Low MD Research Articles

Multi-objective optimisation and verification of creep-resistant Ni-base superalloy for electron-beam powder-bed-fusion

This paper reports the use of integrated computational alloy design, coupled with a rapid printability screening method, to downselect from a total of 70000 datasets in design space to five candidates in the first step, and then from five to one in the second step. The new Ni-base superalloy with compositions of Ni-5.03Al-2.69Co-5.63Cr-0.04Hf-1.91Mo-2.36Re-3.32Ta-0.57Ti-8.46W-0.05C-0.019B exhibits an optimal balance of density (8.82 g/cm2), printability (freezing range of 107 °C), thermal stability (γ′-volume fraction of 50.7% at 980 °C and low Md‾ value) and creep (rupture time of 612 h at 980 °C/120 MPa). The micro-hardness varies mildly from 417.2 ± 18.5 to 434.7 ± 14.6 HV, suggesting good phase stability. This is substantiated by microstructure observations, which revealed the absence of a topologically close-packed phase. Machine-learning tools of the artificial neural network (ANN), random forest, and support vector regression, respectively, were used to predict creep rupture time. The ANN algorithm achieves the highest accuracy in predicting creep life. By recognising the “black box” nature of the ANN, interpretability analysis was conducted using the local interpretable model-agnostic method. The analysis supports that the ANN model truly learned meaningful functional relationships, and thus is judged as reliable. Feature correlation evaluation outcome emphasises the importance of incorporating microstructure-related input features.

Microstructure white matter changes and serum GFAP among different phenotypes of multiple sclerosis

Background. Multiple sclerosis (MS) is an autoimmune disease that targets the central nervous system (CNS). A patient’s degree of demyelination and axonal degeneration can only be roughly estimated based on clinical symptoms, neurochemical analysis or standard clinical MRI. Magnetic resonance diffusion tensor imaging (DTI) may provide more information on MS pathology than T1- and T2-weighted MRI alone. Glial fibrillary acidic protein (GFAP) uniquely found in astrocytes in the (CNS), non-myelinating Schwann cells in the peripheral nervous system (PNS), and enteric glial cells. GFAP is postulated to be a biomarker of astrocytic damage and reactive astrogliosis. Methods. A total of 60 patients with MS was categorized into three equal groups according to The Multiple Sclerosis Progression Discussion Tool (MSProDiscuss tool): RRMS, SPMS, RRMS with high risk to become SPMS and 20 healthy controls. Baseline clinical characteristics and detailed medical and neurological history were taken into consideration, as well as time of onset of MS, delay in diagnosis, initial symptoms, relapses features and behavior, EDSS and disease modifying therapy. They were subjected to DTI-MRI and blood sampling for GFAP. Results. DTI was able to differentiate between different MS phenotypes and was able to detect progression when we evaluated DTI changes in NAWM in different brain areas as low FA and high MD were associated with progression and increasing disability (p value =0.001). Serum GFAP differs significantly between patients with SPMS or patients in transition, also, it was higher in patients in transition than RRMS or control group (P value <0.001). There was a significant correlation between serum GFAP and DTI changes in NAWM as higher titres of GFAP were associated with lower FA and higher MD values in NAWM of frontal, temporal lobes, and CC body. Conclusion. Serum GFAP in addition to DTI measurable microdamage in NAWM can give us a wide scope of view about potential progression in MS pathology and related astrocytopathy.

Developing Topics.

