Definite Progress Research Articles

Acute encephalitis in children: Progress and priorities from an Australasian perspective.

Encephalitis is a complex neurological syndrome caused by inflammation of the brain that occurs with highest incidence in children. It is challenging to diagnose and manage due to the variety of aetiologies and non-specific clinical presentations. We discuss the recent progress in clinical case definitions; review recent, large, prospective epidemiological studies; and describe aetiologies. We emphasise infectious causes relevant to children in Australasia but also consider emerging immune-mediated syndromes responsive to immune therapies. We identify priorities for future research in children, given the potential for climate change and international travel to influence the emergence of infectious agents in our region.

Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS.

Definite progress has been made in the exploration of myelodysplastic syndromes (MDS) by flow cytometry (FCM) since the publication of the World Health Organization 2008 classification of myeloid neoplasms. An international working party initiated within the European LeukemiaNet and extended to include members from Australia, Canada, Japan, Taiwan and the United States has, through several workshops, developed and subsequently published consensus recommendations. The latter deal with preanalytical precautions, and propose small and large panels, which allow evaluating immunophenotypic anomalies and calculating myelodysplasia scores. The current paper provides guidelines that strongly recommend the integration of FCM data with other diagnostic tools in the diagnostic work-up of MDS.

THU0106 Fat Metaplasia in the Sacroiliac Joints on MRI is Associated with Radiographic Status and Progression in the Spine of Patients with Axial Spondyloarthritis

BackgroundFat metaplasia in the sacroiliac joints (SIJ) may be an early manifestation of axial SpA. It has been shown to follow resolution of bone marrow edema and treatment group differences...

Towards an accurate model of redshift-space distortions: a bivariate Gaussian description for the galaxy pairwise velocity distributions

AbstractAs a step towards a more accurate modelling of redshift-space distortions (RSD) in galaxy surveys, we develop a general description of the probability distribution function of galaxy pairwise velocities within the framework of the so-called streaming model. For a given galaxy separation , such function can be described as a superposition of virtually infinite local distributions. We characterize these in terms of their moments and then consider the specific case in which they are Gaussian functions, each with its own mean μ and variance σ2. Based on physical considerations, we make the further crucial assumption that these two parameters are in turn distributed according to a bivariate Gaussian, with its own mean and covariance matrix. Tests using numerical simulations explicitly show that with this compact description one can correctly model redshift-space distorsions on all scales, fully capturing the overall linear and nonlinear dynamics of the galaxy flow at different separations. In particular, we naturally obtain Gaussian/exponential, skewed/unskewed distribution functions, depending on separation as observed in simulations and data. Also, the recently proposed single-Gaussian description of redshift-space distortions is included in this model as a limiting case, when the bivariate Gaussian is collapsed to a two-dimensional Dirac delta function. More work is needed, but these results indicate a very promising path to make definitive progress in our program to improve RSD estimators.

Sustainable development in seaports: a multi-case study

Seaports are a vital part of the maritime transport industry and have a key role in integrated transport chains and regional economies. However, ports are also sites of environmental pollution originating from land-based activities, ship movements and ports’ own activities. It is, therefore, increasingly recognised that economic growth in ports must be balanced with environmental protection and social progress. This has led to enhanced appreciation of the need for sustainable development (SD) in ports. Whilst much has been written about port environmental practices in European and American ports, there is limited synthesis and comparison of sustainable port practices from different parts of the world. Furthermore, in-depth case analysis and critical examination of the practices and challenges of sustainable port development in a globalised era is limited. This paper presents findings from a qualitative multi-case study that aimed to compare sustainable policies and practices of ports in four different continents and to understand the dilemmas, challenges and opportunities they face in attaining SD. This paper reports findings pertaining to the following research questions: (1) What policy frameworks do ports adopt to attain sustainable development? (2) What specific sustainable practices do ports utilise to manage environmental aspects such as air pollution, water quality, ballast water, dredging and disposal of dredged materials, waste disposal, hazardous substances and land/resource use? (3) What are the driving and constraining forces in achieving sustainable development in ports? Port authorities were studied by reviewing documents and secondary data. The following ports were studied: Port of Long Beach (USA), Port of Rotterdam Authority (The Netherlands), Sydney Ports Corporation (Australia) and Transnet Limited that owns and manages South African ports. Findings of the study demonstrate that the SD paradigm has gained momentum, albeit to differing degrees, in the functioning, organisation and the very ethos of case study ports. An important theme from all case studies is that, whilst there is definite progress towards SD, several practices deemed to be sustainable can be controversial and must be critically examined from the perspectives of different stakeholders including shippers, port-related businesses and the local and global community. Lack of data to monitor environmental impacts, economic costs of implementing sustainable practices and complexities of international, regional and national regulations were other constraining factors. On the other hand, reconciling differences between stakeholders and capitalising on economic opportunities, operational efficiencies and cost savings offered by environmental friendliness can advance port SD. Public–private partnerships and policies negotiated by involving all stakeholders were found to foster port sustainability. Most importantly, this study found that, with globalisation, environmental impacts of ports are not always localised. ‘Sustainable’ practices can have unintended consequences in other parts of the world. Therefore, globalisation necessitates a more critical and global analysis of port operations and environment practices in order to be truly sustainable. Although the scope of the research findings is limited to case study ports, the lessons drawn can be constructively applied to any port operating within an institutional system of structured SD.

