Miracle-dz/UniFAR-FTUs huggingface dataset:
The pathophysiology of schizophrenia disorders: perspectives from the spectrum.

OBJECTIVE This overview focuses on neurobiological abnormalities found in subjects with schizotypal personality disorder, the prototype of the schizophrenia spectrum disorders, and chronic schizophrenia in the context of common vulnerabilities shared by schizotypal personality disorder and schizophrenia, as well as the factors that protect against the severe cognitive/social deficits and frank psychosis of chronic schizophrenia. A pathophysiological model of the relationship between schizotypal personality disorder and schizophrenia was developed based on this data. METHOD The authors provide a selective review of major findings regarding the pathophysiology of schizotypal personality disorder and integrate these results in conjunction with preclinical studies into a model of the pathophysiology of the spectrum. RESULTS People with schizotypal personality disorder share phenomenological, genetic, and cognitive abnormalities with people with chronic schizophrenia. While temporal volume reductions appear to be common to both groups, there may be preservation of frontal lobe volume in schizotypal personality disorder compared to schizophrenia. Findings to date regarding striatal volume, metabolic rate, and dopamine release in subjects with schizotypal personality disorder compared to subjects with chronic schizophrenia are consistent with hypotheses of reduced striatal dopaminergic activity in schizotypal personality disorder compared to schizophrenia. CONCLUSIONS Genetic or environmental factors that promote greater frontal capacity and reduced striatal dopaminergic reactivity might contribute to sparing people with schizotypal personality disorder from the psychosis and severe social and cognitive deterioration of chronic schizophrenia. Further research is required to test these hypotheses more definitively.
Hippocampal Synaptic Metaplasticity Requires Inhibitory Autophosphorylation of Ca 2ϩ /calmodulin-dependent Kinase Ii

Virtually all CNS synapses display the potential for activity-dependent long-term potentiation (LTP) and/or long-term depression (LTD). Intriguingly, the potential to exhibit LTP or LTD at many central synapses itself is powerfully modulated by previous synaptic activity. This higher-order form of plasticity has been termed metaplasticity. Here, we show that inhibitory autophosphorylation of Ca 2ϩ / calmodulin-dependent kinase II (CaMKII) is required for hippocampal metaplasticity at the lateral perforant path– dentate granule cell synapse. Brief 10 Hz priming, which does not affect basal synaptic transmission, caused a dramatic, pathway-specific and long-lasting (up to 18 h) reduction in subsequently evoked LTP at lateral perforant path synapses. In contrast, LTD was unaffected by priming. The induction of lateral perforant path metaplasticity required the activation of NMDA receptors during priming. In addition, metaplasticity was absent in knock-in mice expressing ␣CaMKII that cannot undergo inhibitory phosphorylation, indicating that inhibitory autophos-phorylation of ␣CaMKII at threonines 305/306 is required for metaplasticity. Metaplasticity was not observed in the medial perforant pathway, consistent with the observation that CaMKII activity was not required for the induction of LTP at this synapse. Thus, modulation of ␣CaMKII activity via autophosphorylation at Thr305/Thr306 is a key mechanism for metaplasticity that may be of importance in the integration of temporally separated episodes of activity.
Review Article Peroxisome Proliferator-activated Receptors (ppars) as Potential Inducers of Antineoplastic Effects in Cns Tumors

The peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS). The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.
Performance of multilayer optical coatings under long-term 532nm laser exposure

The effects of long-term exposure to high intensity 532 nm radiation on various dielectric-coated optics are studied. To investigate potential photodarkening effects on optical surfaces, an accelerated life test platform was constructed where optics were exposed to 532 nm radiation from a short-pulse, high repetition rate fiber amplifier at total doses up to 1 trillion shots. The first run of trillion-shot tests were conducted on e-beam deposited and ion beam sputtering (IBS) coated high reflecting mirrors with onsurface intensities ranging from 1.0-1.4 GW/cm2. It was found that the e-beam coated mirrors failed catastrophically at less than 150 billion shots, while the IBS coated mirror was able to complete the trillionshot test with no measurable loss of reflectivity. Profiling the IBS mirror surface with a high-resolution white light interferometer post-irradiation revealed a ~10 nm high photocontamination deposit at the irradiation site that closely matched the intensity profile of the laser spot. Trillion-shot surface exposure tests were also conducted at multiple surface sites of an LBO frequency doubling crystal at ~1.5 GW/cm2 at multiple surface sites. The transmitted power and on-surface beam size were monitored throughout the tests, and periodic measurements of the beam quality and waist location of the transmitted light were also made using an M2 meter. No changes in transmitted power or M2 were observed in any of the tests, but 3D surface profiling revealed laser-induced contamination deposits at each site tested.
Prioritizing new objects for eye fixation in real-world scenes: Effects of object–scene consistency