The novel diffusion-based Neurite Orientation and Dispersion Imaging (NODDI) model may provide complementary information to Diffusion Tensor Imaging (DTI) to increase sensitivity in characterizing tissue microarchitecture. We examined if one or a combination of both approaches can improve our understanding of at-risk tissue in and around white matter hyperintensities (WMH). From ADNI3, we identified individuals [n = 54, age = 78 ± 7, 46% F) with concurrent measures of multi-shell DTI, 3D FLAIR, and 3D MPRAGE. We segmented WMH from structural data using Lesion Segmentation Toolbox. We derived DTI (FA, MD) and NODDI parameters (NDI, ODI, Fiso) using QSIprep. We dilated up to 5 mm outside the WMH, applied an FA threshold of ≥ 0.2 to exclude gray matter, calculated DTI and NODDI parameters at 1 mm intervals within this region. We performed Pearson correlations between all parameters. Assuming normal white matter at 5 mm, we normalized these parameters with their respective values at 5 mm and plotted the spatial variation of each parameter in and outside the WMH. Normalized DTI and NODDI parameters representing spatial variations within the 5 mm region are shown in Fig 1A. Table 1 shows p-values comparing DTI and NODDI parameters between WMH the subsequent regions outside it. Compared to WMH, Fiso was significantly different at all distances. FA showed similar spatial characteristics with NDI and was negatively correlated with ODI. Fiso correlated very strongly with MD. In the WMHs and its immediate vicinity, low FA, NDI, ODI suggest lower cell density, while low Fiso and MD suggest low extracellular fluid volume. Together these observations may reflect cytotoxic edema, cell loss, and injury. Normal appearing white matter (3-5 mm) showed high FA, NDI, ODI, and low MD consistent with high cell density and normal extracellular water. In the transition between WMH vicinity and normal white matter, low FA, NDI, ODI, high MD and Fiso suggest cell loss only. This transition region could be at risk of converting to WMH. Future work will include longitudinal evaluation of WMH growth in the at-risk tissue. However, final validation of WMH pathology will need histological confirmation.

Importance of Pattern Standard Deviation of Humphrey 10-2 Visual Field to Evaluate Central Visual Function in Patients with Early-Stage Glaucoma.

To explore various parameters that can evaluate the central visual impairment in patients with early-stage glaucoma, we included patients into a study with central visual impairments with an MD value greater than -6.0 dB on the 24-2 VF test. A possible association between structural parameters acquired by OCT and functional parameters of VF and PERG was determined. A total of 70 eyes of patients with suspected glaucoma or NTG underwent VF, OCT, and PERG examinations. The patients were classified into two groups according to the MD of the 24-2 VF test. We used Pearson correlation analysis to evaluate the relationships between GCIPL thickness/RNFL thickness and visual functional parameters, such as PERG and perimetry. Linear regression analyses were conducted to evaluate the significant factors affecting the PSD of VF 10-2. In the low MD group, the P50 amplitude presented significant correlations (r = 0.346, p = 0.048) with GCIPL thickness. In the correlation analysis of the high MD group, it was found that only the PSD of 10-2 uniquely presented borderline significant correlations with GCIPL thickness (r = -0.327, p = 0.055), and no other functional parameter showed significant correlation. Univariate and multivariate analyses revealed that GCIPL thickness was significantly associated with a PSD of 10-2 VF (p < 0.001 and 0.013, respectively). Among various parameters, the P50 amplitude and 10-2 PSD demonstrated statistically borderline significant structure-function relationships with GCIPL thickness in early-stage glaucoma.

Overview of Suicide Risk in Elderly at Nursing Home of Jember

The risk of suicide is one of the most vulnerable nursing problems experienced by the elderly. The risk of suicide occurs because of several suicide risk factors experienced by the elderly. This study aims to describe the risk of suicide in the elderly at UPT PSTW (nursing home) Jember. The research design used is a descriptive survey. The sampling technique used is total sampling. The sample used in this study was 76 elderly who were selected based on inclusion and exclusion criteria. Data were collected using the Geriatric Suicide Ideation Scale (GSIS) questionnaire to determine the risk of suicide in the elderly. The One Sample Kolmogorov-Smirnov test was used to achieve the objectives of this study. The results showed that the elderly experienced a significant risk of suicide but in the low category Md (P25-75)= 62(60-65); Z=0.151; p-value=0.000. This study concludes that there is a significant risk of suicide in the elderly at UPT PSTW Jember. Therefore, it is necessary to increase the spirit of life for the elderly by always reminding the elderly that there is still life and hope for them.

Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study.