A genetic and computational approach to structurally classify neuronal types

The importance of cell types in understanding brain function is widely appreciated but only a tiny fraction of neuronal diversity has been catalogued. Here, we exploit recent progress in genetic definition of cell types in an objective structural approach to neuronal classification. The approach is based on highly accurate quantification of dendritic arbor position relative to neurites of other cells. We test the method on a population of 363 mouse retinal ganglion cells. For each cell, we determine the spatial distribution of the dendritic arbors, or “arbor density” with reference to arbors of an abundant, well-defined interneuronal type. The arbor densities are sorted into a number of clusters that is set by comparison with several molecularly defined cell types. The algorithm reproduces the genetic classes that are pure types, and detects six newly clustered cell types that await genetic definition.

Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis

Secondary progressive multiple sclerosis (MS) is typically defined as deterioration independent of relapses for ≥ 6 months following an initial relapsing–remitting course; however, this definition is not always easily applied in clinical practice and the declaration of the change in clinical phenotype is often delayed. To identify the length of time required to re-classify relapsing–remitting MS (RRMS) patients whom have clinically transitioned to secondary progressive MS (SPMS) in clinical practice. We reviewed 123 patients with long-term follow-up and identified a sub-group whom transitioned from RRMS to SPMS, then characterized this transition period. There were 14/20 patients who transitioned during the follow-up period that had visits with uncertainty related to the clinical phenotype characterized by possible, but not definitive progression. The mean duration of this period of uncertainty was 2.9 ± 0.8 years. A period of diagnostic uncertainty regarding the transition from RRMS to SPMS existed in many of our patients. Potential reasons included the subtle nature of early progressive disease and caution in applying a progressive label, in light of the lack of evidence-based treatments as well as third-party payer concerns. Delay in definitive identification of an SPMS phenotype has a variety of implications related to patient care and research.

Necrotizing enterocolitis is one disease with many origins and potential means of prevention

BackgroundThe field of necrotizing enterocolitis (NEC) research has been in existence for over 60 years. During the first five decades little progress in NEC prevention and no definitive progress in treatment was achieved. One of the major determinants of this ineffectiveness may have been a global propensity to lump NEC into a single disease entity rather than a spectrum of diseases with a common outcome. The driver of this philosophy was most likely statistical, in that researchers desired large cohorts to optimize statistical power. Additionally, in the past quarter century, our preterm NEC cohorts were (and in some cases still are) contaminated with spontaneous intestinal perforations (SIP). This completely different acquired neonatal intestinal disease (ANID) markedly alters clinical characteristics and outcomes in NEC cohorts and subsets if not addressed. Unfortunately, cohort size has been proven to be less important than data quality when it comes to NEC over this last decade of research. Emerging progress in NEC prevention has been greatly enhanced as a result of dividing well-defined NEC into subsets of disease origin and investigating these entities individually. Review objectivesThe purpose of this review is to offer the bedside clinician a concise, up-to-date review of recent advances in NEC reductionism. The reader should understand the history and basic theory behind NEC subsets, their application to NEC prevention, and comprehend that prevention of NEC requires a comprehensive quality improvement strategy that is likely best realized with a zero tolerance approach. ConclusionsWe are entering a new era of NEC prevention. NICUs that embrace and achieve effective NEC prevention strategies will rapidly outpace their contemporaries. Because NEC is still the major driver of morbidity and mortality in most NICUs today, those who reject or fail in this pursuit will likely face increasingly severe consequences due to growing requirements for outcomes transparency.

Tryptophan PET-defined gross tumor volume offers better coverage of initial progression than standard MRI-based planning in glioblastoma patients.

