Early versus late stage schizophrenia. What markers make the difference?

OBJECTIVES: To identify the psychopathological, cognitive, functional, physical health and inflammatory markers that differentiate between early-stage schizophrenia (ESSCH) and late-stage schizophrenia (LSSCH). METHODS: Cross-sectional, naturalistic study of 104 patients with SCH. The sample was divided in two groups: 35 ESSCH (≤7 years' duration of illness) and 69 LSSCH (>10 years' duration of illness). STATISTICAL ANALYSIS: chi-square test and Student's t-test and ANCOVA (or Quade test) controlling for age, sex, BMI and number of cigarettes/day. Finally, a binomial logistic regression was made. RESULTS: ESSCH show greater negative symptom severity (t = 2.465, p = 0.015), lower levels of IκBα (F = 7.644, p = 0.007), were more frequently classified as normal weight (40% vs 18.8%, p = 0.032) compared with LSSCH. The binomial logistic regression model included age (B = 0.127, p = 0.001) and IκBα (B = 0.025, p = 0.002) and accounted for 38.9% of the variance (model df =7, chi-square =41.841, p < 0.0001). CONCLUSIONS: Age and IκBα are the unique markers that differentiate between ESSCH patients whose duration of illness is less than 7 years and LSSCH patients. These results support the hypothesis of toxicity of episodes and highlight the importance of preventing new episodes.

Inverse association between negative symptoms and body mass index in chronic schizophrenia.

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels.

Regulation of inflammatory pathways in schizophrenia: A comparative study with bipolar disorder and healthy controls.

BACKGROUND: Immune-inflammatory processes have been implicated in schizophrenia (SCH), but their specificity is not clear. MAIN AIM: To identify potential differential intra-/intercellular biochemical pathways controlling immune-inflammatory response and their oxidative-nitrosative impact on SCH patients, compared with bipolar disorder (BD) patients and healthy controls (HC). METHODS: Cross-sectional, naturalistic study of a cohort of SCH patients (n=123) and their controls [BD (n=102) and HC (n=80)]. STATISTICAL ANALYSIS: ANCOVA (or Quade test) controlling for age and gender when comparing the three groups, and controlling for age, gender, length of illness, cigarettes per day, and body mass index (BMI) when comparing SCH and BD. RESULTS: Pro-inflammatory biomarkers: Expression of COX-1 was statistically higher in SCH and BD than HC (P<0.0001; P<0.0001); NFκB and PGE2 were statistically higher in SCH compared with BD (P=0.001; P<0.0001) and HC (P=0.003; P<0.0001); NLRP3 was higher in BD than HC (P=0.005); and CPR showed a gradient among the three groups. Anti-inflammatory biomarkers: BD patients had lower PPARγ and higher 15d-PGJ2 levels than SCH (P=0.005; P=0.008) and HC (P=0.001; P=0.001). Differences between SCH and BD: previous markers of SCH (NFκB and PGE2) and BD (PPARγ and 15d-PGJ2) remained statistically significant and, interestingly, iNOS and COX-2 (pro-inflammatory biomarkers) levels were statistically higher in SCH than BD (P=0.019; P=0.040). CONCLUSIONS: This study suggests a specific immune-inflammatory biomarker pattern for established SCH (NFκB, PGE2, iNOS, and COX-2) that differentiates it from BD and HC. In future, their pharmacological modulation may constitute a promising therapeutic target.

Entanglement of superconducting qubits via acceleration radiation.

We show that simulated relativistic motion can generate entanglement between artificial atoms and protect them from spontaneous emission. We consider a pair of superconducting qubits coupled to a resonator mode, where the modulation of the coupling strength can mimic the harmonic motion of the qubits at relativistic speeds, generating acceleration radiation. We find the optimal feasible conditions for generating a stationary entangled state between the qubits when they are initially prepared in their ground state. Furthermore, we analyse the effects of motion on the probability of spontaneous emission in the standard scenarios of single-atom and two-atom superradiance, where one or two excitations are initially present. Finally, we show that relativistic motion induces sub-radiance and can generate a Zeno-like effect, preserving the excitations from radiative decay.

Digital Quantum Simulation of Minimal AdS/CFT.

We propose the digital quantum simulation of a minimal AdS/CFT model in controllable quantum platforms. We consider the Sachdev-Ye-Kitaev model describing interacting Majorana fermions with randomly distributed all-to-all couplings, encoding nonlocal fermionic operators onto qubits to efficiently implement their dynamics via digital techniques. Moreover, we also give a method for probing nonequilibrium dynamics and the scrambling of information. Finally, our approach serves as a protocol for reproducing a simplified low-dimensional model of quantum gravity in advanced quantum platforms as trapped ions and superconducting circuits.

