OBJECTIVE

To determine where in the treatment steps recommended by the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN) Asthma Guideline it is cost-effective to use salmeterol xinafoate/fluticasone propionate combination inhaler (SFC) (Seretide) compared with other inhaled corticosteroid (ICS) containing regimens (with and without a long acting beta-2 agonist (LABA)) for chronic asthma in adults and children.

METHODS

Meta-analyses of percentage symptom-free days (%SFD) were used within a cost-effectiveness model. Time spent in two asthma control health states, 'symptom-free' and 'with-symptoms' was used as the measure of differential treatment effectiveness. SFC was compared with varying doses of fluticasone propionate (FP) and beclometasone dipropionate (BDP) with or without a separate salmeterol inhaler, and with the budesonide/formoterol combination inhaler (BUD/FORM) (Symbicort). Drug costs, non-drug costs and quality adjusted life years (QALY) were incorporated into the analyses. Results are presented as cost per QALY ratios and uncertainty explored using probabilistic sensitivity analysis.

RESULTS

Compared with an increased dose of FP in adults, SFC either 'dominates' (i.e. cheaper and more effective) FP or the cost per QALY is 6852 pounds sterling. The cost per QALYs estimated in sensitivity analyses using BDP costs range from 5679 pounds sterling to 15,997 pounds sterling. For children the cost per QALY for SFC 50 Evohaler compared with an increased dose of FP is pound 15,739 pounds sterling. SFC is similarly clinically effective in improving %SFDs compared with FP plus salmeterol delivered in separate inhalers (mean differences for each dose comparison of -3.9 (low) (with a 95% confidence interval (CI): -12.96; 5.16); 4.10 (medium) (95% CI: -3.01; 11.21); -0.4 (high) (95% CI: -8.88; 8.08)) and BUD/FORM (mean difference of 0.40 (95% CI -3.69; 4.49)) in adults, and a cheaper SFC option is available at all doses (annual cost savings range from 18 pounds sterling-427 pounds sterling per patient). SFC was similarly effective compared with FP plus salmeterol in separate inhalers in children under 12 and also resulted in annual cost savings of between 47 pounds sterling and 77 pounds sterling. A number of other comparisons were also made and the results are available as electronic supplementary data.

CONCLUSIONS

This is the first analysis to estimate the cost-effectiveness of SFC in chronic asthma compared with multiple comparators and based on a systematic identification of relevant trials and data on %SFDs. The findings suggest that for adults and children uncontrolled on BDP 400 microg/day or equivalent it is a cost-effective option to switch to SFC (at an equivalent ICS dose) compared with increasing the dose of ICS. For adults and children aged 12 years and over who have passed this point and are uncontrolled on BDP 800 microg/day or equivalent, switching to SFC remains a cost-effective approach. Where an adult or child requires an ICS and a LABA to be co-prescribed, SFC is a cost-effective option compared with FP or BDP plus salmeterol delivered in separate inhalers. In adults who require combination therapy, SFC is a cost-effective option compared with BUD/FORM.

White adipose tissue (WAT) mitochondrial dysfunction is linked to the pathogenesis of obesity driven insulin resistance. Dietary conditions that alter fat mass are known to affect white adipocyte mitochondrial function, however, the impact of high calorie diets on white adipocyte mitochondria is not fully understood. The aim of this study is to assess the effect of a diet rich in saturated or polyunsaturated fat on mitochondrial unfolded protein response (UPRmt), a retrograde signaling response that maintains mitochondrial homeostasis, in epididymal WAT (eWAT). Mice were fed a low fat diet (LFD), saturated fat diet (SFD) or fish oil (unsaturated fat diet, UFD) and assessed changes in eWAT mitochondria. Compared to mice fed a LFD, SFD-fed mice have reduced mitochondrial biogenesis markers, mitochondrial fatty acid oxidation enzymes and TCA cycle enzymes, suggesting an impaired mitochondrial function that could contribute to increased fat mass. In contrast, isocaloric UFD-fed mice have increased expression of mitochondrial uncoupling protein 1 (UCP1) and peroxisomal fatty acid oxidation enzymes suggesting that elevated mitochondrial uncoupling and peroxisomal fatty acid oxidation could contribute to the reduction in fat mass. Interestingly, expression of UPRmt-associated proteins caseinolytic peptidase (ClpP) and heat shock protein 60 (Hsp60) are induced by UFD, whereas SFD reduced the expression of ClpP. Based on our data, we propose that induction of UPRmt helps to preserve a functional mitochondria and efficient utilization of fat by UFD whereas a dampened UPRmt response might impair mitochondrial function and promote fat accumulation by SFD. Thus, our findings suggest a potential role of UPRmt in mediating the beneficial effects of fish oil.

