Early Volume Research Articles

Low CSF β-amyloid levels predict early regional grey matter atrophy in multiple sclerosis

Background and purposeGrey matter (GM) atrophy is present from the earliest stages of multiple sclerosis (MS) and occurs largely in a nonrandom manner. However, the biological mechanisms underlying the progression of regional atrophy are still unclear. Aim of this study is to investigate whether amyloid pathology might be involved in determining the pattern of GM atrophy over time. MethodsForty-six subjects were recruited: 31 newly diagnosed relapsing-remitting (RR-) MS patients and 15 age- and sex-matched healthy controls (HC). Aβ levels were determined in CSF samples from all subjects. All participants underwent brain magnetic resonance imaging (MRI) at baseline, and 23 out of 31 patients at one year follow-up. T1-weighted scans were segmented using the Geodesic Information Flows software. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses. ResultsCSF Aβ concentration was the best predictor of global GM loss over time after age (β = 0.403; p = 0.024), in particular in the left precuneus (p = 0.045), in the left middle cingulate gyrus (p = 0.009), in the left precentral gyrus (p = 0.021) and in the right angular gyrus (p = 0.029). ConclusionsCSF Aβ levels seem to be crucial in MS early brain volume loss as GM atrophy manifests in regions particularly vulnerable to early Aβ deposition.

Proverbs: An Introduction and Commentary

Proverbs: An Introduction and Commentary

Anisotropic evolution of D-dimensional FRW spacetime

We examine the time evolution of the D=d+4 dimensional Einstein field equations subjected to a flat Robertson-Walker metric where the 3D and higher-dimensional scale factors are allowed to evolve at different rates. We find the exact solution to these equations for a single fluid component, which yields two limiting regimes offering the 3D scale factor as a function of the time. The fluid regime solution closely mimics that described by 4D FRW cosmology, offering a late-time behavior for the 3D scale factor after becoming valid in the early universe, and can give rise to a late-time accelerated expansion driven by vacuum energy. This is shown to be preceded by an earlier volume regime solution, which offers a very early-time epoch of accelerated expansion for a radiation-dominated universe for d=1. The time scales describing these phenomena, including the transition from volume to fluid regime, are shown to fall within a small fraction of the first second when the fundamental constants of the theory are aligned with the Planck time. This model potentially offers a higher-dimensional alternative to scalar-field inflationary theory and a consistent cosmological theory, yielding a unified description of early- and late-time accelerated expansions via a 5D spacetime scenario.

Case-management protocol for bloody diarrhea as a model to reduce the clinical impact of Shiga toxin-producing Escherichia coli infections. Experience from Southern Italy

To describe an operating protocol for bloody diarrhea (BD) in a pediatric population as a rapid response to a public health threat represented by an excess of pediatric HUS cases in the Apulia region (Southern Italy) starting from 2013. The protocol was set up with the goal of correct clinical management of Shiga toxin-producing Escherichia coli (STEC) infections, reductions in subsequent cases of hemolytic uremic syndrome (HUS), and improved short- and long-term disease outcomes. The protocol consisted of rapid hospitalization of children with bloody diarrhea (BD), hematochemical laboratory tests every 12–24 hours, and prompt laboratory diagnosis of STEC. No antibiotics were recommended until diagnosis. Children positive for STEC infections underwent early vigorous volume expansion. In June–December 2018, 438 children with BD were hospitalized, of which 53 (12.1%) had a STEC infection. The most common serogroups were O26 (36.1%), O111 (23.0%), and O157 (14.8%). Thirty-one samples carried the stx2 gene. Four cases evolved into HUS (7.5%), all with favorable outcome despite neurological involvement in two cases. Prompt and accurate laboratory diagnosis of STEC infections is of the utmost importance in patients with BD for correct clinical management. The strict adherence to the protocol could reduce the progression rate of STEC infections to HUS and prevents complications. Enhanced BD surveillance may help reduce cases of pediatric HUS in Southern Italy.

Normal reference values of three-dimensional speckle-tracking echocardiography-derived right atrial volumes and volume-based functional properties in healthy adults (Insights from the MAGYAR-Healthy Study).