Recent research suggests that new objects appearing in real-world scenes are prioritized for eye fixations and by inference, for attentional processing. We examined whether semantic consistency modulates the degree to which new objects appearing in a scene are prioritized for viewing. New objects were added to photographs of real-world scenes during a fixation (new object with transient onset) or during a saccade (new object without transient onset). The added object was either consistent or inconsistent with the scene's meaning. Object consistency did not affect the efficacy with which transient onsets captured attention, suggesting that transient motion signals capture attention in a bottom-up manner. Without a transient motion signal, the semantic consistency of the new object affected its prioritization with new inconsistent objects fixated sooner than new consistent objects, suggesting that attention prioritization without capture is a top-down memory-based phenomenon at least partially controlled by object identity and meaning.
Hand grip strength: A phenotype suitable for identifying genetic variants affecting mid‐ and late‐life physical functioning

Physical functioning late in life has been shown to be affected by genetic factors. Only a few genetic variants have been suggested to be associated with physical functioning, and this only in selected populations (e.g., young healthy males and elite athletes). Declining physical functioning late in life is a major problem in terms of prevalence, morbidity, functional limitations, and quality of life. It is therefore of interest to find a phenotype reflecting physical functioning which has a relatively high heritability and which can be measured in large samples. Hand grip strength is known to be associated with muscular functioning in other muscle groups and with activities of daily living (ADL) functioning, and it predicts incident disability. We studied 1,757 Danish twin pairs aged 45–96 years, and found that this phenotype has a heritability of 52% (95% confidence interval (CI), 48–55%). A powerful design to detect genes associated with a phenotype is obtained using the extreme discordant and concordant sib pairs, of whom 28 and 77 dizygotic twin pairs, respectively, were found in this study. Hence grip strength is a suitable phenotype for identifying genetic variants of importance to mid‐ and late‐life physical functioning. Genet. Epidemiol. 23:110–122, 2002. © 2002 Wiley‐Liss, Inc.
A comparison of three multiple-attenuation methods for a Gulf of Mexico dataset

Three multiple attenuation techniques are tested on a Gulf of Mexico dataset. These methods are (1) a hyperbolic Radon transform followed by a mute (2), the Delft approach and (3), a pattern-based technique. The Radon transform separates multiples and primaries according to their moveout. The Delft approach models the multiples and subtracts them by estimating adaptive filters. The pattern-based method us es the multiple model from the Delft approach to extract and separate multiples from the primaries according to their multivariate spectra. Because of the complex geology and the modeling uncertainties introduced by 3-D effects and the acquisition geometry, the Radon transform and the Delft approach do not perform as well as the pattern-based method. In addition, the pattern-based method works significantly better when higher dimension filt ers are utilized: diffracted multiples are well attenuated while preserving the primaries.
Stepwise Kaizen Parameters Improvement via the Path of Steepest Ascent

Kaizen has been widely accepted as a continuous process improvement with the gradualist approach. This paper presents research carried out to explore a pattern of an investment in Kaizen to enhance overall profit. System dynamics-based simulation has been employed with an optimization technique, a Steepest Ascent approach, to improve experimental variables e.g. the amount of spending on prevention and appraisal activities, the time and the amount to reduce the investment which results in maximum Net Present Value (NPV) of profit. The simulation model in this study is based on a Thai automobile manufacturer as a case study company. The result suggests that the investment in Kaizen should be reduced economically when the process is under controlled. It can be named as the ‘Stepwise Kaizen’, which was proved in this study that it provides greater overall profit than the constant spending. This study also presents the behavior of quality costs and profit against time scale along the Stepwise Kaizen implementation.
Ultra-Deep Pyrosequencing of Partial Surface Protein Genes from Infectious Salmon Anaemia Virus (ISAV) Suggest Novel Mechanisms Involved in Transition to Virulence