The purpose of this study was to establish reference intervals of the protein electrophoretic fractions and the acute-phase proteins hemoglobin binding protein (as determined by the haptoglobin assay) and C-reactive protein (CRP) and assess any possible correlations between varying age class, sex, location (Illinois or Michigan), year, or presence of snake fungal disease (SFD). Banked plasma samples were assayed from 130 eastern massasaugas from 2009 to 2014 in Illinois and Michigan. Snakes from Michigan had higher total protein (mean: 5.50 g/dl), albumin/globulin ratio (0.42), albumin (1.59 g/dl), and gamma globulins (0.55 g/dl) than from snakes in Illinois (4.72 g/dl, 0.29, 1.03 g/dl, 0.38 g/dl, respectively). Snakes in Illinois (22.19 g/ml) had higher CRP than snakes in Michigan (10.89 mg/ml). Adults had higher gamma globulins (0.47 g/dl) than juveniles (0.28 g/dl). Males had higher alpha-2 globulins (0.98 g/dl) and CRP (21.4 mg/ml) than females (0.85, 11.6, respectively). There were no significant differences in absolute plasma proteins in SFD-positive snakes, but the percentage of gamma globulins was significantly higher in positive snakes. Future research in this area can now build on this data to determine changes in population health over time or due to specific environmental or disease threats.

There is currently a lack of knowledge about the feasibility of performing procedures for fertility preservation after chemotherapy treatment has been initiated. In this experimental controlled study using adolescent mice, we aimed to investigate if the chance of rescuing and growing in vitro secondary follicles (SeF) would be affected three days after a single injection of cyclophosphamide (CPA). The main outcomes included were: 1) The number of SeF with good morphologic quality obtained per ovary 3 days after CPA injection, 2) SeF development in culture, 3) small follicle density (SFD) on histology, and 4) apoptosis markers, including terminal deoxynucleotidyl transferase dUTP nick end-labelling (TUNEL), mRNA expression, and distribution of p 53 upregulated modulator of apoptosis (Puma) and phosphatase and tensin homolog (Pten). We found a 60% reduction of SeF obtained per ovary in all CPA-treated groups vs. controls. However, in vitro survival rates at culture day 12 and antrum formation were similar among all groups. On histology, SFD was only significantly reduced in the high CPA dose group. Apoptotic cells were mainly found in large growing follicles of CPA groups. Our study indicates the feasibility of SeF isolation and in vitro follicle culture 3 days following CPA treatment and a still preserved SFD, particularly following a low-dose CPA treatment.

<AbstractText>Telemedicine in a school-based setting involving partnerships between an asthmatic child and health care provider can provide patients and caregivers with opportunities to better manage chronic conditions, communicate among partners, and collaborate for solutions in convenient locations.</AbstractText><AbstractText>This systematic review examines outcomes for asthmatic school-aged children involving asthma-based telemedical education.</AbstractText><AbstractText>Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched four databases with terms related to asthma, education and pediatrics. Included articles involved a school-based setting, children and adolescents, a telemedical mechanism for training, empirical study designs, and peer-review. We extracted data regarding a) participant background, b) research methods and purpose, and (c) outcomes.</AbstractText><AbstractText>408 papers were identified. Five met inclusion criteria. Three studies were randomized and two were cohort studies. In addition to clinical and educational outcomes, studies reported on satisfaction, self-management, asthma knowledge gain, and quality of life (QOL). We found support for caregiver/parent QOL and participant self-management behaviors. We also found mixed results for participant QOL. Clinical outcomes showed mixed support regarding airway inflammation improvement, medication use improvement, improvements in symptom burden and symptom-free days (<em>SFDs</em>), and spirometry improvements.</AbstractText><AbstractText>Results of real-time telemedically delivered asthma education to improve QOL, enhance symptom management ability, and reduce symptom burden were positive or non-significant. No study indicated negative effects due to telemedicine. Limited results indicate that patient education can, under certain circumstances, positively influence asthma burden. Further validation of intervention methods and tools as well as outcome measurement consistency is recommended.</AbstractText>