Glioblastoma is an infiltrative malignancy that tends to extend beyond the MRI-defined tumor volume. We utilized positron emission tomography (PET) imaging with the radiotracer alpha-[11C]methyl-L -tryptophan (AMT) to develop a reliable high-risk gross tumor volume (HR-GTV) method for delineation of glioblastoma. AMT can detect solid tumor mass and tumoral brain infiltration by increased tumoral tryptophan transport and metabolism via the immunosuppressive kynurenine pathway. We reviewed all patients in our database with histologically proven glioblastoma who underwent preoperative AMT-PET scan prior to surgery and chemoradiation. Treated radiotherapy volumes were derived from the simulation CT with MRI fusion. High-GTV with contrast enhanced T1-weighted MRI alone (GTVMRI) was defined as the postoperative cavity plus any residual area of enhancement on postcontrast T1-weighted images. AMT-PET images were retrospectively fused to the simulation CT, and a high-risk GTVs generated by both AMT-PET alone (GTVAMT) was defined using a threshold previously established to distinguish tumor tissue from peritumoral edema. A composite volume of MRI and AMT tumor volume was also created (combination of MRI fused with AMT-PET data; GTVMRI+AMT). In patients with definitive radiographic progression, follow-up MRI demonstrating initial tumor progression was fused with the pretreatment images and a progression volume was contoured. The coverage of the progression volume by GTVMRI, GTVAMT, and GTVMRI+AMT was determined and compared using the Wilcoxon's signed-rank test. Eleven patients completed presurgical AMT-PET scan, seven of whom had progressive disease after initial therapy. GTVMRI (mean, 50.2 cm3) and GTVAMT (mean, 48.9 cm3) were not significantly different. Mean concordance index of the volumes was 39±15 %. Coverage of the initial recurrence volume by HR-GTVMRI (mean, 52 %) was inferior to both GTVAMT (mean, 68 %; p =0.028) and GTVMRI+AMT (mean 73 %; p =0.018). The AMT-PET-exclusive coverage was up to 41 % of the recurrent volume. There was a tendency towards better recurrence coverage with GTVMRI+AMT than with GTVAMT alone (p =0.068). Addition of 5 mm concentric margin around GTVMRI, GTVAMT, and GTVMRI+AMT would have completely covered the initial progression volume in 14, 57, and 71 % of the patients, respectively. We found that a GTV defined by AMT-PET produced similar volume, but superior recurrence coverage than the treated standard MRI-determined volume. A prospective study is necessary to fully determine the usefulness of AMT-PET for volume definition in glioblastoma radiotherapy planning.

Advances in monoclonal antibody application in myocarditis

Monoclonal antibodies have become a part of daily preparation technologies in many laboratories. Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases, inflammatory diseases, cancer, and other immune-associated diseases. This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis, an inflammatory disease of the heart, could be a novel approach in the future. In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis, we, through a significant amount of literature research both domestic and abroad, developed a systematic elaboration of monoclonal antibodies, pathogenesis of myocarditis, and application of monoclonal antibodies in myocarditis. This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future. Under conventional therapy, myocarditis is typically associated with congestive heart failure as a progressive outcome, indicating the need for alternative therapeutic strategies to improve long-term results. Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis, we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above. However, several issues remain. The technology on how to make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues. If we are to further stimulate progress in the area of clinical decision support, we must continue to develop and refine our understanding and use of monoclonal antibodies in myocarditis.

Clinical diagnostic accuracy of suspected sources of bacteremia and its effect on mortality

BackgroundAlthough much has been written about bacteremia, evidence of the clinical diagnostic accuracy of bacteremia sources in the absence of microbiological results and the impact of diagnostic accuracy on mortality is scarce. MethodsThis is a retrospective study of bacteremia episodes over a 2-year period at a general hospital in Madrid. Congruence analyses between clinically presumed and definite sources, acquisition, causative organism, empirical treatment and progression to death were performed. ResultsThe study included 323 bacteremia episodes. Clinicians' diagnostic accuracy was higher for gastrointestinal (88.8%; 95% CI: 79%–84%), respiratory (93.9%; 95% CI: 79%–99%) and urinary tract sources (83.6%; 95% CI: 75%–89%) and lower for skin and soft tissues (77.2%; 95% CI: 54%–92%) and, notably, intravascular sources (56%; 95% CI: 39%–71%).Overall, a non-significant (3.45%; 95% CI: −0.6%–13.5%, p=0.47) increase in mortality was observed in the incorrectly suspected bacteremia source group.Mortality related to a definitive source was significantly higher when an intravascular origin was not suspected, resulting in a 26% increase in mortality (95% CI: 1%–52%, p=0.03). Differences in mortality related to inaccurate source assumptions were non-significant when the definitive bacteremia sources were gastrointestinal, urinary, respiratory, skin and soft tissues or unknown.Mortality in the group receiving appropriate empirical antimicrobial treatment was 10.6% compared with 19.7% mortality in the group receiving inappropriate empirical antimicrobial treatment (OR 2; 95% CI: 1.01–4.25). ConclusionsThe diagnostic accuracy of bacteremia sources is high in all but intravascular sources. A non-suspected intravascular source and inappropriate empirical treatment are related to a higher mortality.

