Cognitive-behaviour therapy and skilled motor performance in adults with chronic tic disorder

The first aim of the present study was to compare performance of people with tic disorders (TD) and controls on executive function and a range of skilled motor tests requiring complex performance, guided movements, hand co-ordination, and fine control of steadiness. The second aim was to investigate the effect of cognitive behaviour therapy (CBT) on motor performance. A total of 55 patients with TD were recruited at baseline from participants in a behavioural management programme. A comparison group of 55 patients suffering from a variety of habit disorders (HD) involving complex manual movements, were matched on age and level of education to 34 non-psychiatric controls. Participants were evaluated pre- and post-treatment and post-waitlist with a neuropsychological evaluation focusing on executive function (Wisconsin Card Sorting Test, WCST) and skilled motor performance (Purdue Pegboard, Hole Steadiness Test, and the Groove Test). Results revealed WCST scores in the normal range, while motor performance differed significantly on the Purdue Pegboard Tests in both TD and HD as compared to the control group. Cognitive-behavioural treatment selectively improved motor performance in both clinical groups compared to waitlist control, and this improvement related to clinical outcome measures

Subclinical infection of macaques and baboons with a baboon simarterivirus

Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2–advanced breast cancer: GEICAM/2014–12 (FLIPPER)

Background The potential benefit of adding palbociclib to fulvestrant as first-line treatment in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative endocrine-sensitive advanced breast cancer (ABC) patients remains uncharacterized. Patients and methods In this randomized (1:1), double-blind, phase II study, postmenopausal women with HR-positive, HER2-negative ABC with de novo metastatic disease or those who relapsed after >12 months of adjuvant endocrine therapy received palbociclib/fulvestrant or placebo/fulvestrant. Stratification was based on recurrent versus de novo metastatic disease and visceral involvement. The primary objective was one-year progression-free survival (PFS-1y) rate. The sample size was 190 patients. The two-sided alpha of 0.2, 80% of power to detect a difference between the arms, assuming PFS rates of 0.695 and 0.545 for palbociclib/fulvestrant and placebo/fulvestrant, respectively. Results In total, 189 patients were randomized to palbociclib/fulvestrant ([n = 94] or placebo/fulvestrant [n = 95]). 45.5% and 60.3% of patients had de novo metastatic disease and visceral involvement, respectively. PFS-1y rates were 83.5% and 71.9% in the palbociclib/fulvestrant and placebo/fulvestrant arms, (HR 0.55, 80% CI 0.36–0.83, P = 0.064). The median PFS were 31.8 and 22.0 months for the palbociclib/fulvestrant and placebo/fulvestrant arms (aHR 0.48, 80% CI 0.37–0.64, P = 0.001). The most frequent grade 3–4 adverse events were neutropenia (68.1% vs. 0%), leucopenia (26.6% vs. 0%), anemia (3.2% vs. 0%), and lymphopenia (14.9% vs. 2.1%) for the palbociclib/fulvestrant and placebo/fulvestrant, respectively. The most frequent non-hematologic grade 3–4 adverse event was fatigue (4.3% vs. 0%). Conclusions Palbociclib/fulvestrant demonstrated better PFS-1y rates and median PFS than placebo/fulvestrant in HR-positive/HER2-negative endocrine-sensitive ABC patients

Statistical Mechanics for Unstable States in Gel'fand Triplets and Investigations of Parabolic Potential Barriers

Free energies and other thermodynamical quantities are investigated in canonical and grand canonical ensembles of statistical mechanics involving unstable states which are described by the generalized eigenstates with complex energy eigenvalues in the conjugate space of Gel'fand triplet. The theory is applied to the systems containing parabolic potential barriers (PPB's). The entropy and energy productions from PPB systems are studied. An equilibrium for a chemical process described by reactions $A+CB\rightleftarrows AC+B$ is also discussed.Comment: 14 pages, AmS-LaTeX, no figur