<p><div><b>PURPOSE</b></div>The goal of this work is to provide a large and consistent set of data for detector-specific output correction factors, <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> , for small static fields for seven solid-state detectors and to determine field output factors, <mml:math><mml:msubsup><mml:mi>Ω</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> , using EBT3 radiochromic films and W1 plastic scintillator as reference detectors on two different linear accelerators and four megavoltage photon beams. Consistent measurement conditions and recommendations given in the International Code of Practice TRS-483 for small-field dosimetry were followed throughout the study.</p><p><div><b>METHODS</b></div><mml:math><mml:msubsup><mml:mi>Ω</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> were determined on two linacs, Elekta Versa HD and Varian TrueBeam, for 6 and 10 MV beams with and without flattening filter and for nine fields ranging from 0.5 × 0.5 cm² to 10 × 10 cm² . Signal readings obtained with EBT3 radiochromic films and W1 plastic scintillator were fitted by an analytical function. Volume averaging correction factors, determined from two-dimensional (2D) dose matrices obtained with EBT3 films and fitted to bivariate Gaussian function, were used to correct measured signals. <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> were determined empirically for six diodes, IBA <em>SFD</em>, IBA Razor, PTW 60008 P, PTW 60012 E, PTW 60018 SRS, and SN EDGE, and a PTW 60019 microDiamond detector.</p><p><div><b>RESULTS</b></div>Field output factors and detector-specific <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> are presented in the form of analytical functions as well as in the form of discrete values. It is found that in general, for a given linac, small-field output factors need to be determined for every combination of beam energy and filtration (WFF or FFF) and field size as the differences between them can be statistically significant (P < 0.05). For different beam energies, the present data for <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> are found to differ significantly (P < 0.05) from the corresponding data published in TRS-483 mostly for the smallest fields (<1.5 cm). For the PTW microDiamond detector, statistically significant differences (P < 0.05) between <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> values were found for all investigated beams on an Elekta Versa HD linac for field sizes 0.5 × 0.5 cm² and 0.8 × 0.8 cm² . Significant differences in <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> between beams of a given energy but with and without flattening filters are found for measurements made in small fields (<1.5 cm) at a given linac. Differences in <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> are also found when measurements are made at different linacs using the same beam energy filtration combination; for the PTW microDiamond detector, these differences were found to be around 6% and were considered as significant.</p><p><div><b>CONCLUSIONS</b></div>Selection of two reference detectors, EBT3 films and W1 plastic scintillator, and use of an analytical function, is a novel approach for the determination of <mml:math><mml:msubsup><mml:mi>Ω</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> for small static fields in megavoltage photon beams. Large set of <mml:math><mml:msubsup><mml:mi>k</mml:mi><mml:mrow><mml:msub><mml:mi>Q</mml:mi><mml:mrow>clin</mml:mrow></mml:msub><mml:mo>,</mml:mo><mml:msub><mml:mi>Q</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow><mml:mrow><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>clin</mml:mrow></mml:msub></mml:mrow><mml:mo>,</mml:mo><mml:mrow><mml:mspace></mml:mspace><mml:msub><mml:mi>f</mml:mi><mml:mrow>ref</mml:mrow></mml:msub></mml:mrow></mml:mrow></mml:msubsup></mml:math> data for seven solid-state detectors and four beam energies determined on two linacs by a single group of researchers can be considered a valuable supplement to the literature and the TRS-483 dataset.</p>