BackgroundPatients with end‐stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT).MethodsIn a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross‐sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross‐sectional area normalized for height2, reported in cm2/m2) and MD (mean attenuation of muscle cross‐sectional area, expressed in Hounsfield units). We determined age‐specific and sex‐specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival.ResultsAmong the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm2/m2 in men and 42.3 ± 7.3 cm2/m2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22–12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30–10.7, P = 0.015), and body mass index > 25 kg/m2 (aOR 2.94, 95% CI: 1.4–6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06–4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02–4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03–1.09, P = 0.0003). Low SMI was not associated with mortality.ConclusionsMyosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

LOW PERCENTAGE MOTILITY WHEN SPERM CONCENTRATION IS NORMAL DOES NOT APPEAR TO BE A CAUSE OF UNEXPLAINED FAILURE TO HAVE A LIVE DELIVERY DESPITE IN VITRO FERTILIZATION (IVF)

Some data suggest that sperm with very low motile density can lead to a trend for a lower chance of a live delivery following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) even despite the transfer of embryos with apparent normal morphology. The purpose of the present study was to see if low % motility in the presence of normal sperm concentration can also be a subtle cause of unexplained infertility. Couples were identified who were sharing donor oocytes when both male partners had normal concentrations of their sperm (≥20x106/mL) but where one had motility <30% and the other ≥50%. Subsequent fertilization rates, embryo quality, as evidence by number of blastomeres on day 3 transfer, and pregnancy rates were determined. ICSI was used or not according to the discretion of the physician. Tabled 1Pregnancy rates based on % motility for shared oocyte cycles when sperm concentration ≥20 mill/mLMotility<30%≥50%# cycles3737% fertilized70.5%70.1%% 6-8 cell day 360.6%70.7%% clinical pregnancy/transfer58.3%68.0%% miscarriage/clinical pregnancy live0.0%35.3%% delivered58.3%44.0%% implantation31.3%40.0% Open table in a new tab There were no statistical differences or trends that would suggest that low % motile sperm, despite normal sperm concentration, leads to embryos with a lower chance to achieve a live delivery. With no trends seen at all, the study will not be continued. Based on other studies, there is a suggestion that sperm from men with very low motile density, used for IVF-ET, the embryos formed, though appearing to be morphologically normal, may be the cause of lower live delivered pregnancy rates. This raised the question as to the possibility that sperm with very low MD may be more likely to have chromosome defects. That data was also based on similar evaluation of matched pairs sharing one pool of oocytes, thus ruling out an oocyte factor. It does not seem that low percentage of sperm motility is a subtle cause of unexplained infertility when sperm concentration was normal based on this pilot study.

Mammographic density as marker of increased risk of breast cancer

‘Mammographic density’ (MD) is a concept that has entered medical practice since 2017. as a marker of breast cancer risk factor (BC) according to the international classifiation of NCCN. The term reflcts the degree of severity of benign diffuse breast dysplasia in women of post-reproductive age. MD is determined by the ratio of stromal, epithelial, and adipose tissue. According to the literature, in young women, high MD limits the possibilities of X-ray mammography, reducing its effectiveness in oncomammoscreening, leading to the detection of advanced forms of breast cancer. Post-reproductive women with high MD are more likely to develop breast cancer than those with low MD. In this regard, MD is of particular interest for studying its role in oncogenesis. Recent molecular genetic studies of the differences between high and low MD explain the main biological reasons why post-reproductive women with dense breast structure are at a higher risk of developing breast cancer. The aim is to identify the factors that inflence the relationship of MD with the risk of developing breast cancer based on a comparative analysis of molecular genetic studies and radiological manifestations of MD of different severity and to identify the factors that contribute to the formation of MD variants.