The right atrium (RA) roles include being a systolic reservoir, an early diastolic conduit, and a late-diastolic booster pump. The present study aimed to assess normal reference values of three-dimensional speckle-tracking echocardiography (3DSTE)-derived RA volumetric data and volume-based functional properties in healthy adult subjects. We included 260 healthy adult subjects in sinus rhythm with complete clinical and demographic dataset, but excluded 110 of them because of inferior image quality. The remaining population sample comprised 150 subjects (31.0 ± 11.6 years, 79 males). Complete two-dimensional Doppler echocardiography and 3DSTE have been performed in all subjects. Systolic RA volumetric variables did not show changes over time, but after 50 years, a significant reduction could be demonstrated in RA stroke volume and emptying fraction. While early diastolic RA volume increased over time, RA stroke volume and emptying fraction decreased. While late-diastolic RA volume increased over age decades, similar increase could be detected in RA stroke volume but a reduction occurred in older ages. Late-diastolic RA emptying fraction showed an increasing (after the 40s)-decreasing (after the 50s) pattern. Our study provides normal reference values of 3DSTE-derived RA volumes and volume-based functional properties and their age- and gender dependency in healthy adult subjects.

COMP-13. EARLY TUMOR VOLUME EVOLUTION ADAPTIVELY PREDICTS PATIENT-SPECIFIC RESPONSE AND PROGRESSION RISK TO RADIOTHERAPY, PEMBROLIZUMAB, AND BEVACIZUMAB IN RECURRENT HIGH-GRADE GLIOMA IN A PHASE I TRIAL

Abstract PURPOSE/OBJECTIVES We set out to predict response and progression risk in recurrent high-grade glioma patients treated with hypofractionated stereotactic radiation plus pembrolizumab and bevacizumab (NCT02313272). At present RANO criteria define progression as 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement (either at baseline or best response) or significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids. To this extent, a predictive model is needed to adaptively learn and forecast individual response to therapy. We evaluate if early tumor volume evolution can train a mathematical model to predict subsequent response to therapy. MATERIALS/METHODS We develop a mathematical model that describes patient-uniform tumor growth rate and initial pembrolizumab and bevacizumab responses, and patient-specific treatment response dynamics. A total of 154 radiology scans were delineated to derive longitudinal tumor volumes of 26 patients. In a leave-one-out study, patient-uniform model parameters are derived and then applied to the left-out patient to adaptively learn treatment response dynamics to forecast tumor volume evolution and progression risk. Model prediction performance is evaluated based on classification accuracy, including sensitivity and specificity. RESULTS Patient-uniform glioma growth rate and initial treatment response rates are estimated to achieve acceptable fits to the longitudinal data of all untrained patients with R2 = 0.81 [0.75, 0.89]. Response dynamics are predicted with high accuracy (0.78 [0.76, 0.79]), with positive and negative predictive values of 0.90 [0.86, 0.92] and 0.81 [0.78, 0.86], and sensitivity and specificity of 0.71 [0.69, 0.73] and 0.88 [0.83, 0.91] respectively. CONCLUSIONS Two patient-specific parameters in a mathematical model can be adaptively learned from early tumor volume evolution to predict subsequent response to therapy and progression risk for individual patients. Future validation is required in an independent dataset and prospective evaluation in another clinical trial.

Evaluation of the Thermal and Shrinkage Stresses in Restrained High-Performance Concrete.

The early age volume deformation is the main course for the cracking of high-performance concrete (HPC). Hence, the shrinkage behavior and the restrained stress development of HPC under different restraints and curing conditions were experimentally studied in this paper. The method to separate the stress components in the total restraint stress was proposed. The total restrained stress was separated into autogenous shrinkage stress, drying shrinkage stress and thermal stress. The results showed that the developments of the free shrinkage (autogenous shrinkage and drying shrinkage) and the restrained stress were accelerated when the drying began; but the age when the drying began did not significantly influence the long-term shrinkage and restrained stress of HPC; the autogenous shrinkage stress continuously contributed to the development of the total restrained stress in HPC; the drying shrinkage stress developed very rapidly soon after the drying began; and the thermal stress was generated when the temperature dropped. The thermal stress was predominant at the early age, but the contributions of the three stresses to the total restrained stress were almost the same at the age of 56 d in this study.