In this study, we aimed to develop an experimental animal model for type 2 diabetes mellitus (T2DM) using a combination of monosodium glutamate (MSG) and high sucrose diet (HSD). Young male Wistar rats (20-30 g) were injected with MSG (2 or 4 mg/g, i.p. for 4 days). These rats were also fed an HSD, while the control group was fed a starch diet (SFD) for 150 days. Parameters assessed periodically were body weight, feed intake, blood glucose level, and oral glucose tolerance test (OGTT), lipid profile, liver and kidney function tests, skeletal muscle glucose uptake, cognitive function tests, and microvascular changes using isolated rat aorta. Histological changes in pancreas, liver, and kidney tissue were assessed using hematoxylin and eosin staining, whereas brain tissue was assessed using cresyl violet stain. Feeding MSG in combination with HSD in rats significantly increased body weight, and produced hyperglycemia, dyslipidemia, and hyperinsulinemia. Animals developed frank diabetic complications, which included insulin resistance in skeletal muscle, hypertension, vascular dysfunction, nephropathy, and dementia. Histological studies revealed neuronal loss with necrotic bodies in the brain, reduction in glomerular count in kidney, and severe hypertrophy and hyperplasia in the islets of Langerhans. These results indicate the successful induction of type-2 diabetes along with several diabetic complications by combining MSG with HSD.

Low birth weight infants are a heterogenous group of babies with medical risks that may vary according to gestational age. The degree of prematurity should be assessed using non-invasive valid methods. The purpose of this study was to assess the validity of four most commonly used methods for the assessment of gestational age in two groups of 60 appropriate for date pre-terms and 29 small for date babies. Our results support the use of prenatal assessment of gestational age by maternal history and early ultrasonography in afd-infants, the use of the examination of the anterior vascular capsule of the lens in afd and sfd infants and physical criteria rather than neurologic criteria when using the Ballard score.

OBJECTIVE

To evaluate the new commercial PTW-60019 synthetic single-crystal microDiamond detector (PTW, Freiburg, Germany) for relative dosimetry measurements on a clinical Leksell Gamma Knife Perfexion radiosurgery system.

METHODS

Detector output ratios (DORs) for 4 and 8 mm beams were measured using a microDiamond (PTW-60019), a stereotactic unshielded diode [IBA stereotactic field detector (SFD)], a shielded diode (IBA photon field detector), and GafChromic EBT3 films. Both parallel and transversal acquisition directions were considered for PTW-60019 measurements. Measured DORs were compared to the new output factor reference values for Gamma Knife Perfexion (0.814 and 0.900 for 4 and 8 mm, respectively). Profiles in the three directions were also measured for the 4 mm beam to evaluate full width at half maximum (FWHM) and penumbra and to compare them with the corresponding Leksell GammaPlan profiles.

RESULTS

FWHM and penumbra for PTW-60019 differed from the calculated values by less than 0.2 and 0.3 mm, for the parallel and transversal acquisitions, respectively. GafChromic films showed FWHM and penumbra within 0.1 mm. The output ratio obtained with the PTW-60019 for the 4 mm field was 1.6% greater in transverse direction compared to the nominal value. Comparable differences up to 0.8% and 1.0% for, respectively, GafChromic films and SFD were found.

CONCLUSIONS

The microDiamond PTW-60019 is a suitable detector for commissioning and routine use of Gamma Knife with good agreement of both DORs and profiles in the three directions.

OBJECTIVE

Single fetal demise (SFD) occurs in up to 20% of monochorionic pregnancies treated with laser coagulation for twin-twin transfusion syndrome (TTTS). We aimed to determine the independent factors associated with SFD to improve outcome in the care of TTTS pregnancies in the future.

METHODS

This was a case-control study on twin pregnancies treated for TTTS between 2007 and 2013. Data on ultrasound, laser surgery and outcome were retrieved from our monochorionic twin database. We analyzed separately cases of SFD in donor and recipient twins, and compared them with treated pregnancies that resulted in two live births.