SPERM WITH VERY LOW MOTILE DENSITY (MD) MAY BE A CAUSE OF REDUCED CHANCE OF LIVE DELIVERY DESPITE TRANSFER OF NORMAL MORPHOLOGIC EMBRYOS

To determine if a male factor, specifically low MD, can reduce the chance of a live baby despite normal fertilization and the production of embryos with good morphology. Prospective comparison study. To eliminate an oocyte factor as a confounding variable, the study selected pairs of patients sharing donor oocytes. The only couples selected were those where the male partners of 1 couple had a MD below <10x106/mL and the other male partner ≥10x106/mL. The low MD group when evaluating outcome was further divided into very low MD of <5x106/mL and 5-9.9x106/mL. Only cycles where both couples had a fresh embryo transfer (ET) on day 3 were included. Intracytoplasmic sperm injection (ICSI) was used for couples where MD was <10x106/mL unless strict morphology was ≤4% when ICSI was used even with normal MD. There were 242 ETs in low MD groups and 245 in normal MD group.Tabled 1Comparison of in vitro fertilization (IVF) outcome according to MD in pairs sharing oocytesMotile Density (10x106/mL)<55-9.9≥10# transfers14399245% fertilized72.1%70.9%70.9%% 6-8 cell day 357.3%60.2%62.4%% clinical preg./transfer47.6%49.5%56.3%% miscarriage/clinical preg. live20.6%8.2%16.7%% delivered37.8%45.5%46.9%% implantation26.5%26.7%30.9%Chi-square = NS. Power analysis showed one would need to triple the number of subjects to show that the difference in live delivery rates comparing very low MD vs. normal MD was significant. Evaluating a subset with normal morphology using strict criteria, the live delivered pregnancy rate for very low MD was 36.1% (26/72) vs. 48.3% and miscarriage rate was 29.7% vs. 13.3%. Thus, low strict morphology was not a confounding variable. Since both low MD groups had ICSI performed, and the less severe group did as well as the normal MD group, ICSI did not seem to be a confounding variable. There was an average of 1.8 embryos transferred in the very low MD group vs. 1.9 in the normal MD group. Open table in a new tab Chi-square = NS. Power analysis showed one would need to triple the number of subjects to show that the difference in live delivery rates comparing very low MD vs. normal MD was significant. Evaluating a subset with normal morphology using strict criteria, the live delivered pregnancy rate for very low MD was 36.1% (26/72) vs. 48.3% and miscarriage rate was 29.7% vs. 13.3%. Thus, low strict morphology was not a confounding variable. Since both low MD groups had ICSI performed, and the less severe group did as well as the normal MD group, ICSI did not seem to be a confounding variable. There was an average of 1.8 embryos transferred in the very low MD group vs. 1.9 in the normal MD group. Though the differences were not significant, possibly the results could suggest that even using the best quality oocytes, males with very low MD may be responsible for unexplained failure to achieve a live birth even with the transfer of normal quality embryos by morphologic criteria. Since good oocytes can sometimes correct sperm defects, it may be that these differences may be even greater if the oocytes retrieved are of less quality. Thus, in cases of repeated failure to achieve live deliveries in couples where the sperm has very low MD, instead of switching to donor oocytes, one could consider first trying donor sperm. A larger possibly multicenter study is needed to support or refute this suggested cause of unexplained infertility.

Dust mass and dust production efficiencies on the redshift frontier

AbstractIn order to clarify the dust production in the early Universe, we constrain the dust mass in high-redshift (z ≳ 5) galaxies using the upper limits obtained by ALMA. We perform fitting to the rest-frame UV–far-infrared spectral energy distribution (SED) of a giant Lyα emitter, Himiko, at z = 6.6 and a composite SED of z &gt; 5 Lyman break galaxies (LBGs). For Himiko, we obtain a high dust temperature &gt; 70 K. This high dust temperature puts a strong upper limit on the total dust mass Md ≲ 2 × 106 M⊙, and the dust mass produced per supernova (SN) md,SN ≲ 0.1 M⊙. Such a low md,SN suggests significant loss of dust by reverse shock destruction or outflow. For the LBG sample, we only obtain an upper limit for md,SN as ∼2 M⊙. This clarifies the importance of observing UV-bright objects (like Himiko) to constrain the dust production by SNe.

