Progression in behavioral variant frontotemporal dementia:A longitudinal study

Importance: A gap in the literature exists regarding progression in behavioral variant frontotemporal dementia (BVFTD). Guidance is needed concerning markers that will enable clinicians to discriminate FTD more effectively from phenocopies and to identify factors that determine progression and thereby prognosis.  Objectives: To observe longitudinal outcomes and progression in probable and possible BVFTD in accordance with international diagnostic criteria and to identify features that may aid clinicians to prognosticate better in cases of possible BVFTD.  Design, Setting, and Participants: Longitudinal cohort study performed in a specialist tertiary FTD research clinic. Fifty-eight consecutive patients were followed up longitudinally from January 1, 2008, through December 31, 2013, and classified as having possible, probable, or definite BVFTD at presentation and latest review. Final follow-up was completed on December 31, 2013, and data were analyzed from January 1 to August 1, 2014.  Main Outcomes and Measures: Clinical, pathological, genetic, neuropsychological, and neuroimaging data were analyzed to categorize patients, to compare differences between groups with changed and unchanged diagnoses, to determine rates of progression in BVFTD, and to identify prognostic features in possible BVFTD.  Results: At presentation, 38 of the 58 patients fulfilled criteria for probable BVFTD; of these, 36 continued to satisfy probable criteria or underwent conversion to definite criteria over time. The remaining 20 patients satisfied possible criteria only, and 11 of these patients changed categories over time to probable or definite BVFTD and showed progression on cognitive and functional measures (termed changed status). Of these 11 patients, 8 (73%) carried the C9orf72 expansion. A positive family history, memory impairment, and clinical abnormalities at presentation were key features of progression (P < .05). A continuum of neuropsychological scores, progression rates, and atrophy severity emerged across patients in probable, possible, changed status, and nonchanged status groups; patients with probable BVFTD exhibited the most severe abnormalities.  Conclusions and Relevance: Behavioral variant FTD shows variable progression over time. Clinicians can use a detailed neurologic and cognitive assessment to identify key predictive features of progression when faced with possible BVFTD, whereas a diagnosis of probable BVFTD is accurate in a clinical setting

Ground-state fidelity of Luttinger liquids: A wave functional approach

We use a wave functional approach to calculate the fidelity of ground states in the Luttinger liquid universality class of one-dimensional gapless quantum many-body systems. The ground-state wave functionals are discussed using both the Schrodinger (functional differential equation) formulation and a path integral formulation. The fidelity between Luttinger liquids with Luttinger parameters K and K' is found to decay exponentially with system size, and to obey the symmetry F(K,K')=F(1/K,1/K') as a consequence of a duality in the bosonization description of Luttinger liquids.Comment: 13 pages, IOP single-column format. Sec. 3 expanded with discussion of short-distance cut-off. Some typos corrected. Ref. 44 in v2 is now footnote 2 (moved by copy editor). Published versio

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a “driver” phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine–substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.Fil: Lui, Vivian Wai Yan. University of Pittsburgh; Estados UnidosFil: Peyser, Noah D.. University of Pittsburgh; Estados UnidosFil: Ng, Patrick Kwok-Shing. University Of Texas Md Anderson Cancer Center;Fil: Hritz, Jozef. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados Unidos. Masaryk University; República ChecaFil: Zeng, Yan. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Lu, Yiling. University Of Texas Md Anderson Cancer Center;Fil: Li, Hua. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Wang, Lin. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Gilbert, Breean R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: General, Ignacio. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Bahar, Ivet. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Ju, Zhenlin. University Of Texas Md Anderson Cancer Center;Fil: Wang, Zhenghe. Case Western Reserve University; Estados UnidosFil: Pendleton, Kelsey P.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Xiao, Xiao. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Du, Yu. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Vries, John K.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Hammerman, Peter S.. Harvard Medical School; Estados UnidosFil: Garraway, Levi A.. Harvard Medical School; Estados UnidosFil: Mills, Gordon B.. University Of Texas Md Anderson Cancer Center;Fil: Johnson, Daniel E.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Grandis, Jennifer R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unido

