The rôle of contact allergens and aeroallergens in facial dermatitis (FD) was studied. 114 cases of FD were divided into 3 groups. Group 1 comprised 47 cases of facial cosmetic dermatitis (FCD), in which all patients had a history of dermatitis related to cosmetics clinically; group 2 comprised 15 cases of seasonal facial dermatitis (SFD); Group 3 comprised 52 cases of other FD (OFD) that could not be categorized as FCD or SFD. Reactions to contact allergens and aeroallergens were detected using patch testing and intradermal testing, respectively, with non-facial eczematous skin disease patients serving as controls. The positivity rate for each allergen between different groups was compared by the chi2-test. The results show that the positivity rate for fragrance mix in FCD is much higher than in non-FCD (27.7% versus 6.7% in SFD, 7.6% in OFD and 6% in eczema patients, p<0.05). No significant difference was detected for other common allergens, such as PPD, rubber mix, nickel sulfate, and colophonium (p>0.05 for all). These results suggest that fragrance mix contains the main contact allergens in FCD. Patch testing with patients' own products also yields high numbers of relevant results in FCD and OFD. No relevant patch test results were found in SFD, indicating that contact allergy may not be relevant to SFD. No significant difference was observed between intradermal skin reactions to aeroallergens, including pollens and moulds, in SFD, OFD, FCD and controls. These results suggest that Type I reactions to aeroallergens may not be relevant in FD. The rôle of aeroallergens in FD needs to be studied further.

OBJECTIVE

This crossover study investigated the effect of consuming a beverage that contains soluble fiber dextrin (SFD) on appetite and food intake in adults to test the hypothesis that beverages that contain 10 or 20 g of fiber from SFD would be more satiating than the control beverage.

METHODS

Forty-one participants consumed lunch with a beverage that contained 0 g, 10 g, or 20 g of fiber from SFD. Appetite questionnaires were completed and blood samples collected immediately before lunch and at regular intervals over the following 150 min. Then, participants were provided with an afternoon snack and the amount eaten was recorded. Participants then left the laboratory but were asked to complete hourly appetite questionnaires and record food intake for the remainder of the day.

RESULTS

Consuming SFD had no effect on appetite over the 150 min after consumption of the lunch meal (P>> 0.05). Hunger and desire to eat were lower and fullness higher after consumption of the beverage that contained 20 g of fiber from SFD (P < 0.05) after participants left the laboratory. There was no effect of consuming SFD on food intake at the snack meal or for the rest of the day (P>> 0.05). Plasma glucose-dependent insulintropic polypeptide was lower during the 150 min after consumption of 20 g fiber from the SFD beverage (P < 0.05). There was no treatment effect on the plasma concentration of other biomarkers of glycemic response or appetite (P>> 0.05).

CONCLUSIONS

Overall, the study results did not show an effect of SFD on appetite, food intake, and plasma markers of appetite for the first 150 min postconsumption. Further research is required to quantify how SFD influences appetite several hours after consumption.

A total of 283 patients with somatoform disorder (SFD) seen in a psychiatry clinic were surveyed and their diagnostic subtypes, demographic features, and comorbidities, analyzed. The results indicate that: (i) SFD comprises 5.8% of first-visit outpatients; (ii) undifferentiated SFD (USFD) and SFD not otherwise specified (SFD-NOS) account for the majority of patients; (iii) there are 1.7-fold more women than men; (iv) age of onset is lower in patients with somatization disorder or body dysmorphic disorder and higher in patients with hypochondriasis or pain disorder; (v) the mean number of years of education was 11.2 years; and (vi) comorbid illness were seen in 24.8% of patients, and included mood disorder, anxiety disorder, and personality disorder, as well as borderline intellectual functioning and mental retardation. The data indicate that the majority of patients with SFD are given a diagnosis of residual category, such as USFD or SFD-NOS, and that the age of onset varies depending on the diagnostic subtype. SFD was more frequently seen in women, associated with comorbidities.

