Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression.

Dysregulation of the alternative pathway (AP) of the complement system is a significant contributor to age-related macular degeneration (AMD), a primary cause of irreversible vision loss worldwide. Here, we assess the contribution of the liver-produced complement factor H-related 4 protein (FHR-4) to AMD initiation and course of progression. We show that FHR-4 variation in plasma and at the primary location of AMD-associated pathology, the retinal pigment epithelium/Bruch's membrane/choroid interface, is entirely explained by three independent quantitative trait loci (QTL). Using two distinct cohorts composed of a combined 14,965 controls and 20,741 cases, we ascertain that independent QTLs for FHR-4 are distinct from variants causally associated with AMD, and that FHR-4 variation is not independently associated with disease. Additionally, FHR-4 does not appear to influence AMD progression course among patients with disease driven predominantly by AP dysregulation. Modulation of FHR-4 is therefore unlikely to be an effective therapeutic strategy for AMD.

Recurrent primary scrotal extramammary Paget disease: a case report and literature review.

Extramammary Paget disease (EMPD) is a rare malignant neoplasm arising in apocrine gland-rich skin, which may be classified as either of primary or secondary origin. Management of this condition is predominantly surgical, and is often characterised by lengthy diagnostic delays. Complete surgical excision is challenging, and local recurrence is common. Herein, we discuss a subtle presentation of recurrent scrotal EMPD in a 77-year-old male and review the available literature. Although relatively rare, the indistinct nature of this pathology merits special attention from treating surgeons, who are frequently responsible for initial management and follow-up. The risk of distant metastasis and concomitant prognostic implications necessitate a high clinical index of suspicion, and low threshold for definitive biopsy in similar cases.

Field-induced vortex-like textures as a probe of the critical line in reentrant spin glasses.

We study the evolution of the low-temperature field-induced magnetic defects observed under an applied magnetic field in a series of frustrated amorphous ferromagnets (Fe[Formula: see text]Mn[Formula: see text])[Formula: see text]P[Formula: see text]B[Formula: see text]Al[Formula: see text] ("a-Fe[Formula: see text]Mn[Formula: see text]"). Combining small-angle neutron scattering and Monte Carlo simulations, we show that the morphology of these defects resemble that of quasi-bidimensional spin vortices. They are observed in the so-called "reentrant" spin-glass (RSG) phase, up to the critical concentration [Formula: see text] which separates the RSG and "true" spin glass (SG) within the low temperature part of the magnetic phase diagram of a-Fe1-xMnx. These textures systematically decrease in size with increasing magnetic field or decreasing the average exchange interaction, and they finally disappear in the SG sample ([Formula: see text]), being replaced by field-induced correlations over finite length scales. We argue that the study of these nanoscopic defects could be used to probe the critical line between the RSG and SG phases.

The effects of pre-sleep consumption of casein protein on next-morning measures of RMR and appetite compared between sedentary pre- and postmenopausal women.

The purpose of the present study was to compare next-morning responses of RMR and appetite to pre-sleep consumption of casein protein (CP) in pre- and postmenopausal women. The study was a randomised, crossover, double-blind, placebo-controlled trial. Seven sedentary premenopausal (age: 19·9 (sd 1·2) years; BMI: 23·1 (sd 2·6) kg/m2) and seven sedentary postmenopausal (age: 56·4 (sd 4·9) years; BMI: 26·3 (sd 3·5) kg/m2) women participated. During visit one, anthropometrics and body composition were measured. Following visit one, subjects consumed either CP (25 g) or placebo (PL) ≥2 h after their last meal and ≤30 min prior to sleep on the night before visits two and three. Visits two and three occurred ≥1 week after visit one and were 48 h apart. During visits two and three, RMR (VO2), RER and appetite were measured via indirect calorimetry and visual analogue scale, respectively. Anthropometrics and body composition were analysed by one-way ANOVA. RMR and measures of appetite were analysed using a 2 × 2 (menopause status × CP/PL) repeated-measures ANOVA. Significance was accepted at P ≤ 0·05. RMR was significantly lower in postmenopausal compared with premenopausal women under both conditions (P = 0·003). When consumed pre-sleep CP did not alter RMR, RER or appetite compared with PL when assessed next morning in pre- and postmenopausal women. These data contribute to growing evidence that pre-sleep consumption of protein is not harmful to next-morning metabolism or appetite. In addition, these data demonstrate that menopause may not alter next-morning RMR, RER or appetite after pre-sleep consumption of CP.