Short- and Long-Term Propagation of Spacecraft Orbits

The Planetary Observer Planning Software (POPS) comprises four computer programs for use in designing orbits of spacecraft about planets. These programs are the Planetary Observer High Precision Orbit Propagator (POHOP), the Planetary Observer Long-Term Orbit Predictor (POLOP), the Planetary Observer Post Processor (POPP), and the Planetary Observer Plotting (POPLOT) program. POHOP and POLOP integrate the equations of motion to propagate an initial set of classical orbit elements to a future epoch. POHOP models shortterm (one revolution) orbital motion; POLOP averages out the short-term behavior but requires far less processing time than do older programs that perform long-term orbit propagations. POPP postprocesses the spacecraft ephemeris created by POHOP or POLOP (or optionally can use a less accurate internal ephemeris) to search for trajectory-related geometric events including, for example, rising or setting of a spacecraft as observed from a ground site. For each such event, POPP puts out such user-specified data as the time, elevation, and azimuth. POPLOT is a graphics program that plots data generated by POPP. POPLOT can plot orbit ground tracks on a world map and can produce a variety of summaries and generic ordinate-vs.-abscissa plots of any POPP data

Radio Astronomy

Contains reports on isx research projects.National Aeronautics and Space Administration, Langley Research Center (Contract NAS1-10693)National Science Foundation (Grant GP-21348)National Science Foundation (Grant GP-14589)California Institute of Technology Contract 952568Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-030

Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case Studies

The C9orf72 genetic mutation is the most common cause of familial frontotemporal dementia (FTD) and motor neuron disease (MND). Previous family studies suggest that while some common clinical features may distinguish gene carriers from sporadic patients, the clinical features, age of onset and disease progression vary considerably in affected patients. Whilst disease presentations may vary across families, age at disease onset appears to be relatively uniform within each family. Here, we report two individuals with a C9orf72 repeat expansion from two generations of the same family with markedly different age at disease onset, clinical presentation and disease progression: one who developed motor neuron and behavioural symptoms in their mid 40s and died 3 years later with confirmed TDP-43 pathology and MND; and a second who developed cognitive and mild behavioural symptoms in their mid 70s and 8 years later remains alive with only slow deterioration. This report highlights the phenotypic variability, including age of onset, within a family with the C9orf72 repeat expansion

A 6-point TACS score predicts in-hospital mortality following total anterior circulation stroke

Background and Purpose: Little is known about the factors associated with in-hospital mortality following total anterior circulation stroke (TACS). We examined the characteristics and comorbidity data for TACS patients in relation to in-hospital mortality with the aim of developing a simple clinical rule for predicting the acute mortality outcome in TACS. Methods: A routine data registry of one regional hospital in the UK was analyzed. The subjects were 2,971 stroke patients with TACS (82% ischemic; median age=81 years, interquartile age range=74–86 years) admitted between 1996 and 2012. Uni- and multivariate regression models were used to estimate in-hospital mortality odds ratios for the study covariates. A 6-point TACS scoring system was developed from regression analyses to predict in-hospital mortality as the outcome. Results: Factors associated with in-hospital mortality of TACS were male sex [adjusted odds ratio (AOR)=1.19], age (AOR=4.96 for ≥85 years vs. <65 years), hemorrhagic subtype (AOR=1.70), nonlateralization (AOR=1.75), prestroke disability (AOR=1.73 for moderate disability vs. no symptoms), and congestive heart failure (CHF) (AOR=1.61). Risk stratification using the 6-point TACS Score [T=type (hemorrhage=1 point) and territory (nonlateralization=1 point), A=age (65–84 years=1 point, ≥85 years=2 points), C=CHF (if present=1 point), S=status before stroke (prestroke modified Rankin Scale score of 4 or 5=1 point)] reliably predicted a mortality outcome: score=0, 29.4% mortality; score=1, 46.2% mortality [negative predictive value (NPV)=70.6%, positive predictive value (PPV)=46.2%]; score=2, 64.1% mortality (NPV=70.6, PPV=64.1%); score=3, 73.7% mortality (NPV=70.6%, PPV=73.7%); and score=4 or 5, 81.2% mortality (NPV=70.6%, PPV=81.2%). Conclusions: We have identified the key determinants of in-hospital mortality following TACS and derived a 6-point TACS Score that can be used to predict the prognosis of particular patients

Bony metastases from breast cancer - a study of foetal antigen 2 as a blood tumour marker

Background : Foetal antigen 2 (FA-2), first isolated in the amniotic fluid, was shown to be the circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I. Serum concentrations of FA-2 appeared to be elevated in a number of disorders of bone metabolism. This paper is the first report of its role as a marker of bone metabolism in metastatic breast cancer. Methods: Serum FA-2 concentrations were measured by radioimmunoassay in 153 women with different stages of breast cancer and in 34 normal controls. Results: Serum FA-2 was significantly elevated in women with bony metastases (p < 0.015). Its levels were not significantly different among women with non-bony metastases, with non-metastatic disease, as well as among normal controls. Conclusions: FA-2 is a promising blood marker of bone metabolism. Further studies to delineate its role in the diagnosis and management of bony metastases from breast cancer are required