RESULTS

Of the 273 TTTS pregnancies treated with laser coagulation, SFD occurred in 30 donors (11.0%) and 27 recipients (9.9%). In 67% of pregnancies with SFD, the death occurred within 1 week after laser treatment. For SFD in donors, absent/reversed end-diastolic flow in the umbilical artery was the strongest predictor (odds ratio (OR), 3.0 (95% CI, 1.1-8.0); P = 0.01), followed by the presence of an arterioarterial anastomosis (OR, 4.2 (95% CI, 1.4-13.1); P = 0.03) and discordance in estimated fetal weight (OR, 1.0 (95% CI, 1.0-1.1); P = 0.04). For SFD in recipients, independent predictors were absent/reversed A-wave in the ductus venosus (OR, 3.6 (95% CI, 1.2-10.5); P = 0.02) and the absence of recipient-to-donor arteriovenous anastomoses (OR, 10.6 (95% CI, 1.8-62.0); P < 0.01).

CONCLUSIONS

Our findings confirm earlier reports that suggest that abnormal blood flow is associated with SFD after laser treatment for TTTS. The association of SFD with the type of anastomoses is a new finding. We speculate that the type of anastomoses present determines the degree of hemodynamic change during laser therapy. Future strategies should aim at stabilizing fetal circulation before laser therapy to decrease the vulnerability to acute preload and afterload changes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVE

Results from previous studies suggest that past trauma experience increases the risk for medically unexplained somatic symptoms and somatoform disorders (SFD). This cross-sectional study examined the link between various lifetime traumas, idiopathic environmental intolerance (IEI), and SFD.

METHODS

Two clinical groups of 54 subjects with IEI and 44 subjects with SFD were compared to 54 subjects (comparison group, CG) free from both IEI and SFD regarding self-reported traumas. The subjects were mainly recruited via advertisements in local newspapers. From 970 individuals screened for IEI and multiple somatic symptoms, 152 were included through a two-step selection procedure consisting of screening questionnaires, a medical examination, and structured interviews for IEI and mental disorders.

RESULTS

In all three groups at least one potential traumatic event was reported rather frequently (CG: 70%; IEI: 82%; SFD: 73%). But contrary to our expectation, significant group differences were neither found in regard to the proportion of subjects with any trauma, nor traumas fulfilling DSM-IV criteria (CG: 41%; IEI: 48%; SFD: 59%), nor multiple traumas (CG: 43%, IEI: 56%, SFD: 39%). Only two trauma categories were endorsed more frequently by the two clinical groups than by the CG: the unspecified 'other' category (IEI, SFD)CG) and 'life-threatening illness' (IEI>CG).

CONCLUSIONS

No clear evidence was found for increased rates of trauma experience in IEI and SFD. However, the results of this exploratory study should be considered as preliminary. Comparing larger IEI and SFD groups with a representative population-based sample may yield different results.

OBJECTIVE

Diode detectors are commonly used in dosimetry, but have been reported to over-respond in small fields. Diode correction factors have been reported in the literature. The purpose of this study is to determine whether correction factors for a given diode type can be universally applied over a range of irradiation conditions including beams of different qualities.

METHODS

A mathematical relation of diode over-response as a function of the field size was developed using previously published experimental data in which diodes were compared to an air core scintillation dosimeter. Correction factors calculated from the mathematical relation were then compared those available in the literature.

RESULTS

The mathematical relation established between diode over-response and the field size was found to predict the measured diode correction factors for fields between 5 and 30 mm in width. The average deviation between measured and predicted over-response was 0.32% for IBA SFD and PTW Type E diodes. Diode over-response was found to be not strongly dependent on the type of linac, the method of collimation or the measurement depth.

CONCLUSIONS

The mathematical relation was found to agree with published diode correction factors derived from Monte Carlo simulations and measurements, indicating that correction factors are robust in their transportability between different radiation beams.

During studies on different aspects of fetal growth rate infants who were small-for-dates (SFD) large-for-dates (LFD) or within the normal range of birthweight for length of gestation (AFD) were examined within 48 h of birth. Gestational age was clinically assessed by the Dubowitz method. Among 140 AFD infants boys had higher mean values than girls for total and external scores, but there was no difference in neurological scores. Multiple regression of the score for external criteria on gestation, birthweight and sex, showed a significant contribution for birthweight and sex in addition to gestation; whereas gestation was the only singificant explanatory variable in the regression of the score for neurological criteria. When infants in the three weight groups were matched for length of gestation an sex, the SFD group had significantly lower mean total and external scores than the AFD group. The mean scores for the LFD group were not significantly higher than the AFD group. The neurological scores did not differ in the three groups. Maturation of external characteristics is related to weight as well as gestation. When assessment is made after birth by a clinical examination which includes these characteristics, the length of gestation of some SFD infants will be underestimated. The sex of the infant should also be borne in mind.