Quantum chemistry and charge transport in biomolecules with superconducting circuits.

We propose an efficient protocol for digital quantum simulation of quantum chemistry problems and enhanced digital-analog quantum simulation of transport phenomena in biomolecules with superconducting circuits. Along these lines, we optimally digitize fermionic models of molecular structure with single-qubit and two-qubit gates, by means of Trotter-Suzuki decomposition and Jordan-Wigner transformation. Furthermore, we address the modelling of system-environment interactions of biomolecules involving bosonic degrees of freedom with a digital-analog approach. Finally, we consider gate-truncated quantum algorithms to allow the study of environmental effects.

Digital quantum simulation of fermionic models with a superconducting circuit.

One of the key applications of quantum information is simulating nature. Fermions are ubiquitous in nature, appearing in condensed matter systems, chemistry and high energy physics. However, universally simulating their interactions is arguably one of the largest challenges, because of the difficulties arising from anticommutativity. Here we use digital methods to construct the required arbitrary interactions, and perform quantum simulation of up to four fermionic modes with a superconducting quantum circuit. We employ in excess of 300 quantum logic gates, and reach fidelities that are consistent with a simple model of uncorrelated errors. The presented approach is in principle scalable to a larger number of modes, and arbitrary spatial dimensions.

Detection of tick-borne Anaplasma bovis, Anaplasma phagocytophilum and Anaplasma centrale in Spain.

The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes species of medical and veterinary importance. The presence of Anaplasma spp. in ticks from birds, as well as in Haemaphysalis punctata (Ixodida: Ixodidae) specimens collected from cattle and vegetation in northern Spain was investigated. A total of 336 ticks from birds [174 Ixodes frontalis (Ixodida: Ixodidae), 108 H. punctata, 34 Hyalomma marginatum (Ixodida: Ixodidae), 17 Ixodes ricinus (Ixodida: Ixodidae) and three Ixodes spp.], and 181 H. punctata specimens collected from cattle (n = 71) and vegetation (n = 110) were analysed. Anaplasma bovis was detected in five H. punctata, including two from birds (1.9%) and three from vegetation (2.7%). Four I. frontalis (2.3%) (one co-infected with 'Candidatus Midichloria mitochondrii') and one I. ricinus (5.9%) removed from birds, as well as four H. punctata (5.6%) collected from cattle showed Anaplasma phagocytophilum infection. In addition, Anaplasma centrale was found in two H. punctata, one from a cow (1.4%) and the other from vegetation (0.9%). This study represents the first evidence of the presence of A. bovis in European ticks, and reports the first detection of A. bovis and A. centrale in H. punctata, and the first finding of A. phagocytophilum and 'Ca. Midichloria mitochondrii' in I. frontalis.

Fermion-fermion scattering in quantum field theory with superconducting circuits.

We propose an analog-digital quantum simulation of fermion-fermion scattering mediated by a continuum of bosonic modes within a circuit quantum electrodynamics scenario. This quantum technology naturally provides strong coupling of superconducting qubits with a continuum of electromagnetic modes in an open transmission line. In this way, we propose qubits to efficiently simulate fermionic modes via digital techniques, while we consider the continuum complexity of an open transmission line to simulate the continuum complexity of bosonic modes in quantum field theories. Therefore, we believe that the complexity-simulating-complexity concept should become a leading paradigm in any effort towards scalable quantum simulations.

Predictive factors of functional capacity and real-world functioning in patients with schizophrenia.

PURPOSE: This study was performed to identify the predictive factors of functional capacity assessed by the Spanish University of California Performance Skills Assessment (Sp-UPSA) and real-world functioning assessed by the Spanish Personal and Social Performance scale (PSP) in outpatients with schizophrenia. METHODS: Naturalistic, 6-month follow-up, multicentre, validation study. Here, we report data on 139 patients with schizophrenia at their baseline visit. ASSESSMENT: Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Severity (CGI-S), Sp-UPSA and PSP. STATISTICS: Pearson's correlation coefficient (r) was used to determine the relationships between variables, and multivariable stepwise linear regression analyses to identify predictive variables of Sp-UPSA and PSP total scores. RESULTS: Functional capacity: scores on the PSP and PANSS-GP entered first and second at P<0.0001 and accounted for 21% of variance (R(2)=0.208, model df=2, F=15.724, P<0.0001). Real-world functioning: scores on the CGI-S (B=-5.406), PANSS-N (B=-0.657) and Sp-UPSA (B=0.230) entered first, second and third, and accounted for 51% of variance (model df=3, F=37.741, P<0.0001). CONCLUSION: In patients with schizophrenia, functional capacity and real-world functioning are two related but different constructs. Each one predicts the other along with other factors; general psychopathology for functional capacity, and severity of the illness and negative symptoms for real-world functioning. These findings have important clinical implications: (1) both types of functioning should be assessed in patients with schizophrenia and (2) strategies for improving them should be different.