The Need for Holism in the Art and Science of Medicine: A Clinical Conversation with Tieraona Low Dog, MD, and Robert Rountree, MD

The Need for Holism in the Art and Science of Medicine: A Clinical Conversation with Tieraona Low Dog, MD, and Robert Rountree, MD

Oral Versus Transdermal Estrogen In Turner Syndrome: A Systematic Review And Meta-Analysis

To conduct a systematic review and meta-analysis comparing transdermal estrogens (TDEs) versus oral estrogens (OEs) in Turner syndrome (TS). Randomized trials and observational comparative studies with a minimal follow-up of 6 months for skeletal and metabolic outcomes and serum hormone changes were included. Outcomes were pooled with a random effects model and are reported as mean differences between OE and TDE groups and 95% confidence intervals (CIs). Of 845 candidate references, 4 studies were included. Both OEs and TDEs were associated with an increase in whole-body bone mineral density (BMD) z-score, with TDE therapy displaying a greater increase. OEs were associated with higher fasting glucose and total cholesterol. Both OEs and TDEs reduced low-density lipo-protein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C), with OEs providing a more favorable effect. The use of 17-β estradiol was associated with a higher total cholesterol and lower LDL-C than TDE. No statistically significant difference was found between OEs and TDEs in body mass index, fat mass, fat free mass, insulin-like growth factor 1, insulin-like growth factor binding protein 3, fasting insulin, triglycerides, estradiol, or estrone levels. In girls with TS, TDEs may be associated with a more beneficial effect on fasting glucose, cholesterol, and whole-body BMD. However, OEs have a more favorable impact on LDL-C and HDL-C. 17-β estradiol has a more favorable effect on LDL-C. BMI = body mass index BMD = bone mineral density CI = confidence interval HDL-C = high density lipo-protein-cholesterol IGF-1 = insulin-like growth factor 1 IGF-BP3 = insulin-like growth factor binding protein 3 LDL-C = low density lipoprotein-cholesterol MD = mean difference OE = oral estrogen RCT = randomized controlled trial TDE = transdermal estrogen TS = Turner syndrome.

Prevalence of sarcopenia and predictors of body composition among women with early-stage breast cancer.

160 Background: Body mass index (BMI) does not accurately reflect body composition, particularly among cancer survivors. Sarcopenia (low skeletal muscle mass) and low muscle radio-density (MD; suggesting fat infiltration into muscle, compromising function) increase risk of surgical complications and chemotherapy toxicity and are associated with worse survival in advanced cancer. Little is known about the prevalence or predictors of sarcopenia and low MD in early-stage breast cancer. Methods: We studied 2,914 Kaiser Permanente members diagnosed with Stage I-III breast cancer from 2005-2013. Using computed tomography (CT) scans of the third lumbar vertebra from clinical care, we determined sarcopenia (skeletal muscle index &lt; 41 muscle [cm2]/height [m2]) and low MD ( &lt; 25-Hounsfield Units for non-obese; &lt; 33 for obese) using published cut points. We assessed associations with characteristics including age, race, BMI, age, stage, lifestyle and co-morbidities with logistic regression. We also examined moderate/vigorous physical activity among a subset of 672 women with activity questionnaires. Results: At diagnosis, mean age was 56 years and time to CT was 1 month. Both sarcopenia and low MD were common among early-stage breast cancer survivors (40% and 38% respectively). In multivariate analyses, the odds of sarcopenia and low MD increased with age (per 5 years, Odds Ratio [OR] 95% Confidence Interval [CI] of OR = 1.33; 95%CI: 1.27, 1.39 and OR = 1.41; 95%CI: 1.35, 1.47 respectively). The odds of sarcopenia decreased with greater BMI (OR = 0.80; 95%CI: 0.78, 0.82 per kg/m2), while the odds of low MD increased (OR = 1.03; 95%CI: 1.01, 1.04 per kg/m2). Black race was associated with lower odds of sarcopenia and low MD, while physical activity levels were associated with lower odds of sarcopenia and more favorable MD. Conclusions: Sarcopenia and low MD are highly prevalent among breast cancer survivors. While older age is strongly associated with these conditions, they occur across ages and stages. Differences in body composition by race and age may underlie differences in the association of BMI with cancer outcomes; understanding these may help guide clinical interventions.

Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study.

Background and purposeMemory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first occurrence of structural damage and are preceded by microscopic changes that may already be associated with a worse memory function. We therefore examined the relationship between hippocampal integrity, volume, and memory performance long after first-ever ischemic stroke in young adults.MethodsWe included all consecutive first-ever ischemic stroke patients, without hippocampal strokes or recurrent stroke/TIA, aged 18–50 years, admitted to our academic hospital between 1980 and 2010. One hundred and forty-six patients underwent T1 MPRAGE, DTI scanning and completed the Rey Auditory Verbal Learning Test and were compared with 84 stroke-free controls. After manual correction of hippocampal automatic segmentation, we calculated mean hippocampal fractional anisotropy (FA) and diffusivity (MD).ResultsOn average 10 years after ischemic stroke, lesion volume was associated with lower ipsilateral hippocampal integrity (p<0.05), independent of hippocampal volume. In patients with a normal ipsilateral hippocampal volume (volume is less than or equal to 1.5 SD below the mean volume of controls) significant differences in ipsilateral hippocampal MD were observed (p<0.0001). However, patients with a normal hippocampal volume and high hippocampal MD did not show a worse memory performance compared with patients with a normal volume and low hippocampal MD (p>0.05).ConclusionsPatients with average ipsilateral hippocampal volume could already have lower ipsilateral hippocampal integrity, although at present with no attendant worse memory performance compared with patients with high hippocampal integrity. Longitudinal studies are needed to investigate whether a low hippocampal integrity after stroke might lead to exacerbated memory decline with increasing age.

Pelvic floor muscle electromyography during different running speeds: an exploratory and reliability study.

Stress urinary incontinence (SUI) affects women of all ages including young athletes, especially those involved in high-impact sports. To date, hardly any studies are available testing pelvic floor muscles (PFM) during sports activities. The aim of this study was the description and reliability test of six PFM electromyography (EMG) variables during three different running speeds. The secondary objective was to evaluate whether there was a speed-dependent difference between the PFM activity variables. This trial was designed as an exploratory and reliability study including ten young healthy female subjects to characterize PFM pre-activity and reflex activity during running at 7, 9 and 11 km/h. Six variables for each running speed, averaged over ten steps per subject, were presented descriptively, tested regarding their reliability (Friedman, ICC, SEM, MD) and speed difference (Friedman). PFM EMG variables varied between 67.6 and 106.1 %EMG, showed no systematic error and were low for SEM and MD using the single value model. Applying the average model over ten steps, ICC (3,k) were >0.75 and SEM and MD about 50 % lower than for the single value model. Activity was found to be highest in 11 km/h. EMG variables showed excellent ICC and very low SEM and MD. Further studies should investigate inter-session reliability and PFM reactivity patterns of SUI patients using the average over ten steps for each variable as it showed very high ICC and very low SEM and MD. Subsequently, longer running distances and other high-impact sports disciplines could be studied.

Effects of socket alignment perturbations on the muscle activity and comfort of unilateral transfemoral amputees during level surface ambulation

88.4%EMG. Only running at 11 km/h leads to higher values rising up to 106.1%EMG. PFM EMG variables showed no systematic error (Friedman). They were low for SEM and MD, and ICC(3,1) were 0.75 and SEM (1.9–2.5%EMG for 7 km/h, 1.9–2.4%EMG for 9 km/h, 2.1–2.9%EMG for 11 km/h) and MD (5.2–7.0%EMG for 7 km/h, 5.4–6.6%EMG for 9 km/h, 5.9–8.0%EMG for 11 km/h) about 50% lower than for the single value model. Conclusion(s): The higher values of the variables during running at 11 km/h compared to the slower running speeds of 7 and 9 km/h could be the response to the higher ground reaction forces and therefore higher impacts causing higher PFM pre-activity and reflexivity during the fast running speed of 11 km/h. This study found excellent intra-session ICC(3,k) and very low SEM and MD of PFM EMG variables of preactivation and reflexive function during running. However, the results should be interpreted with caution, as – in consideration of crosstalk it is possible that not only PFM EMG was recorded but intravaginal EMG, meaning the sum of all muscle activity within the vagina during running. Consequently, crosstalk during functional whole body movements should be subject to further investigations of PFM EMG. Implications: Further trials should study inter-session reliability and PFM reactivity patterns of SUI patients using the average over ten steps for each variable as it showed very high ICC and very low SEM and MD. Subsequently longer running distances and other high-impact sports disciplines would be of high interest.