OBJECTIVE

To observe age- and sex-related differences in the complexity of the global and hemispheric white matter (WM) throughout adulthood by means of fractal dimension (FD).

METHODS

A box-counting algorithm was used to extract FD from the WM magnetic resonance images of 209 healthy adults from three structural layers, including general (gFD), skeleton (sFD), and boundaries (bFD). Model selection algorithms and statistical analyses, respectively, were used to examine the patterns and significance of the changes.

RESULTS

gFD and sFD showed inverse U-shape patterns with aging, with a slighter slope of increase from young to mid-age and a steeper decrease to the old. bFD was less affected by age. Sex differences were evident, specifically in gFD and sFD, with men showing higher FDs. Age × sex interaction was significant mainly in the hemispheric analysis, with men undergoing sharper age-related changes. After adjusting for the volume effect, age-related results remained approximately the same, but sex differences changed in most of the features, with women indicating higher values, specifically in the left hemisphere and boundaries. Right hemisphere was still more complex in men.

CONCLUSIONS

This study is the first that investigates the WM FD spanning adulthood, treating age both as a continuous and categorical variable. We found positive correlations between FD and volume, and our results show similarities with those investigating small-world properties of the brain networks, as well as those of functional complexity and WM integrity. These suggest that FD could yield a highly compact description of the structural changes and also might inform us about functional and cognitive variations.

The difficulty of measuring output factor (OPF) in a small field has been frequently discussed in recent publications. This study is aimed to determine the OPF in a small field using 10-MV photon beam and stereotactic conical collimator (cone). The OPF was measured by two diode detectors (SFD, EDGE detector) and one micro-ion chamber (PinPoint 3D chamber) in a water phantom. A Monte Carlo simulation using simplified detector model was performed to obtain the correction factor for the detector measurements. About 12% OPF difference was observed in the measurement at the smallest field (7.5 mm diameter) for EDGE detector and PinPoint 3D chamber. By applying the Monte Carlo-based correction factor to the measurement, the maximum discrepancy among the three detectors was reduced to within 3%. The results indicate that determination of OPF in a small field should be carefully performed. Especially, detector choice and appropriate correction factor application are very important in this regard.

We investigate the full functional form of the first passage time density (FPTD) of a tracer particle in a single-file diffusion (SFD) system whose population is: (i) homogeneous, i.e., all particles having the same diffusion constant and (ii) heterogeneous, with diffusion constants drawn from a heavy-tailed power-law distribution. In parallel, the full FPTD for fractional Brownian motion [fBm-defined by the Hurst parameter, H ∈ (0, 1)] is studied, of interest here as fBm and SFD systems belong to the same universality class. Extensive stochastic (non-Markovian) SFD and fBm simulations are performed and compared to two analytical Markovian techniques: the method of images approximation (MIA) and the Willemski-Fixman approximation (WFA). We find that the MIA cannot approximate well any temporal scale of the SFD FPTD. Our exact inversion of the Willemski-Fixman integral equation captures the long-time power-law exponent, when H ≥ 1/3, as predicted by Molchan [Commun. Math. Phys. 205, 97 (1999)] for fBm. When H < 1/3, which includes homogeneous SFD (H = 1/4), and heterogeneous SFD (H < 1/4), the WFA fails to agree with any temporal scale of the simulations and Molchan's long-time result. SFD systems are compared to their fBm counter parts; and in the homogeneous system both scaled FPTDs agree on all temporal scales including also, the result by Molchan, thus affirming that SFD and fBm dynamics belong to the same universality class. In the heterogeneous case SFD and fBm results for heterogeneity-averaged FPTDs agree in the asymptotic time limit. The non-averaged heterogeneous SFD systems display a lack of self-averaging. An exponential with a power-law argument, multiplied by a power-law pre-factor is shown to describe well the FPTD for all times for homogeneous SFD and sub-diffusive fBm systems.