H2FPEF Score for the Prediction of Exercise Intolerance and Abnormal Hemodynamics in Japanese - Evaluation by Exercise Stress Echocardiography Combined With Cardiopulmonary Exercise Testing.

Both the H2FPEF-score and nomogram-score, which consist of simple clinical parameters, can assist in diagnosing "early" heart failure with preserved ejection fraction (HFpEF) and only exertional dyspnea, but their these usefulness in Japanese remains unclear. We sought to investigate the correlation between these scores and exercise response, including the peak oxygen uptake (V̇O2), the pulmonary artery systolic pressure (PASP), the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') and stroke volume (SV) using exercise stress echocardiography (ESE) combined with cardiopulmonary exercise testing (CPET).Methods and Results:In this single-center, retrospective cross-sectional study the H2FPEF-score and nomogram-score were calculated in a total of 139 patients who underwent ESE combined with CPET. The scores correlated with peak V̇O2(r=-0.48, r=-0.44), PASP (r=0.23, r=0.29) and SV (r=-0.32, r=-0.19) at peak exercise. The nomogram-score correlated with E/e' (r=0.24). The prevalence of exercise intolerance (percent predicted peak V̇O2<75% and <50%) increased as the H2FPEF-score increased and reached 88.9% and 22.2% among the patients with high H2FPEF-score (6-9 points). The H2FPEF-score may be useful as the initial step to diagnosing 'early' HFpEF. The nomogram-score may be more useful in Japanese because of its more universal association with exercise response than the H2FPEF-score.

The assessment of wood utilization rate at UD. Karya Lomba Shipyard, Aceh Besar, Indonesia

This research aims to analyze the wood utilization rate at the manufacture of the vessel’s frames in UD. Karya Lomba shipyard, Lamteh Village, Peukan Bada subdistrict, Aceh Besar. The study was carried out in March to April 2018 by observing several parameters such as type of wood used, the process of vessel frames making and the utilization level of wood including initial wood volume, the volume of wood used and the volume of unused wood. The descriptive method was done by comparing the volume of wood used with the early wood volume and the volume of unused wood with wood scratch. Vessel’s frames from two under construction vessels were used as the study object by the length of 7.10 m, 13 frames and made from Jackfruit wood (Artocarpus heterophyllus). Then the length of the vessel II with 15.50 m, 35 frames and made from Laban wood (Vitex pubesceus). The results showed that the wood utilization rate for frames manufacturing on the ship I reached 38% and 60% of the vessel II reached 60% respectively.

Effective Contributor Communication and Editorial Process Efficacy

This is editorial for this issue, which discusses problems faced by scholar-led journals and contributor communications, and some of the steps taken to minimise them. It also includes a minor correction to an earlier volume along with highlights of the articles published in this issue of Exchanges. The editorial also includes details of the current calls for papers, both thematic and general ones, alongside acknowledgements and details on where to find out more information on contributing to Exchanges.

Early volume reduction of the hippocampus after whole-brain radiation therapy: an automated brain structure segmentation study.

To assess atrophy differences among brain regions and time-dependent changes after whole-brain radiation therapy (WBRT). Twenty patients with lung cancer who underwent both WBRT and chemotherapy (WBRT group) and 18 patients with lung cancer who underwent only chemotherapy (control group) were recruited. Three-dimensional T1WI were analyzed to calculate volume reduction ratio after WBRT in various brain structures. The volume reduction ratio of the hippocampus was compared among following 3 periods: 0-3, 4-7, and 8-11months after WBRT. The volume reduction ratio of the hippocampus was significantly higher in the WBRT group than in the control group (p < 0.05). In WBRT group, the volume reduction ratio of the hippocampus was significantly higher than that of the cortex and white matter (p < 0.05). There were significant differences in the volume reduction ratio between of 0-3months and that of 4-7months (p = 0.02) and between 4-7months and that of 8-11months (p = 0.01). The hippocampus is more vulnerable to the radiation compared with other brain regions and may become atrophic even in the early stage after WBRT.

P2459Do left atrial strain measurements provide information independent from left ventricular function parameters?