A serum assay was performed on 605 women for pregnancy-specific beta 1-glycoprotein (SP-1) between 31 and 34 weeks' gestation. SP-1 was also estimated for 255 of these women between 15 and 20 weeks' gestation, coincidental with maternal serum alpha-fetoprotein (AFP) screening. A clinical classification of pregnancy outcome was constructed for ech group. SP-1 values at 31 to 34 weeks' gestation in pregnancies that resulted in the birth of a small-for-dates (SFD) infant were statistically different from those in normal pregnancies (p less than 0.001). A value of 100 mg per liter was chosen as a suitable discriminatory level at 31 to 34 weeks, below which SP-1 had a sensitivity of 64%, a predictive value of 24%, and defined a relative risk of 5.3 for SFD infants. These parameters compare favorably with published data on the use of human placental lactogen as a screening test. No statistical relationship was found between SP-1 values at 31 to 34 weeks and birth weight, placental weight, parity, or other abnormal pregnancy outcomes. SP-1 screening at 15 to 20 weeks' gestation showed no correlation with serum AFP or with other parameters studied.

The purpose of the present research is to establish a novel nanosizing technique starting from wet nano-milling, named "dry nanosuspension" technique for poorly water-soluble drugs. The spray freeze-drying (SFD) method was applied instead of the spray-drying one previously developed. Drug particles were milled in the aqueous solution of dispersing agents using an oscillating beads-milling apparatus. The milled nanosuspension was sprayed to the surface of liquid nitrogen, and the resultant iced droplets were freeze-dried to obtain the powdery product. The loading ratio of a dispersing agent was investigated to enhance its redispersing property. Dry nanosuspension, which could be spontaneously dispersed into original nanosuspension in water, was obtained by SFD process. It was assumed that self dispersion property would be attributed to its structure with porous network, in which the primary milled drug crystals were embedded. Such unique structure contributed greatly to immediate release behaviors of the drug in gastrointestinal buffered media. These pharmaceutical properties were enhanced by increasing the ratio of the dispersing agent to the drug and the solid content in suspension to be sprayed. The present technique via wet milling and spray freeze-drying processes would be a novel dissolution-enhanced technology for poorly water-soluble drugs.

As shown in our previous report surfactant lipoprotein concentration (SLPC) in amniotic fluid measured by sucrose density gradient centrifugation predicts accurately the risk of RDS. In this study SLPC estimations were made on 91 amniotic fluid samples from abnormal pregnancies, spontaneous premature deliveries and anencephalies. The results were as follows. SLPCs increased in placental insufficiency and severe preeclampsia, especially associated with SFD infant, on the other hand, SLPCs decreased in maternal diabetes (Class B), Rh-isoimmunization and anencephaly as compared with normal pregnancy. In most of premature deliveries SLPCs were higher than those of normal pregnancies except for RDS cases. Present evidence suggests that the maturation of fetal lung is accelerated in severe preeclampsia and placental insufficiency and is delayed in maternal diabetes (Class B), Rh-isoimmunization and anencephaly, and it is considered that in spontaneous premature delivery surfactant production in fetal lung is not accelerated but surfactant excretion from fetal lung into amniotic fluid is enhanced by effect of uterine relaxant such as isoxsuprine or terbutaline.