Furnace for in situ and simultaneous studies of nano-precipitates and phase transformations in steels by SANS and neutron diffraction.

Interphase precipitation occurring during solid-state phase transformations in micro-alloyed steels is generally studied through transmission electron microscopy, atom probe tomography, and ex situ measurements of Small-Angle Neutron Scattering (SANS). The advantage of SANS over the other two characterization techniques is that SANS allows for the quantitative determination of size distribution, volume fraction, and number density of a statistically significant number of precipitates within the resulting matrix at room temperature. However, the performance of ex situ SANS measurements alone does not provide information regarding the probable correlation between interphase precipitation and phase transformations. This limitation makes it necessary to perform in situ and simultaneous studies on precipitation and phase transformations in order to gain an in-depth understanding of the nucleation and growth of precipitates in relation to the evolution of austenite decomposition at high temperatures. A furnace is, thus, designed and developed for such in situ studies in which SANS measurements can be simultaneously performed with neutron diffraction measurements during the application of high-temperature thermal treatments. The furnace is capable of carrying out thermal treatments involving fast heating and cooling as well as high operation temperatures (up to 1200 °C) for a long period of time with accurate temperature control in a protective atmosphere and in a magnetic field of up to 1.5 T. The characteristics of this furnace give the possibility of developing new research studies for better insight of the relationship between phase transformations and precipitation kinetics in steels and also in other types of materials containing nano-scale microstructural features.

Optimization of Time- and Code-Division-Multiplexed Readout for Athena X-IFU.

Readout of a large, spacecraft-based array of superconducting transition-edge sensors (TESs) requires careful management of the layout area and power dissipation of the cryogenic-circuit components. We present three optimizations of our time- (TDM) and code-division-multiplexing (CDM) systems for the X-ray Integral Field Unit (X-IFU), a several-thousand-pixel-TES array for the planned Athena-satellite mission. The first optimization is a new readout scheme that is a hybrid of CDM and TDM. This C/TDM architecture balances CDM's noise advantage with TDM's layout compactness. The second is a redesign of a component: the shunt resistor that provides a dc-voltage bias to the TESs. A new layout and a thicker Pd-Au resistive layer combine to reduce this resistor's area by more than a factor of 5. Third, we have studied the power dissipated by the first-stage SQUIDs (superconducting quantum-interference devices) and the readout noise versus the critical current of the first-stage SqUIDs. As a result, the X-IFU TDM and C/TDM SQUIDs will have a specified junction critical current of 5 µA. Based on these design optimizations and TDM experiments described by Durkin, et al. (these proceedings), TDM meets all requirements to be X-IFU's backup-readout option. Hybrid C/TDM is another viable option that could save spacecraft resources.

Demonstration of Athena X-IFU Compatible 40-Row Time-Division-Multiplexed Readout.

Time-division multiplexing (TDM) is the backup readout technology for the X-ray Integral Field Unit (X-IFU), a 3,168-pixel X-ray transition-edge sensor (TES) array that will provide imaging spectroscopy for ESA's Athena satellite mission. X-0IFU design studies are considering readout with a multiplexing factor of up to 40. We present data showing 40-row TDM readout (32 TES rows + 8 repeats of the last row) of TESs that are of the same type as those being planned for X-IFU, using measurement and analysis parameters within the ranges specified for X-IFU. Singlecolumn TDM measurements have best-fit energy resolution of (1.91 ± 0.01) eV for the Al Kα complex (1.5 keV), (2.10 ± 0.02) eV for Ti Kα (4.5 keV), (2.23 ± 0.02) eV for Mn Kα (5.9 keV), (2.40 ± 0.02) eV for Co Kα (6.9 keV), and (3.44 ± 0.04) eV for Br Kα (11.9 keV). Three-column measurements have best-fit resolution of (2.03 ± 0.01) eV for Ti Kα and (2.40 ± 0.01) eV for Co Kα. The degradation due to the multiplexed readout ranges from 0.1 eV at the lower end of the energy range to 0.5 eV at the higher end. The demonstrated performance meets X-IFU's energy-resolution and energy-range requirements. True 40-row TDM readout, without repeated rows, of kilopixel scale arrays of X-IFU-like TESs is now under development.

Expanding the Capability of Microwave Multiplexed Readout for Fast Signals in Microcalorimeters.