Abstract Introduction LA strain has been proposed to be a reliable and independent prognostic marker, as well as a useful surrogate of LA function. Purpose To assess if LA deformation measurements add independent information to standard echocardiographic measurements. Methods We included 66 normals and patients with a wide range of pathology and diastolic dysfunction grade from the echo data base of our hospital if image quality was sufficient for both LA and LV strain analysis. Patients with a mobile interatrial septum, arrhythmias and more than mild valvular regurgitation were not considered. Standard echocardiographic measurements including LA and LV volumes were performed according to current guidelines. LA and LV longitudinal strains were assessed by 2D speckle tracking in the same cardiac cycle in apical 4 and 2 chambers views using peak R as time reference. Peak LA and LV strain as well as LA and LV strain at onset of LA contraction were measured to calculate the strain components of all three phases of the cardiac cycle (systolic, early diastolic and late diastolic). Results In our cohort, the ratio of LA and LV systolic strain was directly and strongly related to the volume ratio of the two chambers (R2=0,894, slope=-1.001, p&lt;0.0001, see Figure 1). This was confirmed by a multivariate regression analysis, where systolic LA strain proved to be strongly dependent on systolic LV strain, LA volume and LV volume (R2=0.872, p&lt;0.0001 for the final model). For early diastolic strain, confounders were LV early diastolic strain, LA volume, LV volume and lateral wall E' tissue velocity (R2=0.784, p&lt;0.0001); while LA late diastolic strain was dependent on LV late diastolic strain, LA volume, LV volume and lateral wall A' tissue velocity (R2=0.823, p&lt;0.0001). Strain ratio vs volume ratio Conclusions Our data suggest that systolic LA strain (reservoir strain) is strictly dependent on systolic LV strain and the volume ratio of both chambers and, therefore, its measurement cannot provide additional information beyond classical measurements. Diastolic LA strain components show a less strict dependence on LV function and may therefore provide additional information.

Fast Start Advanced Calculus

Abstract This book continues the material in two early Fast Start calculus volumes to include multivariate calculus, sequences and series, and a variety of additional applications. These include pa...

The associations of early specialisation and sport volume with musculoskeletal injury in New Zealand children

ObjectiveTo investigate associations of early specialisation (highly specialised before age 13 years) and sport participation volume with injury history in New Zealand children. DesignCross-sectional survey study. MethodsChildren attending a national sports competition were invited to complete a questionnaire capturing specialisation level (high, moderate or low), participation volume and injury history. Multiple logistic regression was used to investigate associations between variables. ResultsNine hundred and fourteen children (538 female) completed the questionnaire. After adjusting for age, sex and hours of weekly sport participation, the odds of reporting an injury history were not significantly higher for early specialised children compared to children categorised as low specialisation (OR=0.88; CI=0.59–1.31; p=0.53). Participating in more hours of sport per week than age in years (OR=2.42; CI=1.27–4.62; p=0.02), playing one sport for more than 8 months of the year (OR=1.60; CI=1.07–2.36; p=0.02), or exceeding a 2:1 weekly ratio of organised sport to recreational free-play hours (OR=1.52; CI=1.08–2.15; p=0.02), increased the odds of reporting a ‘gradual onset injury’. ConclusionEarly specialisation in one sport did not increase the odds of reporting a history of injury. Exceeding currently recommended sport participation volumes was associated with increased odds of reporting a history of gradual onset injury.

Protestantism and liberty: Catharine Macaulay’s politics of religion as a response to David Hume

ABSTRACTCatharine Macaulay’s History of England from the Accession of James I (1763–1783) was intended by its author and received by its audience as, in part, a response to David Hume’s History of England. Macaulay’s writing has been read as a Whig counter to Hume’s Tory interpretation of England’s seventeenth-century history; more recent work has explored whether Macaulay or Hume has a better claim to be considered an “enlightenment historian”. This article will suggest that Macaulay’s views on the role of England’s Protestant belief and practice in the development and maintenance of the nation’s liberties contained, in the earlier volumes of her History, some of her substantive and important refutations of Hume’s arguments, and, further, that Macaulay’s well-argued claim that Protestantism was instrumental in the formation of England’s national character and potential enjoyment of political liberties was received by her readers as a particularly valuable part of her historical argument. Her accounts of Roman Catholic violence against Protestant victims at the Siege of La Rochelle and in the Irish Massacre of 1641 became some of the most quoted parts of her historical writing.