9.5.2 New Opportunities for Architecture Measurement

AbstractRecent industry progress in architecture definition, architecting tools, model‐based systems engineering, and customer policy has created both a nexus of demand and opportunities to advance the state of architecture measurement. In this paper we describe recent industry working group results and propose architecture measures intended to meet the needs of systems engineers and their program managers as leading indicators of system development health. The measures are documented using the PSM (Practical Software and Systems Measurement) methodology. General techniques are proposed that take advantage of the opportunities afforded by the current architecture modeling environment to provide a basic measurement plan for architecture, including leveraging existing measurement concepts found within the Systems Engineering Leading Indicators. The result is a comprehensive and tailorable suite of measures that can provide decision‐making data to program managers and technical program leaders.

AB1279 Evaluation of different composite radiological indexes for assessment of interstitial lung disease progression in systemic sclerosis

BackgroundHigh-resolution CT (HRCT) is well-established as a sensitive method of detecting and characterizing of interstitial lung disease in systemic sclerosis (ILD-SSc). Several visual scales have been developed for scoring the...

Assessing seasonal changes in carbonate parameters across small spatial gradients in the Northeastern Chukchi Sea

Observations of the marine carbonate system were made in 2010 in the northeastern Chukchi Sea to constrain the seasonal progression of carbonate mineral saturation states (Ω) throughout the water column and determine the air–sea flux of carbon dioxide (CO2). As sea ice retreats from the Chukchi Shelf, primary production consumes dissolved inorganic carbon (DIC) in the euphotic zone causing pH and carbonate mineral saturation states to increase. Throughout the summer and early autumn months of 2010, saturation states for calcite and aragonite ranged from 2.5 to 4.0 and 1.5 to 2.5, respectively, well about the saturation horizon of 1.0. Much of the organic matter produced during the bloom was vertically exported from the relatively small study area leading to an uptake of CO2 from the atmosphere of at least 340,000kg-C. The exported organic matter settled near the bottom and was remineralized back into DIC, causing concentrations to increase sharply, particularly in autumn months, driving down pH to as low as 7.75 and suppressing the concentrations of important carbonate minerals to the point that aragonite became undersaturated. The data showed a definitive seasonal progression of this process with aragonite becoming partially undersaturated along the bottom in September, and broadly undersaturated in October. While carbonate saturation states would naturally be suppressed by the high rates of export production and the accumulation of DIC near the bottom, the penetration of anthropogenic CO2 into the water column (ocean acidification) has caused these observed undersaturations, which will likely expand as CO2 levels in the atmosphere continue to rise in the coming decades.

664 TESTOSTERONE THERAPY IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized (III)1 Apr 2013664 TESTOSTERONE THERAPY IN MEN ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER Mariam Hult and Abraham Morgentaler Mariam HultMariam Hult Brookline, MA More articles by this author and Abraham MorgentalerAbraham Morgentaler Brookline, MA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.219AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Testosterone therapy (TTh) in men with prostate cancer (PCa) is controversial. Only one prior study, involving 13 men, has evaluated TTh in men on active surveillance for PCa. We here report our experience in a larger group of these men. METHODS A chart review was performed for all men in our practice who received TTh during active surveillance for PCa for a minimum of 6 months. Charts were assessed for patient age, pathology, prostate specific antigen (PSA), endocrine results, and cancer progression. Progression was defined by increased number of cores by 3 or more, or persistent increase in Gleason score of 1 or greater. RESULTS A total of 33 men received TTh while on active surveillance. Five received TTh for < 6 months and were excluded from further analysis. The remaining 28 patients had a mean age of 66.8 years (range 54 to 91) and received TTh for a mean of 36.2 + 22.6 months (range 7-81.6). Initial Gleason score was 6 in 26 men, and 7 (3+4) in 2 men. These men underwent an average of 1.1 follow-up biopsies. Testosterone therapy increased mean testosterone from 338 ng/dl at baseline to 594 ng/dl at 6 months (P < 0.0001). No significant increase in mean PSA was noted from baseline to last follow-up (2.8 ng/ml vs 3.0 ng/ml, respectively; P=0.41). No individual demonstrated definite clinical progression. A biopsy revealing an upgrade in Gleason score was noted in 7 men, all of whom had at least one subsequent biopsy revealing the original Gleason score, or no malignancy at all. Two men elected radical prostatectomy despite lack of clinical progression, and 2 discontinued TTh due to lack of efficacy. Of 28 evaluable men, 24 continue with TTh on active surveillance. CONCLUSIONS Testosterone therapy does not appear to cause PCa progression over the short-to-medium term in men with active surveillance. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e271 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mariam Hult Brookline, MA More articles by this author Abraham Morgentaler Brookline, MA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Sphere paths in outer space