The goal of this study was to investigate small field output factors (OFs) for flat-tening filter-free (FFF) beams on a dedicated stereotactic linear accelerator-based system. From this data, the collimator exchange effect was quantified, and detector-specific correction factors were generated. Output factors for 16 jaw-collimated small fields (from 0.5 to 2 cm) were measured using five different detectors including an ion chamber (CC01), a stereotactic field diode (SFD), a diode detector (Edge), Gafchromic film (EBT3), and a plastic scintillator detector (PSD, W1). Chamber, diodes, and PSD measurements were performed in a Wellhofer water tank, while films were irradiated in solid water at 100 cm source-to-surface distance and 10 cm depth. The collimator exchange effect was quantified for rectangular fields. Monte Carlo (MC) simulations of the measured configurations were also performed using the EGSnrc/DOSXYZnrc code. Output factors measured by the PSD and verified against film and MC calculations were chosen as the benchmark measurements. Compared with plastic scintillator detector (PSD), the small volume ion chamber (CC01) underestimated output factors by an average of -1.0% ± 4.9% (max. = -11.7% for 0.5 × 0.5 cm2 square field). The stereotactic diode (SFD) overestimated output factors by 2.5% ± 0.4% (max. = 3.3% for 0.5 × 1 cm2 rectangular field). The other diode detector (Edge) also overestimated the OFs by an average of 4.2% ± 0.9% (max. = 6.0% for 1 × 1 cm2 square field). Gafchromic film (EBT3) measure-ments and MC calculations agreed with the scintillator detector measurements within 0.6% ± 1.8% and 1.2% ± 1.5%, respectively. Across all the X and Y jaw combinations, the average collimator exchange effect was computed: 1.4% ± 1.1% (CC01), 5.8% ± 5.4% (SFD), 5.1% ± 4.8% (Edge diode), 3.5% ± 5.0% (Monte Carlo), 3.8% ± 4.7% (film), and 5.5% ± 5.1% (PSD). Small field detectors should be used with caution with a clear understanding of their behaviors, especially for FFF beams and small, elongated fields. The scintillator detector exhibited good agreement against Gafchromic film measurements and MC simulations over the range of field sizes studied. The collimator exchange effect was found to be impor-tant at these small field sizes. Detector-specific correction factors were computed using the scintillator measurements as the benchmark.

In this study, zero-field percent depth dose (PDD) and tissue maximum ratio (TMR) for 6 MV x rays have been determined by extrapolation from dosimetric measurements over the field size range 1 x 1-10 x 10 cm2. The key to small field dosimetry is the selection of a proper dosimeter for the measurements, as well as the alignment of the detector with the central axis (CAX) of beam. The measured PDD results are compared with those obtained from Monte Carlo (MC) simulation to examine the consistency and integrity of the measured data from which the zero-field PDD is extrapolated. Of the six most commonly used dosimeters in the clinic, the stereotactic diode field detector (SFD), the PTW Pinpoint, and the Exradin A14 are the most consistent and produce results within 2% of each other over the entire field size range 1 x 1-40 x 40 cm2. Although the diamond detector has the smallest sensitive volume, it is the least stable and tends to disagree with all other dosimeters by more than 10%. The zero-field PDD data extrapolated from larger field measurements obtained with the SFD are in good agreement with the MC results. The extrapolated and MC data agree within 2.5% over the clinical depth range (dmax-30 cm), when the MC data for the zero field are derived from a 1 X 1 cm2 field simulation using a miniphantom (1 x 1 x 48 cm3). The agreement between the measured PDD and the MC data based on a full phantom (48 x 48 x 48 cm3) simulation is fairly good within 1% at shallow depths to approximately 5% at 30 cm. Our results seem to indicate that zero-field TMR can be accurately calculated from PDD measurements with a proper choice of detector and a careful alignment of detector axis with the CAX.

Periodical checkups on 206 infants were carried out in order to elucidate which of various factors would pose decisive influence upon the retardation of mental development after birth with the AIKEN method. Correlations between average DQ (development quotient) and figures of physical measurements at birth were sought after. Consequently, weeks of gestation, body weight, cephalic circumference and body length at birth revealed certain correlation with the retardation of mental development. Multiple regression analysis disclosed highly significant correlations of body length and cephalic circumference toward the birth weight. Therefore, both weeks of gestation and birth weight are the direct contributory factors to average development quotient. Based on this result, a prediction equation for the mental development after birth has been proposed. Low average DQ was found in high percentages among infants born with toxemia of pregnancy or premature rupture of membranes. However, it is suggested that they are not the direct causes of such retardation, but are rather provoking short weeks of gestation and low birth weight. In summary, the newborn with less than 37 weeks of gestation and below 2,000 grams of birth weight would be named and classified as a SFD (small for dates) with the problem for mental development (MD-SFD).