Windy Wyndham and the Wagon Who Couldn’t Swim by P. Gould

Gould, Peter. Windy Wyndham and the Wagon Who Couldn’t Swim. Bassendean, Western Australia, Peter Gould and Donna Franklin, 2018.&#x0D; This is the sixth volume in Peter Gould’s Stories from the Engine Shed series. These books tell the stories of the train engines and cars of the Bennett Brook Railway at Whiteman Park, near Perth in Western Australia. Apart from being a fun series of children’s books, this series is important because it demonstrates that the concept of anthropomorphized train cars is generic and does not belong to any particular franchise. The series has its own cast of characters and a unique Western Australian world in which they operate. While earlier volumes have been set in Whiteman Park, this is a story told by the large diesel locomotive, Windy Wyndham that harkens back to a time when Windy worked at the harbour in the northwestern Australian coastal town of Wyndham. &#x0D; The book is full of Donna Franklin’s brightly coloured pictures. The style of illustration varies significantly, even within pictures. Some of the images, particularly those with machines and people, are quite cartoonish. Drawings of people sometimes lack detail. However, when the subject is something in nature, Franklin’s work is stronger. Her rendition of a turtle, a crocodile, magpie-larks and seahorses are lovely. &#x0D; Each page is a picture with text overprinted. The text includes local references, such as the Freemantle Doctor, the cooling breeze that comes from the Indian Ocean. There are also some railway-specific words, such as “buffer beam”, “shunter”, and “cow catcher.” These words are explained in the glossary, “Ashley’s Railway Words”, at the end of the book. &#x0D; While not widely distributed, the series is available through the Bennett Brook Railway. This volume includes a loose single page insert that explains the history of the real Windy Wyndham engine, which has been at Whiteman Park since 1984. &#x0D; Overall, this is an excellent series, which is suitable for elementary school libraries and public libraries. &#x0D; Highly recommended: 4 out of 4 starsReviewer: Sandy Campbell&#x0D; Sandy is a Health Sciences Librarian at the University of Alberta, who has written hundreds of book reviews across many disciplines. Sandy thinks that sharing books with children is one of the greatest gifts anyone can give.

Cardiovascular Volume Reserve in Patients with Heart Failure and Reduced Ejection Fraction

Background Volume overload is a hallmark feature of HF. The pressure-based assessment of volume status has gained popularity in HF with the use of implantable devices, yet its accuracy to detect early intravascular volume expansion is unclear. Objectives To study the relationship between intravascular volume and intra-cardiac filling pressures in the setting of stable HFrEF. Methods 40 euvolemic HFrEF patients (10 subjects with a PAC), underwent intravascular volume expansion with 1 liter hydroxyl-ethyl-starch over 3 hours with coinciding intravascular volume measurements (technetium (99Tc)-labeled red blood cell technique). Results Intravascular blood volume increased from 5.0±1.0 L to 5.7±1.0 L (p Conclusion Euvolemic HFrEF patients can tolerate an intravascular volume expansion of 0.7L without signs and symptoms of HF. Due to this cardiovascular volume reserve, estimates of cardiac filling pressures might be of limited value to reliable assess intravascular volume changes.

Electronic Alberta Stroke Program Early CT score change and functional outcome in a drip-and-ship stroke service

BackgroundDebate continues as to whether patients with acute ischemic stroke with (suspected) large vessel occlusion benefit from direct referral versus secondary transportation.AimsTo analyze the change in early infarct signs, collaterals,...