Microwave SQUID multiplexing has become a key technology for reading out large arrays of X-ray and gamma-ray microcalorimeters with mux factors of 100 or more. The desire for fast X-ray pulses that accommodate photon counting rates of hundreds or thousands of counts per second per sensor drives system design toward high sensor current slew rate. Typically, readout of high current slew rate events is accomplished by increasing the sampling rate, such that rates of order 1MHz may be necessary for some experiments. In our microwave multiplexed readout scheme, the effective sampling rate is set by the frequency of the flux-ramp modulation (f r) used to linearize the SQUID response. The maximum current slew rate between samples is then nominally Φ 0 f r/2M in (where M in is the input coupling) because it is generally not possible to distinguish phase shifts of > π from negative phase shifts of < -π. However, during a pulse, we know which direction the current ought to be slewing, and this makes it possible to reconstruct a pulse where the magnitude of the phase shift between samples is > π. We describe a practical algorithm to identify and reconstruct pulses that exceed this nominal slew rate limit on the rising edge. Using pulses produced by X-ray transition-edge sensors, we find that the pulse reconstruction has a negligible impact on energy resolution compared to arrival time effects induced by under-sampling the rising edge. This technique can increase the effective slew rate limit by more than a factor of two, thereby either reducing the resonator bandwidth required or extending the energy range of measurable photons. The extra margin could also be used to improve crosstalk or to decrease readout noise.

Red Wine Age Estimation by the Alteration of Its Color Parameters: Fourier Transform Infrared Spectroscopy as a Tool to Monitor Wine Maturation Time.

Color, phenolic content, and chemical age values of red wines made from Cretan grape varieties (Kotsifali, Mandilari) were evaluated over nine months of maturation in different containers for two vintages. The wines differed greatly on their anthocyanin profiles. Mid-IR spectra were also recorded with the use of a Fourier Transform Infrared Spectrophotometer in ZnSe disk mode. Analysis of Variance was used to explore the parameter's dependency on time. Determination models were developed for the chemical age indexes using Partial Least Squares (PLS) (TQ Analyst software) considering the spectral region 1830-1500 cm-1. The correlation coefficients (r) for chemical age index i were 0.86 for Kotsifali (Root Mean Square Error of Calibration (RMSEC) = 0.067, Root Mean Square Error of Prediction (RMSEP) = 0,115, and Root Mean Square Error of Validation (RMSECV) = 0.164) and 0.90 for Mandilari (RMSEC = 0.050, RMSEP = 0.040, and RMSECV = 0.089). For chemical age index ii the correlation coefficients (r) were 0.86 and 0.97 for Kotsifali (RMSEC 0.044, RMSEP = 0.087, and RMSECV = 0.214) and Mandilari (RMSEC = 0.024, RMSEP = 0.033, and RMSECV = 0.078), respectively. The proposed method is simpler, less time consuming, and more economical and does not require chemical reagents.

Magnetic Fluctuations, Precursor Phenomena, and Phase Transition in MnSi under a Magnetic Field.

The reference chiral helimagnet MnSi is the first system where Skyrmion lattice correlations have been reported. At a zero magnetic field the transition at T_{C} to the helimagnetic state is of first order. Above T_{C}, in a region dominated by precursor phenomena, neutron scattering shows the buildup of strong chiral fluctuating correlations over the surface of a sphere with radius 2π/ℓ, where ℓ is the pitch of the helix. It has been suggested that these fluctuating correlations drive the helical transition to first order following a scenario proposed by Brazovskii for liquid crystals. We present a comprehensive neutron scattering study under magnetic fields, which provides evidence that this is not the case. The sharp first order transition persists for magnetic fields up to 0.4 T whereas the fluctuating correlations weaken and start to concentrate along the field direction already above 0.2 T. Our results thus disconnect the first order nature of the transition from the precursor fluctuating correlations. They also show no indication for a tricritical point, where the first order transition crosses over to second order with increasing magnetic field. In this light, the nature of the first order helical transition and the precursor phenomena above T_{C}, both of general relevance to chiral magnetism, remain an open question.

Using experimental and computational energy equilibration to understand hierarchical self-assembly of Fmoc-dipeptide amphiphiles.

