A visual conflict hypothesis for global-local visual deficits in Williams Syndrome: simulations and data

Individuals with Williams Syndrome demonstrate impairments in visuospatial cognition. This has been ascribed to a local processing bias. More specifically, it has been proposed that the deficit arises from a problem in disengaging attention from local features. We present preliminary data from an integrated empirical and computational exploration of this phenomenon. Using a connectionist model, we first clarify and formalize the proposal that visuospatial deficits arise from an inability to locally disengage. We then introduce two empirical studies using Navon-style stimuli. The first explored sensitivity to local vs. global features in a perception task, evaluating the effect of a manipulation that raised the salience of global organization. Thirteen children with WS exhibited the same sensitivity to this manipulation as CA-matched controls, suggesting no local bias in perception. The second study focused on image reproduction and demonstrated that in contrast to controls, the children with WS were distracted in their drawings by having the target in front of them rather than drawing from memory. We discuss the results in terms of an inability to disengage during the planning stage of reproduction due to over-focusing on local elements of the current visual stimulus

Cross-cultural differences in temperament: Comparing paternal ratings of US and Dutch infants

This study conducted longitudinal comparisons of US and Dutch paternal ratings of temperament, measured via the Infant Behaviour Questionnaire-Revised, at 4 months (US n = 99; Dutch n = 127) and 12 months (US n = 66; Dutch n = 112) of age. US fathers rated their infant higher in the broad temperament trait Surgency, and its subscales vocal reactivity, high-intensity pleasure, and activity level. US fathers also rated their infants higher in negative emotionality, and its subscales of sadness, distress to limitations, and fear. Dutch infants received higher ratings in falling reactivity. Though the cultures did not differ in ratings of Orienting/regulatory capacity, US infants were higher on the subscale duration of orienting, and lower in soothability. Significant culture-by-age and culture-by-gender interactions were also noted. Overall, results are largely consistent with those reported for Dutch mothers and speak to considerable differences in early temperament development between cultures viewed as largely similar because of their Western/individualistic orientations

Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in doberman pinschers with preclinical dilated cardiomyopathy (the PROTECT study)

<p>Background: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported.</p> <p>Hypothesis: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival.</p> <p>Animals: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America.</p> <p>Methods: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo.</p> <p>The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint.</p> <p>Results: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441–1152 days) versus the placebo group (441 days, IQR 151–641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491–1531 days) versus the placebo group (466 days, IQR 236–710 days) (log-rank P = .034).</p> <p>Conclusion and Clinical Importance: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.</p&gt

Collectivity Embedded in Complex Spectra of Finite Interacting Fermi Systems: Nuclear Example

The mechanism of collectivity coexisting with chaos in a finite system of strongly interacting fermions is investigated. The complex spectra are represented in the basis of two-particle two-hole states describing the nuclear double-charge exchange modes in $^{48}$Ca. An example of $J^{\pi}=0^-$ excitations shows that the residual interaction, which generically implies chaotic behavior, under certain specific and well identified conditions may create strong transitions, even much stronger than those corresponding to a pure mean-field picture. Such an effect results from correlations among the off-diagonal matrix elements, is connected with locally reduced density of states and a local minimum in the information entropy.Comment: 16 pages, LaTeX2e, REVTeX, 8 PostScript figures, to appear in Physical Review

A mixed-methods feasibility study of a comorbidity-adapted exercise program for low back pain in older adults (COMEBACK):a protocol

BACKGROUND: The prevalence of low back pain increases with age and has a profound impact on physical and psychosocial health. With increasing age comes increasing comorbidity, and this also has pronounced health consequences. Whilst exercise is beneficial for a range of health conditions, trials of exercise for low back pain management often exclude older adults. It is currently unknown whether an exercise program for older adults with low back pain, tailored for the presence of comorbidities, is acceptable for participants and primary healthcare providers (PHCPs). Therefore, this mixed-methods study will assess the feasibility of an 8-week comorbidity-adapted exercise program for older people with low back pain and comorbid conditions. METHODS: The 3-phased feasibility study will be performed in a primary healthcare setting. PHCPs will be trained to deliver a comorbidity-adapted exercise program for older people with low back pain and comorbidities. Healthcare-seeking adults > 65 will be screened for eligibility over telephone, with a recruitment target of 24 participants. Eligible participants will attend an initial appointment (diagnostic phase). During this initial appointment, a research assistant will collect patient demographics, self-reported outcome measurement data, and perform a physical and functional examination to determine contraindications and restrictions to an exercise program. During the development phase, PHCPs will adapt the exercise program to the individual and provide patient education. During the intervention phase, there will be two supervised exercise sessions per week, over 8 weeks (total of 16 exercise sessions). Each exercise session will be approximately 60 min in duration. A qualitative evaluation after the last exercise program session will explore the feasibility of the exercise program for participants and PHCPs. Progression criteria will determine the suitability for a fully powered randomised controlled trial. DISCUSSION: This mixed-methods feasibility study will assess an exercise program for older adults with low back pain and comorbidities. Once assessed for feasibility, the exercise program may be tested for effectiveness in a larger, fully powered randomised controlled trial. This information will add to the sparse evidence base on appropriate options for managing back pain in older adults. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry registration number: ACTRN12621000379819p (06/04/2021; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000379819p). TRIAL SPONSOR: Macquarie University, Department of Chiropractic, Faculty of Medicine, Health and Human Sciences, Macquarie University, NSW 2109, Australia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40814-022-01097-x

Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS

Spectral fluctuation properties of spherical nuclei

The spectral fluctuation properties of spherical nuclei are considered by use of NNSD statistic. With employing a generalized Brody distribution included Poisson, GOE and GUE limits and also MLE technique, the chaoticity parameters are estimated for sequences prepared by all the available empirical data. The ML-based estimated values and also KLD measures propose a non regular dynamic. Also, spherical odd-mass nuclei in the mass region, exhibit a slight deviation to the GUE spectral statistics rather than the GOE.Comment: 10 pages, 2 figure

Mortality and cancer incidence among underground uranium miners in the Czech Republic 1977-1992

Objectives Uranium miners in Příbram, Czech Republic were exposed to low and moderate levels of radon gas and other hazards. It is unknown whether these hazards increase the risk of mortality or cancer incidence when compared with the general Czech population. Methods A cohort of 16 434 male underground miners employed underground for at least 1 year between 1946 and 1976, and alive and residing in the Czech Republic in 1977, were followed for mortality and cancer incidence through 1992. We compared observed deaths and cancer incidence to expectation based on Czech rates. Standardised mortality ratios (SMRs), standardised incidence ratios (SIRs) and causal mortality ratios were calculated. Results Underground workers in the Příbram mines had higher rates of death than expected due to all causes (SMR=1.23, 95% CI 1.20 to 1.27), all cancers (SMR=1.52, 95% CI 1.44 to 1.60), lung cancer (SMR=2.12, 95% CI 1.96 to 2.28) and extrathoracic cancer (SMR=1.41, 95% CI 1.15 to 1.77). Similar excess was observed in cancer incidence analyses, with the addition of stomach cancer (SIR=1.37, 95% CI 1.11 to 1.63), liver cancer (SIR=1.70, 95% CI 1.16 to 2.25) and rectal cancer (SIR=1.41, 95% CI 1.16 to 1.66). The SIR was elevated for all leukaemias (SIR=1.51, 95% CI 1.08 to 2.07) and for lymphatic and haematopoietic cancers combined (SIR=1.31, 95% CI 1.05 to 1.61), but results for specific subtypes were imprecise. Deaths due to hazardous mining conditions resulted in 0.33 person-years of life lost per miner. Conclusions Occupational exposure to the Příbram mines resulted in excess cancers at several sites, including sites previously linked to radon and uranium exposure. Incidence analyses showed relative excess of several additional cancer subtypes

Impaired liver regeneration in mice lacking methionine adenosyltransferase 1A

Methionine adenosyltransferase (MAT) is an essential enzyme because it catalyzes the formation of S-adenosylmethionine (SAMe), the principal biological methyl donor. Of the two genes that encode MAT, MAT1A is mainly expressed in adult liver and MAT2A is expressed in all extrahepatic tissues. Mice lacking MAT1A have reduced hepatic SAMe content and spontaneously develop hepatocellular carcinoma. The current study examined the influence of chronic hepatic SAMe deficiency on liver regeneration. Despite having higher baseline hepatic staining for proliferating cell nuclear antigen, MAT1A knockout mice had impaired liver regeneration after partial hepatectomy (PH) as determined by bromodeoxyuridine incorporation. This can be explained by an inability to up-regulate cyclin D1 after PH in the knockout mice. Upstream signaling pathways involved in cyclin D1 activation include nuclear factor kappaB (NFkappaB), the c-Jun-N-terminal kinase (JNK), extracellular signal-regulated kinases (ERKs), and signal transducer and activator of transcription-3 (STAT-3). At baseline, JNK and ERK are more activated in the knockouts whereas NFkappaB and STAT-3 are similar to wild-type mice. Following PH, early activation of these pathways occurred, but although they remained increased in wild-type mice, c-jun and ERK phosphorylation fell progressively in the knockouts. Hepatic SAMe levels fell progressively following PH in wild-type mice but remained unchanged in the knockouts. In culture, MAT1A knockout hepatocytes have higher baseline DNA synthesis but failed to respond to the mitogenic effect of hepatocyte growth factor. Taken together, our findings define a critical role for SAMe in ERK signaling and cyclin D1 regulation during regeneration and suggest chronic hepatic SAMe depletion results in loss of responsiveness to mitogenic signals