Significance: Spatial frequency domain imaging (SFDI) is a quantitative imaging method to measure absorption and scattering of tissue, from which several chromophore concentrations (e.g., oxy-/deoxy-/meth-hemoglobin, melanin, and carotenoids) can be calculated. Employing a method to extract additional spectral bands from RGB components (that we named cross-channels), we designed a handheld SFDI device to account for these pigments, using low-cost, consumer-grade components for its implementation and characterization.

Aim: With only three broad spectral bands (red, green, blue, or RGB), consumer-grade devices are often too limited. We present a methodology to increase the number of spectral bands in SFDI devices that use RGB components without hardware modification.

Approach: We developed a compact low-cost RGB spectral imager using a color CMOS camera and LED-based mini projector. The components' spectral properties were characterized and additional cross-channel bands were calculated. An alternative characterization procedure was also developed that makes use of low-cost equipment, and its results were compared. The device performance was evaluated by measurements on tissue-simulating optical phantoms and in-vivo tissue. The measurements were compared with another quantitative spectroscopy method: spatial frequency domain spectroscopy (SFDS).

Results: Out of six possible cross-channel bands, two were evaluated to be suitable for our application and were fully characterized (520 ± 20 nm; 556 ± 18 nm). The other four cross-channels presented a too low signal-to-noise ratio for this implementation. In estimating the optical properties of optical phantoms, the SFDI data have a strong linear correlation with the SFDS data (R2 = 0.987, RMSE = 0.006 for μa, R2 = 0.994, RMSE = 0.078 for μs').

Conclusions: We extracted two additional spectral bands from a commercial RGB system at no cost. There was good agreement between our device and the research-grade SFDS system. The alternative characterization procedure we have presented allowed us to measure the spectral features of the system with an accuracy comparable to standard laboratory equipment.

Keywords: digital micromirror device; low-resource settings; multispectral imaging; phantoms; skin; spatial frequency domain imaging.

UNASSIGNED

The ability to generate lung alveolar epithelial type II (ATII) cells from pluripotent stem cells (PSCs) enables the study of lung development, regenerative medicine, and modeling of lung diseases. The establishment of defined, scalable differentiation methods is a step toward this goal. This study intends to investigate the competency of small molecule induced mouse embryonic stem cell-derived definitive endoderm (mESC-DE) cells towards ATII cells.

UNASSIGNED

In this experimental study, we designed a two-step differentiation protocol. mESC line Royan B20 (RB20) was induced to differentiate into DE (6 days) and then into ATII cells (9 days) by using an adherent culture method. To induce differentiation, we treated the mESCs for 6 days in serum-free differentiation (SFD) media and induced them with 200 nM small molecule inducer of definitive endoderm 2 (IDE2). For days 7-15 (9 days) of induction, we treated the resultant DE cells with new differentiation media comprised of 100 ng/ml fibroblast growth factor (FGF2) (group F), 0.5 μg/ml hydrocortisone (group H), and A549 conditioned medium (A549 CM) (group CM) in SFD media. Seven different combinations of factors were tested to assess the efficiencies of these factors to promote differentiation. The expressions of DE- and ATII-specific markers were investigated during each differentiation step.

UNASSIGNED

Although both F and H (alone and in combination) promoted differentiation through ATII-like cells, the highest percentage of surfactant protein C (SP-C) expressing cells (~37%) were produced in DE-like cells treated by F+H+CM. Ultrastructural analyses also confirmed the presence of lamellar bodies (LB) in the ATII-like cells.

UNASSIGNED

These results suggest that hydrocortisone can be a promoting factor in alveolar fate differentiation of IDE2-induced mESC-DE cells. These cells have potential for drug screening and cell-replacement therapies.

