin is encoded by an abundant mRNA of Claviceps fusiformis. The predicted amino-acid sequence of the protein, dubbed CFTH1, shows a putative signal sequence for secretion, followed by three class II hydrophobin domains each preceded by glycine/asparagine rich regions. SDS/PAGE analysis of 60% ethanol extractions of C. fusiformis mycelia from shaken cultures showed CFTH1 at the 50-55-kDa position. N-terminal sequencing of both untreated mature CFTH1 and of a fragment obtained by trypsin digestion revealed that CFTH1 is not processed between the hydrophobin domains. Mass spectroscopy showed a mass of about 36 500 Da, which is about 1500 Da higher than the mass predicted from the constituent amino acids, indicating post-translational modification but not glycosylation. Purified CFTH1 self-assembled at hydrophilic/hydrophobic interfaces and, after assembly at a water/air interface, it was found to be highly surface active. Antibodies raised against CFTH1 localized the protein in a mucilageous coat surrounding submerged vegetative hyphae in liquid shaken culture and, as a discrete layer of about 10 nm thickness at the surface of aerial hyphae of standing cultures, suggesting a role in the formation of aerial hyphae.

Structural characterization of the hydrophobin SC3, as a monomer and after self-assembly at hydrophobic/hydrophilic interfaces.

Hydrophobins are small fungal proteins that self-assemble at hydrophilic/hydrophobic interfaces into amphipathic membranes that, in the case of Class I hydrophobins, can be disassembled only by treatment with agents like pure trifluoroacetic acid. Here we characterize, by spectroscopic techniques, the structural changes that occur upon assembly at an air/water interface and upon assembly on a hydrophobic solid surface, and the influence of deglycosylation on these events. We determined that the hydrophobin SC3 from Schizophyllum commune contains 16-22 O-linked mannose residues, probably attached to the N-terminal part of the peptide chain. Scanning force microscopy revealed that SC3 adsorbs specifically to a hydrophobic surface and cannot be removed by heating at 100 degrees C in 2% sodium dodecyl sulfate. Attenuated total reflection Fourier transform infrared spectroscopy and circular dichroism spectroscopy revealed that the monomeric, water-soluble form of the protein is rich in beta-sheet structure and that the amount of beta-sheet is increased after self-assembly on a water-air interface. Alpha-helix is induced specifically upon assembly of the protein on a hydrophobic solid. We propose a model for the formation of rodlets, which may be induced by dehydration and a conformational change of the glycosylated part of the protein, resulting in the formation of an amphipathic alpha-helix that forms an anchor for binding to a substrate. The assembly in the beta-sheet form seems to be involved in lowering of the surface tension, a potential function of hydrophobins.

Physician's working diagnosis compared to the Euricterus Real Life Data Diagnostic Tool Trial in three jaundice databases: Euricterus Dutch, independent prospective and independent retrospective.

BACKGROUND/AIMS: In the European Union Euricterus Project on (sub)Icterus proforma, the history and physical examination items were to be used for the physician's working diagnosis (PWD) and 'among others, for the development of the real life data electronic diagnostic tool, Trial. Trial delivers diagnosis probabilities based on Bayes' Theorem (B), completed by Trial Algorithm (TA). We wanted to compare the diagnostic accuracies (PWD and Trial probabilities as a percentage of the final diagnosis (FD) in a patient population) in 3 Dutch databases. METHODOLOGY: The inclusion criteria for both Euricterus and Trial were age > or = 16 and bilirubin > or = 20 mmol/l. Euricterus data gathering took place at the bedside on a proforma with (among other questions) 79 questions on history and physical examination as well as the diagnosis levels for the PWD (1 alternative possible) and FD (17 disease categories, dc). Trial was developed on the data of 7,104 Euricterus patients and its data-entry Demo has the same questions. It calculates the probability of each diagnosis of the 17 dc as a percentage, as each significant finding is encountered (BO, Bayesian Overall). It can simultaneously calculate the resemblance of the patient's signs and symptoms to each disease concomitantly (BV, Bayesian Vertical), and to any subset of a disease. Any probability is further tested for compatibility using TA, a subset of BV, delivering TA-PWD, TA-BO and TA-BV. The Trial test patients came from 3 databases: a Euricterus Dutch Patients Random Sample EDRS (n = 184, internal database) and 2 independent databases: prospective P (n = 80) and retrospective R (n = 152), totalling 416 patients. RESULTS: The accuracies of PWD and Trial showed no differences between the databases, and the results are therefore pooled (n = 416). With testing on the highest probability found, the PWD accuracy was 78%, TA-PWD 81%, TA-BO 74% and TA-BV 72%. The true FD's were mentioned (at any probability) in the PWD in 86%, TA-PWD in 92%, TA-BO in 94% and TA-BV in 91% of the patients. Testing only patients whose FD was "certain" or whose data were without omissions did not improve accuracy. Testing on probability > 95% improved BO and BV accuracy, but not TA-BO or TA-BV. CONCLUSIONS: The Physician's Working Diagnosis accuracy was approximately 80% and did not greatly improve after TA. The Trial TA-BO and TA-BV accuracies were only slightly less than the PWD. For well-trained physicians, Trial strengthens the physician's judgment, and for those less trained (or those to be trained), it delivers a (sub)icterus diagnostic disease probability at nearly consultant level.