Uncultivable HPR0 strains of infectious salmon anaemia viruses (ISAVs) infecting gills are non-virulent putative precursors of virulent ISAVs (vISAVs) causing systemic disease in farmed Atlantic salmon (Salmo salar). The transition to virulence involves two molecular events, a deletion in the highly polymorphic region (HPR) of the hemagglutinin-esterase (HE) gene and a Q266→L266 substitution or insertion next to the putative cleavage site (R267) in the fusion protein (F). We have performed ultra-deep pyrosequencing (UDPS) of these gene regions from healthy fish positive for HPR0 virus carrying full-length HPR sampled in a screening program, and a vISAV strain from an ISA outbreak at the same farming site three weeks later, and compared the mutant spectra. As the UDPS data shows the presence of both HE genotypes at both sampling times, and the outbreak strain was unlikely to be directly related to the HPR0 strain, this is the first report of a double infection with HPR0s and vISAVs. For F amplicon reads, mutation frequencies generating L266 codons in screening samples and Q266 codons in outbreak samples were not higher than at any random site. We suggest quasispecies heterogeneity as well as RNA structural properties are linked to transition to virulence. More specifically, a mechanism where selected single point mutations in the full-length HPR alter the RNA structure facilitating single- or sequential deletions in this region is proposed. The data provides stronger support for the deletion hypothesis, as opposed to recombination, as the responsible mechanism for generating the sequence deletions in HE.
Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis

Objective To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). Design This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Outcome measures Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. Results 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: −0.08; 95% credible interval (CrI): −0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; −0.28 to 0.32), degludec (−0.12; −0.42 to 0.20) and premixed insulin (0.26; −0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; −0.31 to 1.71), NPH (−0.76; −1.75 to 0.21) and degludec (−0.63; −1.63 to 0.35), but significantly lower compared with premixed insulin (−1.83; −2.85 to −0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. Conclusions NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.
Prevalence and risk factors for drug resistance among hospitalized tuberculosis patients in Georgia.

BACKGROUND Tuberculosis (TB) control in Georgia follows the World Health Organization-recommended DOTS strategy, and has reached global TB control targets in the treatment of susceptible TB; however, the management of drug-resistant forms of TB still represents a serious problem. A countrywide drug resistance survey (DRS) found that the prevalence of multidrug-resistant TB (MDR-TB) was respectively 6.8% and 27.4% in new and previously treated TB cases. OBJECTIVE To determine the prevalence of and risk factors for drug resistance among TB patients to improve case management and control of drug-resistant TB. METHODS Extensive social, clinical and bacteriological data were collected from patients hospitalized at the National Centre for Tuberculosis and Lung Diseases, Georgia, between 2005 and 2007. RESULTS Of 605 patients, resistance was observed in 491 (81.2%); MDR-TB was found in 261 (43.1%; 51/222 [23%] new cases and 210/383 [55%] previously treated cases), monoresistant TB in 130 (21.5%), poly-resistant TB in 67 (11.1%) and extensively drug-resistant TB in 33 (5.5%). Female sex, living in the densely populated capital, family TB contact and previous TB treatment were associated with risk of MDR-TB. CONCLUSIONS These findings confirm the necessity of improving infection control measures and of standardized treatment for drug-resistant TB patients.
Trisomic pregnancy and the oocyte pool.

BACKGROUND We tested the hypothesis that trisomy risk is increased for women with fewer oocytes (older ovarian age) than other women of the same chronological age. METHODS Our study compared three indicators of ovarian age-number of antral follicles, level of dimeric inhibin B, level of FSH-among women who had trisomic pregnancy losses (n = 54) with those among women who had other losses (24 with other chromosomally abnormal loses, 21 with chromosomally normal losses) or who had chromosomally normal births (n = 65). RESULTS Ovarian age indicators did not differ between women with trisomic spontaneous abortions and the three comparison groups. Compared with live birth controls, adjusting for chronological age, we estimate that, on average, among trisomy cases the geometric means of 1 + follicle count, inhibin B and FSH are about 7.5% higher, 16.6% higher and 5.5% lower, respectively, with all 95% confidence intervals including zero. The sample size was sufficient to detect moderate differences (0.52 standard errors of regression) between trisomy cases and live birth controls. CONCLUSIONS Although our data do not support our hypothesis, they leave open the possibility that changes in follicular development unrelated to the size of the oocyte pool influence abnormal chromosome segregation.
Children's Language Ability and Psychosocial Development: A 29-Year Follow-up Study