A radiophotoluminescent (RPL) glass rod dosimeter (GRD) and a small active volume p-type silicon diode detector (stereotactic field detector, SFD) were used for the measurement of Gamma-Knife output factors. All measurements were done using a 16 cm diameter spherical polystyrene phantom with the detector at the focal spot of Gamma-Knife. The GRD system consists of small rod-shaped glass chip detectors and an automatic readout device. The output factors measured with GRD of the 14, 8 and 4 mm helmets relative to the 18 mm helmet are 0.981, 0.942 and 0.877, respectively. Similarly, the corresponding output factors measured with SFD are 0.980, 0.949 and 0.867, respectively. These output factors are comparable with the values given in a recent publication and the values recommended by Elekta, the manufacture. The angular dependence of these detectors is also measured using a linear accelerator-based stereotactic radiosurgery system. For the Gamma-Knife angle ranging from 6 to 36 degrees from the vertical axis, the measured angular dependence of the GRD is approximately 1.0% at a 4 MV x-ray beam. The response of SFD indicates approximately 3-4% directional dependence for the same angle range for a 6 MV x-ray beam. The Gamma-Knife helmet output factors measured with SFD are corrected for angular dependence. In summary, GRD can be a good candidate in measuring small field output factor. Due to an angular dependence the small p-type diode detector needs care when calculating the Gamma-Knife dose.

We present a double-coil apparatus designed to operate with in situ capability, which is strongly desired for superconductivity studies on recently discovered two-dimensional superconductors. Coupled with a scanning tunneling microscope, the study of both local and global superconductivity [for superconducting gap and superfluid density (SFD), respectively] is possible on an identical sample without sample degradations due to damage, contamination, or oxidation in an atmosphere. The performance of the double-coil apparatus was tested on atomically clean surfaces of non-superconducting Si(111)-7 × 7 and on superconducting films of 100 nm-thick Pb and 1.4 nm-ultrathin Pb. The results clearly show the normal-to-superconductor phase transition for Pb films with a strong SFD.

Objective: To demonstrate the differences in intrauterine fetal deaths and neonatal deaths between small for date (SFD) and Non-SFD neonates by applying a novel classification from both Z scores of placental weight (PW) and fetal/placental weight ratio (F/P) to small for gestational age (SGA) neonates. Methods: From 93,034 placentas/infants of mothers who vaginally delivered a singleton infant (Japan Perinatal Registry Network database 2013), SGA (n=7,780) was chosen according to the reference to Japanese neonatal growth chart. They were divided into two subgroups: SFD (body weight and height less than the 10^th percentile, n=3,379) and Non-SFD (only body weight less than the 10^th percentile, n=4,401). Z scores of PW and F/P based on the standard curves for sex-, parity-, and gestational-age-specific PW and F/P were calculated. The population was classified into 9 groups according to the combination of 'low vs. middle vs. high' i) PW Z score and ii) F/P Z score. In both i) and ii), ± 1.28 standard deviations in the Z scores were used for classifying low vs. middle vs. high, with 3×3 making 9 groups. From top-left to bottom-right, we labeled the groups as Group A to Group I. Results: SFD and Non-SFD neonates distributed in the same 6 groups (A, D, E, G, H, I). In group E, which was considered to be balanced placental and infant growth, the incidence of intrauterine fetal death was significantly higher in Non-SFD neonates than in SFD neonates. In group D, which was considered to be small placenta and balanced infant growth, the incidence of neonatal death was significantly higher in SFD neonates than in Non-SFD neonates. Conclusion: Assessment of SGA neonates by dividing them into SFD and Non-SFD neonates and application of a 9-group classification by PW and F/P Z scores were informative to understand the pathophysiological involvement of an imbalance between placental and fetal sizes.

Recently, Alfonso et al proposed a new formalism for the dosimetry of small and non-standard fields. The proposed new formalism is strongly based on the calculation of detector-specific beam correction factors by Monte Carlo simulation methods, which accounts for the difference in the response of the detector between the small and the machine specific reference field. The correct calculation of the detector-specific beam correction factors demands an accurate knowledge of the linear accelerator, detector geometry and composition materials. The present work shows that the field factors in water may be determined experimentally using the daisy chain correction method down to a field size of 1 cm × 1 cm for a specific set of detectors. The detectors studied were: three mini-ionization chambers (PTW-31014, PTW-31006, IBA-CC01), three silicon-based diodes (PTW-60018, IBA-SFD and IBA-PFD) and one synthetic diamond detector (PTW-60019). Monte Carlo simulations and experimental measurements were performed for a 6 MV photon beam at 10 cm depth in water with a source-to-axis distance of 100 cm. The results show that the differences between the experimental and Monte Carlo calculated field factors are less than 0.5%-with the exception of the IBA-PFD-for field sizes between 1.5 cm × 1.5 cm and 5 cm × 5 cm. For the 1 cm × 1 cm field size, the differences are within 2%. By using the daisy chain correction method, it is possible to determine measured field factors in water. The results suggest that the daisy chain correction method is not suitable for measurements performed with the IBA-PFD detector. The latter is due to the presence of tungsten powder in the detector encapsulation material. The use of Monte Carlo calculated [Formula: see text] is encouraged for field sizes less than or equal to 1 cm × 1 cm for the dosimeters used in this work.