Abstract P4-04-11: Comparing tissue compositions of within-individual mammographically high and low dense breast tissue

Abstract Abstract Purpose Mammographic density (MD) refers to the extent of radio-opaque breast tissue on a mammogram. Adjusted for a women’s age and body mass index (BMI), it is a strong and independent risk factor for breast cancer (BC). The presentation of mammographically dense breast is not uncommon in the normal female population, and patients’ awareness of its association with BC risk has been growing following mandatory reporting of MD by physicians in several states of America. Women with breasts that have over 75% dense tissue are 4 to 6 times more likely to develop BC than women with breasts that have less than 10% dense tissue. However, the biological basis of how high MD raises BC risk remains elusive. We aimed to examine the histological and molecular differences between high and low dense breast tissues of healthy women, using specimens accrued from prophylactic mastectomy procedures. Method 48 women between 2008 and 2013 underwent prophylactic mastectomy at St Vincent’s Hospital and Peter MacCallum Cancer Centre due to a high BC risk profile. Of these, 41 were eligible for analyses. Tissue slice resected from the mastectomy specimen was X-rayed, and high (HD) and low dense (LD) regions were dissected based on the radiological appearance. The histological composition, immunohistochemistry and proliferation status were assessed on matched high and low MD tissue of the same breast. Signed rank test and paired t test were used for quantitative analyses of potential differences between HD and LD tissue. Result HD tissue demonstrated a significantly greater proportion of stroma (p&amp;lt;0.0001) and epithelium (p&amp;lt;0.0001), and less amount of fat (p&amp;lt;0.0001) than LD tissue (n=41 women). Epithelium from HD region also demonstrated epithelial-mesenchymal transition (EMT) plasticity, which was evident as the co-expression of cytokeratin (CK)-19 and vimentin in the glandular area. There was no significant difference with regards to oestrogen receptor (ER) (p= 0.2772), progesterone receptor (PR) (p= 0.9910), and Ki-67 (p= 0.6028) expression between HD and LD tissue. Conclusion and Significance We found that increased stroma and epithelium proportions contribute to the dense appearance on mammogram. Moreover, dense tissue did not demonstrate differed hormonal receptor expression or proliferation status from non-dense tissue, but showed a preponderance of EMT in the form of co-localisation by both CK-19 and vimentin in some of the epithelial cells. Our study is the first to report EMT phenomenon in benign mammary tissue, and suggests that investigations of the stromal micro-environment, and their interactions with epithelium may be key to improving our understanding on MD-mediated BC risk. Citation Format: Cecilia W Huo, Dexing Huang, Grace L Chew, Prue Hill, Wendy V Ingman, Michael Henderson, Kara L Britt, Rik Thompson. Comparing tissue compositions of within-individual mammographically high and low dense breast tissue [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-04-11.

White matter microstructure abnormalities in pediatric migraine patients.