Spray freeze-drying (SFD) process, which is a novel particle design technique previously developed by authors, has been improved by using four-fluid nozzle (4N) instead of conventional two-fluid nozzle (2N) to expand its application in pharmaceutical industry. Aqueous spray solutions of the drug and the polymeric carrier were separately supplied into 4N, and atomized while colliding with each other at the tip of nozzle. The droplets of mixed solutions were directly immersed into liquid nitrogen and immediately frozen to form a suspension. Then, the iced droplets were lyophilized by freeze-dryer to prepare the composite particles of the drug and carrier. This process has been used in the present study to modify and enhance the dissolution profiles of poorly water-soluble drug, phenytoin. Water-soluble and enteric polymeric carriers in pharmaceutical use were used as a dissolution modifier. The SFD composite particles prepared by using 4N were fully characterized compared to those using 2N from morphological and physicochemical perspectives. It was found that the particles have fine porous structure producing vast specific surface area. Further, phenytoin was completely dispersed as amorphous state in the polymeric matrix with higher carrier ratio than phenytoin:carrier = 1:3. The dissolution of phenytoin from the water-soluble carrier-based particles was greatly enhanced because of large effective surface area and disappearance of crystalline. On the other hand, the release profiles from enteric carrier-based particles showed the typical enteric patterns, that is, delayed in acidic medium and accelerated in neutral pH. The results demonstrated that SFD technique using 4N has potential to develop the novel solubilized formulation for poorly water-soluble APIs.

We investigate single file diffusion (SFD) of large particles entering a semi-infinite tube, such as luminal diffusion of proteins into microtubules or flagella. While single-file effects have no impact on the evolution of particle density, we report significant single-file effects for individually tracked tracer particle motion. Both exact and approximate ordering statistics of particles entering semi-infinite tubes agree well with our stochastic simulations. Considering initially empty semi-infinite tubes, with particles entering at one end starting from an initial time t = 0, tracked particles are initially super-diffusive after entering the system, but asymptotically diffusive at later times. For finite time intervals, the ratio of the net displacement of individual single-file particles to the average displacement of untracked particles is reduced at early times and enhanced at later times. When each particle is numbered, from the first to enter (n = 1) to the most recent (n = N), we find good scaling collapse of this distance ratio for all n. Experimental techniques that track individual particles, or local groups of particles, such as photo-activation or photobleaching of fluorescently tagged proteins, should be able to observe these single-file effects. However, biological phenomena that depend on local concentration, such as flagellar extension or luminal enzymatic activity, should not exhibit single-file effects.

238 small-for-dates (SFD), 246 average-for-dates (AFD) and 241 large-for-dates (LFD) infants were personally examined at birth, and measured thereafter in their own homes at the ages of 2, 6, 12 and 18 months, 2, 3 and 4 years. At each age weight, length or height, and head circumference measures in the SFD and LFD groups were distributed around the appropriate sex AFD mean values. In both extreme groups major shifts towards the mean occurred in the first six months for all three measures. From one year onwards only small within group fluctuations were seen. Correlations between one and four year values for weight, height and head circumference were high. At four years about 50% SFD children were within 1 S.D. of the mean, and 10% were still very small. Slightly more LFD children (55-60%) were near to the mean at this age, particularly for their head circumference values (70%), and only about 8% LFD children had very large heads. Trajectories of individual SFD and LFD children illustrate the great diversity of growth patterns within and between groups.