Molecular Genetic Approaches to Disease of Neural Development

This study utilized novel genetic techniques in order to find causative gene mutations that underlie diseases of neural development. Our laboratory has collected 175 cases of malformations of cortical development (MCD) from the United States and Europe. Four of these cases are the focus of this manuscript: two familial cases of infantile neuroaxonal dystrophy (INAD), a familial case of hereditary spastic paraparesis (HSP), and a sporadic case of Greig cephalopolysyndactyly (GCPS) and cerebral cavernous malformations (CCMs). The techniques utilized to study the affected patients include microarray-based single nucleotide polymorphism (SNP) genotyping and copy number variation (CNV) analysis, both of which are powerful tools in the hunt for disease-causing gene mutations. In the familial cases of INAD, we report two novel mutations in the PLA2G6 gene, previously shown to cause INAD when mutated. In the familial case of HSP, we demonstrate linkage to the SPG11 locus on chromosome 15q. Finally, in the sporadic case of GCPS and CCM, we published the first report on this novel syndrome along with a genetic analysis that demonstrates a microdeletion on chromosome 7p, resulting in heterozygous loss of both the GLI3 and CCM2 genes. The three studies presented in this manuscript demonstrate the utility of SNP genotyping and CNV analysis in revealing the genetic mutations that underlie diseases of neural development

The impact of policy modifiable factors on inequalities in rates of child dental caries in Australia

Background: Poor oral health in childhood can lead to adverse impacts later in life. We aimed to estimate the prevalence and population distribution of childhood dental caries in Australia and investigate factors that might ameliorate inequalities. Methods: Data from the nationally representative birth cohort Longitudinal Study of Australian Children (N = 5107), using questions assessing: The experience of dental caries during each biennial follow-up period (2-3 years to 10-11 years), socioeconomic position (SEP), and policy modifiable oral health factors. Results: The odds of dental caries were higher for children with lowest vs. highest SEP (adjusted OR (adjOR) 1.92, 95% CI 1.49-2.46), and lower where water was fluoridated to recommended levels (adjOR 0.53, 95% CI 0.43-0.64). There was no evidence of an association between caries experience and either reported sugary diet or tooth brushing. When SEP and fluoridation were considered in conjunction, compared to the highest SEP group with water fluoridation children in the lowest SEP with fluoridation had adjOR 1.54 for caries, (95% CI 1.14-2.07), and children in the lowest SEP without fluoridation had adjOR 4.06 (95% CI 2.88-5.42). For patterns of service use: The highest SEP group reported a greater percentage of service use in the absence of caries. Conclusions: Dental caries appears prevalent and is socially distributed in Australia. Policy efforts should consider how to ensure that children with dental caries receive adequate prevention and early care with equitable uptake.Sharon Goldfeld, Kate Louise Francis, Monsurul Hoq, Loc Do, Elodie O’Connor, and Fiona Mensa

Chandra and Magellan /FIRE follow-up observations of PSO167-13: An X-ray weak QSO at z = 6.515

Context. The discovery of hundreds of quasi-stellar objects (QSOs) in the first gigayear of the Universe powered by already grown supermassive black holes (SMBHs) challenges our knowledge of SMBH formation. In particular, investigations of z  >  6 QSOs that present notable properties can provide unique information on the physics of fast SMBH growth in the early Universe. Aims. We present the results of follow-up observations of the z  =  6.515 radio-quiet QSO PSO167-13, which is interacting with a close companion galaxy. The PSO167-13 system has recently been proposed to host the first heavily obscured X-ray source at high redshift. The goals of these new observations are to confirm the existence of the X-ray source and to investigate the rest-frame UV properties of the QSO. Methods. We observed the PSO167-13 system with Chandra/ACIS-S (177 ks) and obtained new spectroscopic observations (7.2 h) with Magellan/FIRE. Results. No significant X-ray emission is detected from the PSO167-13 system, suggesting that the obscured X-ray source previously tentatively detected was either due to a strong background fluctuation or is highly variable. The upper limit (90% confidence level) on the X-ray emission of PSO167-13 (L2-10  keV  <  8.3 × 1043  erg  s-1) is the lowest available for a z  >  6 QSO. The ratio between the X-ray and UV luminosity of αox  <  -1.95 makes PSO167-13 a strong outlier from the αox - LUV and LX - Lbol relations. In particular, its X-ray emission is more than six times weaker than the expectation based on its UV luminosity. The new Magellan/FIRE spectrum of PSO167-13 is strongly affected by unfavorable sky conditions, but the tentatively detected C IV and Mg II emission lines appear strongly blueshifted. Conclusions. The most plausible explanations for the X-ray weakness of PSO167-13 are intrinsic weakness or small-scale absorption by Compton-thick material. The possible strong blueshift of its emission lines hints at the presence of nuclear winds, which could be related to its X-ray weakness