Atomic composition of the hydrophobic and hydrophilic membrane sides of self-assembled SC3p hydrophobin.

The hydrophobin SC3p of Schizophyllum commune self-assembles into a 10-nm-thick amphipathic membrane at hydrophilic-hydrophobic interfaces. X-ray photoelectron spectroscopy of the hydrophobic membrane side of SC3p, assembled in vitro, showed an atomic composition similar to the calculated composition of SC3p when glycosylation was taken into account. The atomic composition measured at the hydrophilic membrane side deviated from that at the hydrophobic side and indicated the presence of a lower number of peptide bonds. High levels of S and N were detected only on mycelia carrying hydrophobic aerial hyphae, as expected with assembled SC3p present at the surface of these hyphae.

The thn mutation of Schizophyllum commune, which suppresses formation of aerial hyphae, affects expression of the Sc3 hydrophobin gene.

The spontaneous and recessive mutation thn in the basidiomycete Schizophyllum commune suppresses the formation of aerial hyphae in the monokaryon and, if present as a double dose, the formation of both aerial hyphae and fruit-bodies in the dikaryon. In the monokaryon, the mutation prevents accumulation of mRNA of the Sc3 gene, and in the dikaryon it also prevents the accumulation of fruiting-specific mRNAs, including mRNAs of the Sc1 and Sc4 genes, which are homologous to the Sc3 gene. These three genes code for hydrophobins, a family of small hydrophobic cysteine-rich proteins. In the thn monokaryon, the only detectable change in synthesized proteins is the disappearance of an abundant protein of apparent Mr = 28 K from the culture medium and from the cell walls. Protein sequencing shows that this is the product of the Sc3 gene. The Sc3 hydrophobin is present in the walls of aerial hyphae as a hot-SDS-insoluble complex. Submerged hyphae excrete large amounts of the hydrophobin into the medium.

Translation of RNA from Schizophyllum commune in a wheat germ and rabbit reticulocyte cell-free system. Comparison of in vitro and in vivo products after two-dimensional gel electrophoresis.

Total RNA was isolated from the fungus Schizophyllum commune and translated in a wheat germ and a rabbit reticulocyte cell-free system. The in vitro products were analysed by two-dimensional gel electrophoresis. Both systems synthesized more than 600 distinct polypeptides, the vast majority of which (about 80%) was qualitatively and quantitatively the same. This demonstrates that the plant and animal system are very similar with respect to their specificity and efficiency in translating heterologous RNA. The patterns of proteins synthesized in vivo markedly differed from those produced in vitro; only 40% of the protein spots coincided on the gels. On the average the in vivo proteins were smaller.

Characterization of the genome of the basidiomycete Schizophyllum commune.

DNA of Schizophyllum commune was isolated both from mycelial cells and from protoplasts. Nuclear DNA was isolated after solubilization of the mitochondria with the detergent Nonidet. The G + C content of the nuclear DNA was 57%, calculated from its buoyant density (1.7165 g/ml) and from the Tm (77.4 degrees C in 15 mM NaCl/1.5 mM trisodium citrate). The buoyant density of the ribosomal cistrons was 1.707 g/ml. DNA isolated from purified mitochondria had a very low G + C content: 22% (rho = 1.6845 g/ml, Tm = 61.8 degrees C in 15 mM NaCl/1.5 mM trisodium citrate). Analysis of CsCl profiles and melting patterns suggested that mitochondrial DNA contains interspersed (A + T)-rich sequences. From reassociation analysis of sheared nuclear DNA the genome size of S. commune was determined to be 22.8 . 10(9) daltons. A small amount of DNA (0.5 . 10(9) daltons) bound to hydroxyapatite at zero time Cot. 7% of the genome (1.6 . 10(9) daltons) represented repetitive DNA.