Snake fungal disease (SFD) is an emerging threat to snake populations in the United States. Fungal pathogens are often associated with a physiological stress response mediated by the hypothalamo-pituitary-adrenal axis (HPA), and afflicted individuals may incur steep coping costs. The severity of SFD can vary seasonally; however, little is known regarding (1) how SFD infection relates to HPA activity and (2) how seasonal shifts in environment, life history, or HPA activity may interact to drive seasonal patterns of infection severity and outcomes. To test the hypothesis that SFD is associated with increased HPA activity and to identify potential environmental or physiological drivers of seasonal infection, we monitored baseline corticosterone, SFD infection severity, foraging success, body condition, and reproductive status in a field-active population of pigmy rattlesnakes. Both plasma corticosterone and the severity of clinical signs of SFD peaked in the winter. Corticosterone levels were also elevated in the fall before the seasonal rise in SFD severity. Severely symptomatic snakes were in low body condition and had elevated corticosterone levels compared to moderately infected and uninfected snakes. The monthly mean severity of SFD in the population was negatively related to population-wide estimates of body condition and temperature measured in the precedent month and positively correlated with corticosterone levels measured in the precedent month. Symptomatic females were less likely to enter reproductive bouts compared to asymptomatic females. We propose the hypothesis that the seasonal interplay among environment, host energetics, and HPA activity initiates trade-offs in the fall that drive the increase in SFD prevalence, symptom severity, and decline in condition observed in the population through winter.

Ten populations of Xiphinema americanum-group nematodes were reared from individual females to evaluate inter- and intraspecific variation under identical host and environmental conditions. Data indicated that morphometric variability of X. americanum was the result of genetic variation rather than phenotypic plasticity and that genetic heterogeneity was greater than previously thought. Morphometrics of single female derived (SFD) populations identified different genotypes present in the field populations. Stylet length was the least variable morphometric character of SFD populations, but collectively stylet measurements of all individuals formed an uninterrupted continuum ranging from 107-148 mum. Range and frequency of stylet measurements of field populations could be accounted for by the relative proportion of different genotypes in the population. Nine SFD populations were identified as X. americanum sensu stricto, and one SFD population was similar to X. californicum.

BACKGROUND

The topographic mapping is useful for monitoring patients for the development of macular edema and following the resolution of edema after laser treatment.

OBJECTIVE

To evaluate the usefulness of optical coherence tomography (OCT) for mapping of macula after laser therapy in clinically significant macular edema (CSME).

METHODS

A prospective study was carried out enrolling 60 eyes of 35 patients with the diagnosis of CSME. OCT was performed at first visit and every successive follow up visit. The retinal thickness was measured automatically using OCT retinal mapping software.

METHODS

Correlation between vision status and central macular thickness (CMT) was done using the Spearman's correlation test. The analysis of variance (ANOVA) and independent t-test were used for comparison of groups.

RESULTS

The OCT revealed sponge like thickening pattern (ST) in 67.4 % followed by cystoid macular edema (CME) in 19.6 %. Best corrected visual acuity (BCVA) improved in 89.1 % after 6 months of treatment. There was high correlation between vision status and CMT (P =less than 0.001). The mean values of baseline CMT were 301.68 (+/-134.738), 434.83 (+/-180.758), 518.67 (+/- 275.184), 327 (+/-108.393) and 334.85 (+/- 158.91) microns for the OCT patterns of ST, CME, sub-foveal detachment (SFD), vitreo-macular interface abnormality (VMIA) and average CMT respectively (p=0.042).

CONCLUSIONS

OCT is a useful tool for evaluating CSME. It can show the various morphological variants of CSME while the BCVA and CMT are fairly different.

OBJECTIVE

To investigate the correlation between the 'smallest fluid depth' (SFD) measured on sonography (US) at the 'paracentesis pocket' with the amount of fluid drained in patients referred for US-guided large-volume paracentesis.

METHODS

US examinations performed to guide 60 paracenteses in 29 patients with large-volume ascites were reviewed and the SFD measured at the site of the paracentesis. The SFD was measured from the most superficial bowel loop to the abdominal wall. The SFD measurements were compared with the drained fluid volume (DFV) measurements.

RESULTS

The average DFV per paracentesis was 5.2 L with an average SFD measurement of 5.4 cm. For every 1-cm increase in the measured SFD, there was an average 1-L increase in the DFV. After applying this relationship to the measured depth in each case, the comparison between the estimated fluid volume (EFV) on US and the DFV demonstrated a <1-L difference in 38 of 60 paracenteses (63.3%) and a <2-L difference in 51 of 60 paracenteses (85%).

CONCLUSIONS

The SFD measured at the site of paracentesis shows a correlation with the drained fluid volume and can be used for fluid volume estimation on US.