In this study, two types of biodegradable polycation (PAsp(DET) homopolymer and PEG-PAsp(DET) copolymer) were applied as vectors for inhalable dry gene powders prepared by spray freeze drying (SFD). The prepared dry gene powders had spherical and porous structures with a 5~10-μm diameter, and the integrity of plasmid DNA could be maintained during powder production. Furthermore, it was clarified that PEG-PAsp(DET)-based dry gene powder could more sufficiently maintain both the physicochemical properties and in vitro gene transfection efficiencies of polyplexes reconstituted after powder production than PAsp(DET)-based dry gene powder. From an in vitro inhalation study using an Andersen cascade impactor, it was demonstrated that the addition of l-leucine could markedly improve the inhalation performance of dry powders prepared by SFD. Following pulmonary delivery to mice, both PAsp(DET)- and PEG-PAsp(DET)-based dry gene powders could achieve higher gene transfection efficiencies in the lungs compared with a chitosan-based dry gene powder previously reported by us.

With Cr4+:YAG as a saturable absorber, a passively Q-switched self-frequency-doubled (SFD) laser based on a trigonal Nd:Ca3NbGa3Si2O14 (Nd:CNGS) silicate crystal was demonstrated for the first time. The maximum average output power at 532 nm was 16.2 mW, and the corresponding pulse repetition frequency, single pulse energy, pulse duration and peak power were 2.25 kHz, 7.2 μJ, 13.7 ns, 0.53 kW, respectively. We also present a rate-equation model of such a passively Q-switched SFD laser showing a good agreement with the experiment. Nd:CNGS is a promising pulse SFD material for miniature all-solid-state visible light sources.

Obesity is a low-grade inflammatory disease that increases the risk for metabolic disorders. CD40-CD40L signaling plays a central role in obesity-induced inflammation. Genetic deficiency of CD40L in diet-induced obesity (DIO) ameliorates adipose tissue inflammation, hepatic steatosis and increases insulin sensitivity. Unexpectedly, absence of CD40 worsened insulin resistance and caused excessive adipose tissue inflammation and hepatosteatosis. To investigate whether deficiency of macrophage CD40 is responsible for the phenotype observed in the CD40-/- mice, we generated CD40flflLysMcre and fed them a standard (SFD) and 54% high fat obesogenic diet (HFD) for 13 weeks. No differences in body weight, adipose tissue weight, adipocyte size, plasma cholesterol or triglyceride levels could be observed between CD40flflLysMcre and wild type (WT) mice. CD40flflLysMcre displayed no changes in glucose tolerance or insulin resistance, but had higher plasma adiponectin levels when fed a SFD. Liver weights, liver cholesterol and triglyceride levels, as well as the degree of hepatosteatosis were not affected by absence of macrophage CD40. CD40flflLysMcre mice displayed a minor increase in adipose tissue leukocyte infiltration on SFD and HFD, which did not result in differences in adipose tissue cytokine levels. We here show that loss of macrophage CD40 signaling does not affect obesity induced metabolic dysregulation and indicates that CD40-deficiency on other cell-types than the macrophage is responsible for the metabolic dysregulation, adipose tissue inflammation and hepatosteatosis that are observed in CD40-/- mice.