Despite progress, a fundamental understanding of the relationships between the molecular structure and self-assembly configuration of Fmoc-dipeptides is still in its infancy. In this work, we provide a combined experimental and computational approach that makes use of free energy equilibration of a number of related Fmoc-dipeptides to arrive at an atomistic model of Fmoc-threonine-phenylalanine-amide (Fmoc-TF-NH2) which forms twisted fibres. By using dynamic peptide libraries where closely related dipeptide sequences are dynamically exchanged to eventually favour the formation of the thermodynamically most stable configuration, the relative importance of C-terminus modifications (amide versus methyl ester) and contributions of aliphatic versus aromatic amino acids (phenylalanine F vs. leucine L) is determined (F > L and NH2 > OMe). The approach enables a comparative interpretation of spectroscopic data, which can then be used to aid the construction of the atomistic model of the most stable structure (Fmoc-TF-NH2). The comparison of the relative stabilities of the models using molecular dynamic simulations and the correlation with experimental data using dynamic peptide libraries and a range of spectroscopy methods (FTIR, CD, fluorescence) allow for the determination of the nanostructure with atomistic resolution. The final model obtained through this process is able to reproduce the experimentally observed formation of intertwining fibres for Fmoc-TF-NH2, providing information of the interactions involved in the hierarchical supramolecular self-assembly. The developed methodology and approach should be of general use for the characterization of supramolecular structures.

Differences in cardiac structure assessed by echocardiography between renal transplant recipients and chronic kidney disease patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in predialysis chronic kidney disease (CKD) and dialysis patients as well as in renal transplant recipients (RTRs). Left ventricular hypertrophy (LVH) starts early during the course of CKD and is a strong predictor of CVD in this population. Regression of LVH after a successful renal transplantation remains a debatable issue among investigators, whereas there is little data comparing echocardiographic measurements between patients with predialysis CKD and RTRs. AIM: The aim of this study was to compare echocardiographic measurements of LV structure and function between predialysis CKD patients and RTRs of similar renal function level. PATIENTS AND METHODS: We conducted a case control study with individual (1:2) matching from the Renal Transplant and the predialysis CKD Outpatient Clinic. For each of the 36 RTRs, two matched for gender, age and estimated glomerular filtration rate (eGFR) predialysis CKD outpatients (72 patients) were included. All patients underwent transthoracic echocardiography and LV mass, LV mass index [LVM and LVMI = LVM/BSA g/m(2)] and indices of systolic function were measured. In a subgroup of 12 RTRs we retrospectively assessed and compared the LVMI measurements at three different time points, during predialysis, dialysis and post transplant period. RESULTS: The prevalence of LVH was 33% in RTRs and 52% in CKD patients (ns). RTRs had significantly lower LVM and LVMI levels compared with predialysis CKD patients (P = .006 and P = .008) while the other echocardiographic indices did not differ. In the subgroup of 12 RTRs, post-transplant LVMI levels (105 ± 25 g/m(2)) were significantly lower in comparison with predialysis (147 ± 57 g/m(2)) and dialysis LVMI levels (169 ± 72 g/m(2)) (P = .01, P = .01, respectively). CONCLUSION: RTRs had significantly lower LVMI compared with predialysis CKD patients of similar age, renal function, hemoglobin and blood pressure level.

Geographical differentiation of dried lentil seed (Lens culinaris) samples using diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and discriminant analysis.

Diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and discriminant analysis were used for the geographical differentiation of dried lentil seed (Lens culinaris) samples. Specifically, 18 Greek samples and nine samples imported from other countries were distinguished using the 2250-1720 and 1275-955 cm⁻¹ spectral regions. The differentiation is complete. The combination of DRIFTS and discriminant analysis enables simple, rapid, cheap and accurate differentiation of commercial lentil seeds in terms of geographical origin.

Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Assessment of nonimmunologic factors in kidney transplant recipients according to Kidney Disease Improving Global Outcomes.

INTRODUCTION: Cardiovascular disease is the primary cause of death among kidney transplant recipients (KTRs), whereas chronic allograft nephropathy (CAN) is the main reason leading to end-stage chronic kidney disease. The etiologies of both entities include immunologic and nonimmunologic factors. The management of modifiable nonimmunologic parameters has recently been identified by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. The aim of our study was to assess the implementation of these guidelines in the outpatient kidney transplantation clinic of our hospital. PATIENT AND METHODS: We retrospectively monitored the records of 48 transplanted KTRs including 32 males of overall mean age 45.1 ± 10.7 years regarding control of anemia, dyslipidemia, mineral bone disorder (MBD), and blood pressure (BP) levels. Data were recorded every 6 months for 2 years, starting 1 year after renal transplantation. RESULTS: The estimated glomerular filtration rate of patients at baseline was 60.3 ± 18.8 mL/min/1.73 m(2) with no significant change during 2 years of follow-up. The control of anemia was satisfactory in 42 patients (88%) with hemoglobin values ≥ 11 g/dL during the follow-up. Regarding dyslipidemia management, the aggregate of patients showed fasting triglycerides ≤500 mg/dL in all measurements. The percentage of KTRs with LDL ≤100 mg/dL tended to improve from baseline versus the end of the study period (20.8% vs 41.7%). Serum calcium was satisfactorily controlled in 77% of patients, serum phosphorus in all patients, whereas parathyroid hormone (PTH) was abnormal in 60% of KTRs with chronic kidney disease stages 3-5. Finally, the BP goal of <130/80 mm Hg was achieved in approximately half of the patients. CONCLUSION: Control of nonimmunologic factors was satisfactory in terms of renal anemia and MBD, whereas dyslipidemia and BP levels were inadequately controlled. There is a clear need for better integration into clinical practice of KDIGO guidelines with regard to modifiable nonimmunologic factors.