SAT-168 PREVALENCE AND OUTCOMES OF ACUTE KIDNEY INJURY IN BURNS PATIENTS IN SOUTH AUSTRALIA

Acute kidney injury (AKI) in severely burned patients are associated with significance morbidity and mortality. Generally, the incidence of AKI is 30% with up to 80% mortality following severe burn. The causes of AKI in burn are multi factorial with notable difference between early and late AKI. Early identification and recognition of patients at risk are the key factors for the correct fluid and volume resuscitations. The Burns Unit will begin fluid resuscitation for burns of TBSA >15%. The aim of this study is to ascertain AKI prevalence and ultimately long term kidney functions in the burn population of TBSA >15%. This is a retrospective study recruited all patients with burns with TBSA >15% admitted to Burns Unit Royal Adelaide Hospital from 2009 to 2013. Exclusion criterion included TBSA < 15%, no documented TBSA and no serum creatinine during admissions or discharge. A total of 132 admissions following burn injury from 2009 till 2013 and severe burns were documented in 77 patients. 10 were excluded as there were missing serum creatinine results. The baseline characteristics are documented in Table 1. Prevalence of AKI among burn patients was as high at 61%.Tabled 1Table 1: Baseline characteristics of patients with severe burn patientsn (%), mean ± SDAKI (n= 41)No AKI (n=26)p-valueAge44.56 ±17.4744.42 ±16.130.969Male33 (80.5%)19 (73.1%)Co-morbiditiesDiabetesHypertensionCKD3 (7.3%)5 (12.2%)1 (2.4%)4 (15.4%)2 (7.7%)0 (0%)TBSA %39.07 ± 17.1027.13 ± 10.61< 0.05Serum creatinine on admission99.05 ± 28.5865.35 ± 15.99< 0.05Serum creatinine at discharge79.93 ± 78.7258.73 ± 15.310.101Days of Admission38.29 ± 39.1725.51 ± 32.950.156Hours in ICU(Days)211.46 ± 292.25(8.8 days)32.72 ± 90.64(1.4 days)< 0.05Mortality6 (0.15%)0 (0%) Open table in a new tab Among those who had AKI, 90.24% presented as early AKI. Mean creatinine at 5 years among available patients was 91.85 ± 50.51 mmol/L. Early surgical management and adequate volume resuscitations are important in acute severe burns patients to ensure good clinical outcome. Severe burn patients who suffered AKI had significantly higher serum creatinine on admission, larger TBSA as well as had to spend longer in ICU as compared to patients without AKI. The mortality rate was 0.15% and exclusively occurred among patients who had AKI.

Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial.

LBA2 Background: Testosterone suppression (TS) is the backbone of treatment for mHSPC. OS is improved by the addition of early docetaxel (DOC) or abiraterone to TS. ENZAMET assessed the effects of enzalutamide (ENZA), a potent androgen receptor (AR) inhibitor, versus a nonsteroidal anti-androgen (NSAA: bicalutamide, nilutamide, or flutamide) in addition to SOC (TS with or without DOC) in mHSPC. Methods: Men with mHSPC were randomly assigned 1:1 to receive TS plus either ENZA or NSAA. Randomization was stratified by: volume of disease (high vs low, according to CHAARTED); planned early DOC; planned anti-resorptive therapy, comorbidity score (ACE-27), and study site. The primary endpoint was overall survival. Accrual of 1100 men provided 80% power to detect a 25% reduction in the hazard of death (HR 0.75) with up to 4 interim analyses (IA), the first planned to occur after 235 deaths (50% of total information with a critical p-value threshold &lt;0.0031 by the Lan-DeMets alpha-spending approach with O’Brien-Fleming type shape). Subgroup analyses to assess possible modulation of the treatment effect were specified a priori and included planned early docetaxel (yes vs no) and volume of disease (high vs low). Results: We randomly assigned 1125 patients from 31MAR14 to 24MAR17. The treatment groups were well balanced for all important baseline factors. Criteria for early reporting were met at the first IA (28FEB2019) after a median follow-up of 33 months. Overall survival was prolonged by ENZA (see below). At 3 years, 36% NSAA vs 64% ENZA were still on their assigned study treatment. Serious adverse events (regardless of attribution) within 30 days of study treatment occurred in 42% ENZA vs 34% NSAA, commensurate with the different durations of study treatment. Conclusions: ENZA significantly improved OS when added to SOC in mHSPC. The benefits appeared lower in those planned to receive early DOC. Results of analyses with updated follow-up triggered by this IA will be presented. Clinical trial information: NCT02446405. [Table: see text]