Diffusion tensor (DT) magnetic resonance imaging (MRI) provides several quantities with the potential to disclose white matter (WM) microstructural abnormalities. We explored alterations of WM architecture in pediatric migraine patients using DT MRI and two different methods of analysis. Dual-echo and DT MRI scans were acquired from 15 pediatric migraine patients and 15 age-matched controls. Whole-brain voxel-wise comparisons of WM DT MRI abnormalities were performed using tract-based-spatial-statistics (TBSS). A DT probabilistic tractography analysis was also run. Both TBSS and DT tractography analysis showed that, compared to controls, pediatric migraine patients had significant lower mean (MD), axial (AD) and radial (RD) diffusivity of WM tracts located in the brainstem, thalamus and fronto-temporo-occipital lobes, bilaterally. Patients also experienced increased fractional anisotropy (FA) of the optic radiations. No correlation was found between WM tract abnormalities and disease duration and attack frequency. Pediatric migraine patients harbor diffuse brain WM microstructural abnormalities. High FA and low MD, AD and RD in these patients might be explained by repeated neuronal activation, which may lead to cell swelling and stimulate activity-dependent myelin-modulation, or by increased fiber and dendritic densities. Both these mechanisms might reflect a hyperexcitability of the brain in migraineurs.

Mid- to late-Holocene East Asian summer monsoon variability recorded in lacustrine sediments from Jingpo Lake, Northeastern China

The Northeastern China involves complex interactions between the East Asian summer monsoon (EASM) circulation and the polar climate system, and plays a significant role as the bridge communicating low- and high-latitude climatic processes. High-resolution multi-proxy analysis of a robust accelerator mass spectrometry (AMS) 14C dated lacustrine sediment core recovered from Jingpo Lake in Northeastern China provides a detailed history of EASM variability and vegetation changes since ~5100 cal. yr BP. The period from ~5100 to 3600 cal. yr BP was characterized by the highest pollen percentages of Quercus, Ulmus, Juglans and Corylopsis; low Md (median grain size diameter); and high δ13Corg values, reflecting a relatively warm and humid period. The period between ~3600 and 2100 cal. yr BP is characterized by high Md and low δ13Corg values, and a rapid increase in pollen percentages of herbs, indicating cool and dry climatic conditions. From ~2100 to 150 cal. yr BP, a gradual increase in δ13Corg values and low Md values, and a rapid increase in Carpinus, Juglans and Corylopsis pollen percentages was observed, indicating climate change towards warmer and wetter conditions. After ~150 cal. yr BP, the highest values of total organic carbon mass accumulation rate (TOC-MAR), total nitrogen mass accumulation rate (TN-MAR) and magnetic susceptibility suggesting that the Jingpo Lake region has been severely affected by human activities. The EASM variability in Northeastern China during the mid- to late Holocene shows trends similar to EASM records in China. Furthermore, our findings indicate that the variability of the EASM during the mid- to late Holocene on the multi-decadal to centennial scale was forced by changes in both solar output and oceanic–atmospheric circulation interaction.

White matter abnormalities associated with military PTSD in the context of blast TBI

Mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common among recent military veterans and involve substantial symptom overlap, making clinical distinction and effective intervention difficult. Emerging evidence of cerebral white matter abnormalities associated with mTBI may provide a biological measure to inform diagnosis and treatment, but the potentially confounding effects between PTSD and mTBI have largely gone unexamined. We collected diffusion imaging data from 133 recently-deployed American service members who developed PTSD and/or sustained mTBI, or had neither condition. Effects of PTSD and mTBI on traditional tensor-based measures of cerebral white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) were compared in anatomical regions of interest and individual voxels throughout the brain. Generalized FA (GFA), which allows for multiple fiber orientations per voxel, was also included to improve sensitivity in white matter areas containing crossing or diverging axon bundles. PTSD was consistently associated with high GFA in select brain regions, greater likelihood of regions and voxels with abnormally low MD, and a greater number of voxels with abnormally high FA, while mTBI was associated with fewer high MD regions. Overall, PTSD was associated with more restricted diffusion (low MD) and greater anisotropy (high GFA) in regions of crossing/diverging fibers poorly characterized by a single tensor (FA), suggesting that interstitial fibers may be involved. Contrary to earlier results in a sample without PTSD, mTBI was not associated with anisotropy abnormalities, perhaps indicating the cooccurrence of PTSD and mTBI requires special consideration with regard to structural brain connectivity.