OBJECTIVE

In a previous work, output ratio (ORdet) measurements were performed for the 800 MU/min CyberKnife(®) at the Oscar Lambret Center (COL, France) using several commercially available detectors as well as using two passive dosimeters (EBT2 radiochromic film and micro-LiF TLD-700). The primary aim of the present work was to determine by Monte Carlo calculations the output factor in water (OFMC,w) and the [Formula: see text] correction factors. The secondary aim was to study the detector response in small beams using Monte Carlo simulation.

METHODS

The LINAC head of the CyberKnife(®) was modeled using the PENELOPE Monte Carlo code system. The primary electron beam was modeled using a monoenergetic source with a radial gaussian distribution. The model was adjusted by comparisons between calculated and measured lateral profiles and tissue-phantom ratios obtained with the largest field. In addition, the PTW 60016 and 60017 diodes, PTW 60003 diamond, and micro-LiF were modeled. Output ratios with modeled detectors (ORMC,det) and OFMC,w were calculated and compared to measurements, in order to validate the model for smallest fields and to calculate [Formula: see text] correction factors, respectively. For the study of the influence of detector characteristics on their response in small beams; first, the impact of the atomic composition and the mass density of silicon, LiF, and diamond materials were investigated; second, the material, the volume averaging, and the coating effects of detecting material on the detector responses were estimated. Finally, the influence of the size of silicon chip on diode response was investigated.

RESULTS

Looking at measurement ratios (uncorrected output factors) compared to the OFMC,w, the PTW 60016, 60017 and Sun Nuclear EDGE diodes systematically over-responded (about +6% for the 5 mm field), whereas the PTW 31014 Pinpoint chamber systematically under-responded (about -12% for the 5 mm field). ORdet measured with the SFD diode and PTW 60003 diamond detectors were in good agreement with OFMC,w except for the 5 mm field size (about -7.5% for the diamond and +3% for the SFD). A good agreement with OFMC,w was obtained with the EBT2 film and micro-LiF dosimeters (deviation less than 1.4% for all fields investigated). [Formula: see text] correction factors for several detectors used in this work have been calculated. The impact of atomic composition on the dosimetric response of detectors was found to be insignificant, unlike the mass density and size of the detecting material.

CONCLUSIONS

The results obtained with the passive dosimeters showed that they can be used for small beam OF measurements without correction factors. The study of detector response showed that ORdet is depending on the mass density, the volume averaging, and the coating effects of the detecting material. Each effect was quantified for the PTW 60016 and 60017 diodes, the micro-LiF, and the PTW 60003 diamond detectors. None of the active detectors used in this work can be recommended as a reference for small field dosimetry, but an improved diode detector with a smaller silicon chip coated with tissue-equivalent material is anticipated (by simulation) to be a reliable small field dosimetric detector in a nonequilibrium field.

Within-tree variation in sap flow density (SFD) was measured in two isolated evergreen oak (Quercus ilex L.) trees growing in an oak savannah (dehesa) in southwest Spain. Sap flow was estimated by the constant heating method. Three sensors were installed in the trunk of each tree in three orientations: northeast (NE), northwest (NW) and south (S). Sap flow density was monitored continuously from May 18 to September 27, 1993. Daily values of SFD ranged between 500 and 4500 mm3 mm-2 day-1. There were significant differences in SFD between orientations; SFD was higher in the NE and NW orientations than in the S orientation. These differences were noted on both a daily and seasonal time scale, and were less pronounced on cloudy days and at the end of the drought period, when SFD was relatively low. Our results support the idea that branches of trees can be viewed as a collection of small independent plants.

OBJECTIVE

To determine the phenotypic and biochemical characteristics of the p.E139K missense variant in tissue inhibitor of metalloproteinase 3 (TIMP3) associated with Sorsby fundus dystrophy (SFD).

METHODS

The coding regions and adjacent intronic sequence of TIMP3 were amplified by polymerase chain reaction and then analyzed by bidirectional sequencing. Allele-specific PCR was used to determine the minimum allele frequency of the mutant allele in ethnically matched controls. Clinical examination and imaging of affected individuals with color fundus photography, scanning laser ophthalmoscope (fundal autofluorescence), and optical coherence tomography was performed. A mutant construct of the TIMP3 protein was created and expressed in human retinal pigment epithelium (ARPE19) cells, which were then assayed for oligomerization and intrinsic matrix metalloproteinase (MMP) inhibitory activity.