Observation of reentrant integer quantum Hall states in the lowest Landau level.

Measurements on very low disorder two-dimensional electrons confined to relatively wide GaAs quantum well samples with tunable density reveal a close competition between the electron liquid and solid phases near the Landau level filling factor ν=1. As the density is raised, the fractional quantum Hall liquid at ν=4/5 suddenly disappears at a well-width dependent critical density, and then reappears at higher densities with insulating phases on its flanks. These insulating phases exhibit reentrant ν=1 integer quantum Hall effects and signal the formation of electron Wigner crystal states. Qualitatively similar phenomena are seen near ν=6/5.

Are females more responsive to emotional stimuli? A neurophysiological study across arousal and valence dimensions.

Men and women seem to process emotions and react to them differently. Yet, few neurophysiological studies have systematically investigated gender differences in emotional processing. Here, we studied gender differences using Event Related Potentials (ERPs) and Skin Conductance Responses (SCR) recorded from participants who passively viewed emotional pictures selected from the International Affective Picture System (IAPS). The arousal and valence dimension of the stimuli were manipulated orthogonally. The peak amplitude and peak latency of ERP components and SCR were analyzed separately, and the scalp topographies of significant ERP differences were documented. Females responded with enhanced negative components (N100 and N200), in comparison to males, especially to the unpleasant visual stimuli, whereas both genders responded faster to high arousing or unpleasant stimuli. Scalp topographies revealed more pronounced gender differences on central and left hemisphere areas. Our results suggest a difference in the way emotional stimuli are processed by genders: unpleasant and high arousing stimuli evoke greater ERP amplitudes in women relatively to men. It also seems that unpleasant or high arousing stimuli are temporally prioritized during visual processing by both genders.

Chiral paramagnetic skyrmion-like phase in MnSi.

We present a comprehensive study of chiral fluctuations in the reference helimagnet MnSi by polarized neutron scattering and neutron spin echo spectroscopy, which reveals the existence of a completely left-handed and dynamically disordered phase. This phase may be identified as a spontaneous Skyrmion phase: it appears in a limited temperature range just above the helical transition T_{C} and coexists with the helical phase at T_{C}.

An overview of structural features of DNA and RNA complexes with saffron compounds: Models and antioxidant activity.

Saffron is the red dried stigmas of Crocus sativus L. flowers and used both as a spice and as a drug in traditional medicine. Its numerous applications as an antioxidant and anticancer agent are due to its secondary metabolites and their derivatives (safranal, crocetin, dimethylcrocetin). In this work we are comparing the spectroscopic results and antioxidant activities of saffron components safranal, crocetin (CRT) and dimethylcrocetin (DMCRT) complexes with calf-thymus DNA (ctDNA) and transfer RNA (tRNA) in aqueous solution at physiological conditions Intercalative and external binding modes of saffron compounds to DNA and RNA were observed with overall binding constants of K(safranal)=1.24x10(3)M(-1), K(CRT)=6.20x10(3)M(-1) and K(DMCRT)=1.85x10(5)M(-1), for DNA adducts and K(safranal)=6.80x10(3)M(-1), K(CRT)=1.40x10(4)M(-1) and K(DMCRT)=3.40x10(4)M(-1) for RNA complexes. A partial B- to A-DNA transition occurred at high ligand concentrations, while tRNA remained in A-conformation in saffron-RNA complexes. The antioxidant activity of CRT, DMCRT and safranal was also tested by the DPPH (2,2-diphenyl-1-picrylhydrazyl) antioxidant activity assay and their IC(50) values were compared to that of well known antioxidants such as Trolox and Butylated Hydroxy Toluene (BHT). The IC(50) values were 95+/-1microg/mL for safranal and 18+/-1microg/mL for crocetin. The inhibition of DMCRT reached a point of 38.8%, which corresponds to a concentration of 40microg/mL.