We give estimates on the length of paths defined in the sphere model of outer space using a surgery process, and show that they make definite progress in some sense when they remain in some thick part of outer space. To do so, we relate the Lipschitz metric on outer space to a notion of intersection numbers.

Management of Varicose Veins and Venous Insufficiency

Chronic venous disease, reviewed herein, is manifested by a spectrum of signs and symptoms, including cosmetic spider veins, asymptomatic varicosities, large painful varicose veins, edema, hyperpigmentation and lipodermatosclerosis of skin, and ulceration. However, there is no definitive stepwise progression from spider veins to ulcers and, in fact, severe skin complications of varicose veins, even when extensive, are not guaranteed. Treatment options range from conservative (eg, medications, compression stockings, lifestyle changes) to minimally invasive (eg, sclerotherapy or endoluminal ablation), invasive (surgical techniques), and hybrid (combination of ≥1 therapies). Ms L, a 68-year-old woman with varicose veins, is presented. She has had vein problems over the course of her life. Her varicose veins recurred after initial treatment, and she is now seeking guidance regarding her current treatment options.

Formation of dislocation-free nanostructures in metals on electroexplosive alloying

820 Dramatic improvements in functional materials are possible by means of nanostructures [1, 2]. Funda mental research into nanostructures over the past twenty years has resulted in significant modification of the traditional dislocational explanation of strength and plasticity [3]. Definite progress has already been made in terms of pure metals [4]. Considerable research is still required for multiphase composites [5].

Variant on chromosome 9p is associated with left ventricular mass

It is well known that among hypertensive patients, an increased left ventricular mass (LVM) is a powerful predictor of cardiovascular morbidity and mortality. However, the mechanisms underlying LVM in hypertension are not completely understood, as the absolute value of blood pressure and other risk factors associated do not predict alone a definite LVM progression. Recently, the 9p21 chromosomal region has been consistently associated with coronary heart disease. We examined the association of 384 single nucleotide polymorphisms (SNPs) in the short arm of chromosome 9 with LVM in 821 hypertensive individuals from northern Italy. We identified a SNP (rs894379) in the intronic region of the centlein, centrosomal protein (CNTLN) gene on chromosome 9p22, whose minor allele G is associated with an increased LVM. We performed a follow-up validation analysis for the top SNP in 1038 hypertensive individuals from southern Italy. We then combined the results and found a nominal association for rs894379 (β = 2.46, P = 0.0026). We describe a new variant associated with echocardiography LVM. This result, though it needs to be further investigated, may improve our understanding of the genetic determination of this prognostically relevant trait.

Screening for pre‐diabetes to predict future diabetes using various cut‐off points for HbA1c and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4)

To evaluate various screening criteria for pre-diabetes to identify which combination of impaired fasting glucose and elevated HbA(1c) values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals. The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose ≥ 7.0 mmol/l, HbA(1c) ≥ 48 mmol/mol (≥ 6.5%), or self-reported clinician-diagnosed diabetes). Pre-diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l or 6.1-6.9 mmol/l) and elevated HbA(1c) [39-46 mmol/mol (5.7-6.4%) or 42-46 mmol/mol (6.0-6.4%)]. During a 5-year follow-up, 338 incident cases of diabetes occurred. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l yielded the highest sensitivity (86%) and generated a large population-attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre-diabetes by any of the four combined criteria, 20.5-32.0% reverted to the normoglycaemic state as having neither elevated HbA(1c) nor impaired fasting glucose at the last follow-up examination. At 5.6 years after the baseline examination, however, pre-diabetic individuals who fulfilled both HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l had a 100% cumulative risk of developing diabetes. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre-diabetic individuals who strictly fulfil HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l would predict definite progression to diabetes.