OBJECTIVES: Little is known on the psychosocial adult outcomes of children's early language skills or intervening circumstances. The aim of this study was to assess the longitudinal trajectory linking childhood receptive language skills to psychosocial outcomes in later life. METHODS: The study comprised 6941 men and women who participated in a nationally representative Birth Cohort Study. Direct assessment of language skills were made at age 5. The sample was studied again at age 34 to assess psychosocial outcomes and levels of adult mental health. Characteristics of the family environment, individual adjustment, and social adaptation in the transition to adulthood were assessed as potential moderating factors linking early language skills to adult mental health. RESULTS: In early childhood, cohort members with poor receptive language experienced more disadvantaged socioeconomic circumstances than cohort members with normal language skills and showed more behavior and psychosocial adjustment problems in the transition to adulthood. At age 34, cohort members with poor early language skills reported lower levels of mental health than cohort members with normal language. After adjustment for family background and experiences of social adaptation, early language skills maintained a significant and independent impact in predicting adult mental health. CONCLUSIONS: Early receptive language skills are significantly associated with adult mental health as well as psychosocial adjustment during early childhood and in later life. The needs of children with language problems are complex and call for early and continuing provision of educational support and services.
The effect of pre-cooling the injection site on pediatric pain perception during the administration of local anesthesia.

AIM The aim of the study was to evaluate the effect of cooling the soft tissue of injection sites on the pain perceptions of pediatric patients during the administration of local anesthesia for routine dental procedures. METHODS AND MATERIALS A total of 160 children aged 5-6 years were included in the present study. On a random basis, the subjects were allocated to the without ice pretreatment (WIP) group (topical anesthesia + counterstimulation + distraction) or the ice pretreatment (IP) group (cooling + topical anesthesia + counterstimulation + distraction). During the administration of an inferior alveolar nerve block, the children's behavior was assessed using the sound, eye, and motor (SEM) scale. The statistical analysis of data was performed based on the analysis of variance (ANOVA). RESULTS There were no significant differences within the groups between the values of the sound, eye, and motor components for either the WIP or the IP groups (P>0.05). All three components of the SEM in the IP group were consistently lower than the WIP group (P<0.05). Moreover, the SEM value for the WIP group surpassed the IP group (P<0.05). CONCLUSIONS Cooling the site of infiltration block prior to the injection of local anesthesia significantly reduced the pain perceived during injection of local anesthetic agent in pediatric patients. CLINICAL SIGNIFICANCE Pre-cooling of the soft tissues of an injection site prior to the administration of a local anesthetic can minimize the discomfort and anxiety associated with the injection procedure and facilitates the management of pediatric patients during this phase of a dental procedure.
Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury.

BACKGROUND & AIMS Damage to hepatic sinusoidal endothelial cells (SECs) initiates sinusoidal obstruction syndrome (SOS), which is most commonly a consequence of myeloablative chemoirradiation or ingestion of pyrrolizidine alkaloids such as monocrotaline (Mct). This study examines whether SECs are of bone marrow origin, whether bone marrow repair can be a determinant of severity of liver injury, and whether treatment with progenitor cells is beneficial. METHODS Mct-treated female rats received infusion of male whole bone marrow or CD133(+) cells at the peak of sinusoidal injury. The Y chromosome was identified in isolated SECs by fluorescent in situ hybridization. Bone marrow suppression was induced by irradiation of both lower extremities with shielding of the abdomen. RESULTS SECs in uninjured liver have both hematopoietic (CD45, CD33) and endothelial (CD31) markers. After Mct-induced SOS, infusion of bone marrow-derived CD133(+) progenitor cells replaces more than one quarter of SECs. All CD133(+) cells recovered from the SEC fraction after injury are CD45(+). CD133(+)/CD45(+) progenitors also repaired central vein endothelium. Mct suppresses CD133(+)/CD45(+) progenitors in bone marrow by 50% and in the circulation by 97%. Irradiation-induced bone marrow suppression elicited SOS from a subtoxic dose of Mct, whereas infusion of bone marrow during the necrotic phase of SOS nearly eradicates histologic features of SOS. CONCLUSIONS SECs have both hematopoietic and endothelial markers. Bone marrow-derived CD133(+)/CD45(+) progenitors replace SECs and central vein endothelial cells after injury. Toxicity to bone marrow progenitors impairs repair and contributes to the pathogenesis of SOS, whereas timely infusion of bone marrow has therapeutic benefit.
Experimental analysis of inertial effects in the impact testing of polymers

Inertial effects occurring In the impact testing of polymers were experimentally probed by measuring the force versus time response of various materials with two different instrumented impact testers, both with and without anvil. The analysis focused on the first force peak, which was modeled using a mass-spring analog to account for machine-specimen interaction.