RESULTS

Three affected individuals from a family of Welsh origin each harbored one allele of the TIMP3 missense variant c.415 G>A, (p.E139K), which was not identified in 534 ethnically matched control chromosomes and thus presumed pathogenic. The mutant protein was shown to dimerize in culture cells and retain its MMP inhibitory activity. Retinal examination was variable between eyes of affected individuals and between family members. Drusen-like deposits were common to all three affected individuals and yellow subretinal deposits, exudative maculopathy, and geographic atrophy were also observed. Optical coherence tomography (OCT) images of affected individuals demonstrated hyperreflectivity of the RPE-photoreceptor-choroid complex.

CONCLUSIONS

The TIMP3 p.E139K mutation is another cause of SFD. It is the second TIMP3 sequence variant reported that does not affect the number of cysteine residues in the mutant protein yet dimerizes in vitro. The clinical presentation of this family is in keeping with previous clinical reports of this disorder.

To revisit the autosomal dominant Sorsby fundus dystrophy (SFD) as a syndromic condition including late-onset pulmonary disease. We report clinical and imaging data of ten affected individuals from 2 unrelated families with SFD and carrying heterozygous TIMP3 mutations (c.572A>> G, p.Y191C, exon 5, in family 1 and c.113C>> G, p.S38C, exon 1, in family 2). In family 1, all SFD patients older than 50 (two generations) had also a severe emphysema, despite no history of smoking or asthma. In the preceding generation, the mother died of pulmonary emphysema and she was blind after the age of 50. Her two great-grandsons (<20 years), had abnormal Bruch Membrane thickness, a sign of eye disease. In family 2, eye and lung diseases were also associated in two generations, both occurred later, and lung disease was moderate (bronchiectasis). This is the first report of a syndromic SFD in line with the mouse model uncovering the role of TIMP3 in human lung morphogenesis and functions. The TIMP3 gene should be screened in familial pulmonary diseases with bronchiectasis, associated with a medical history of visual loss. In addition, SFD patients should be advised to avoid tobacco consumption, to practice sports, and to undergo regular pulmonary examinations.

Prenatal nutrition is impaired in small-for-gestational-age infants. Serum amino acids may show some biochemical features related to the nutritional state of these children. We have carried out a study on serum and urine amino acids in 12 small-for-date infants (SFD) and 14 healthy newborns from birth to 1 month of life. SFD infants showed a high serum level of alanine and decreased concentrations of branched chain amino acids, aspartate, cystine and tryptophan at birth. The results are compatible with a protein malnutrition state. Levels of serum amino acids in SFD infants showed no differences in relation to normal infants after 1 month of rehabilitation with a diet consisting of an adapted milk formula.

Nanoparticles based on cellulose nanocrystals (CNC) and montmorillonite clay (MMT) were prepared using spray freeze-drying. The nanoparticles were then used as reinforcement to prepare nanocomposites with poly(lactic acid) (PLA) as the polymer matrix. The effect of spray freeze-dried CNC (SFD-CNC) and spray freeze-dried MMT (SFD-MMT) on the rheological and mechanical properties of PLA and its blends with poly[(butylene succinate)-co-adipate)] (PBSA) were investigated. An epoxy chain extender was used during preparation of the blends and nanocomposites to enhance the mechanical properties of the products. Different methods such as scanning electron microscopy, X-ray diffraction and adsorption/desorption analyses were used to characterize the prepared nanoparticles and their localization in the blends. Dynamic oscillatory shear behavior, elongational viscosity and mechanical characteristics of the nanocomposites of PLA and the blends were evaluated. The results obtained for nanocomposites filled with unmodified SFD-MMT were compared with those obtained when the filler was a commercial organically modified montmorillonite nanoclay (methyl-tallow-bis(2-hydroxyeethyl) quaternary ammonium chloride) (C30B), which was not spray freeze-dried.