Evaluation of the effectiveness of liraglutide and sitagliptin in type 2 diabetes: a retrospective study in UK primary care.

OBJECTIVE: Type 2 diabetes is a chronic condition that continues to increase in prevalence in the UK. Incretin-based therapies, including liraglutide and sitagliptin, provide adequate blood glucose control. Clinical trials have shown that liraglutide offers greater glycaemic control and body weight reduction in comparison to sitagliptin. We aimed to assess the effectiveness of liraglutide and sitagliptin in routine clinical practice. MATERIALS AND METHODS: We designed and conducted a retrospective database analysis in primary care using the Clinical Practice Research Datalink in the UK. Patients aged ≥ 18 years, diagnosed with type 2 diabetes and prescribed liraglutide or sitagliptin between July 2009 and July 2012, were included in the study. Glycaemic and weight control were investigated 6 months after treatment initiation. RESULTS: A total of 287 liraglutide and 2781 sitagliptin patients were identified. Compared with sitagliptin, liraglutide recipients had greater reductions in HbA1c (%) (-0.90 vs. -0.57, p < 0.01), weight (kg) (-3.78 vs. -1.12, p < 0.001), BMI (kg/m(2) ) (-1.30 vs. -0.39, p < 0.001) and systolic blood pressure (mmHg) (-3.91 vs. -0.39, p < 0.001) after 6 months of treatment. When controlling for potential confounders, liraglutide was more likely than sitagliptin to achieve an HbA1c reduction ≥ 1% (OR = 2.29, 95% CI 1.62-3.25), an HbA1c reduction ≥ 1% and a weight reduction ≥ 3% (OR = 2.99; 95% CI 2.00-4.48) and a target HbA1c < 7% (OR = 2.11; 95% CI 1.45-3.07) after 6 months of treatment. CONCLUSIONS: Clinical trials show superior glycaemic control and weight reduction with liraglutide compared with sitagliptin. This finding is reflected in routine clinical practice in the UK.

Spanish adaptation and validation of the Brief Negative Symptoms Scale.

Negative symptoms prevalent in schizophrenia are associated with poor outcome. Developing new instruments to identify new treatments was highlighted at the NIMH-MATRICS Consensus Development Conference on Negative Symptoms. The new Brief Negative Symptoms scale (BNSS) demonstrated strong psychometric properties, but there is a need for validating it in non-English languages. A multi-center study was conducted to validate the Spanish version of the BNSS (BNSS-Sp) in 20 schizophrenia patients, following the original BNSS validation methodology. We found strong inter-rater, test-retest and internal consistency properties (for the total BNSS-Sp, intraclass correlation coefficient=0.97, Pearson's correlation coefficient r=0.95 (p<0.001), Cronbach's alpha=0.98).

Advances in electronic surveillance for healthcare-associated infections in the 21st Century: a systematic review.

BACKGROUND: Traditional methodologies for healthcare-associated infection (HCAI) surveillance can be resource intensive and time consuming. As a consequence, surveillance is often limited to specific organisms or conditions. Various electronic databases exist within the healthcare setting and may be utilized to perform HCAI surveillance. AIM: To assess the utility of electronic surveillance systems for monitoring and detecting HCAI. METHODS: A systematic review of published literature on surveillance of HCAI was performed. Databases were searched for studies published between January 2000 and December 2011. Search terms were divided into infection, surveillance and data management terms, and combined using Boolean operators. Studies were included for review if they demonstrated or proposed the use of electronic systems for HCAI surveillance. FINDINGS: In total, 44 studies met the inclusion criteria. For the majority of studies, emphasis was on the linkage of electronic databases to provide automated methods for monitoring infections in specific clinical settings. Twenty-one studies assessed the performance of their method with traditional surveillance methodologies or a manual reference method. Where sensitivity and specificity were calculated, these varied depending on the organism or condition being surveyed and the data sources employed. CONCLUSIONS: The implementation of electronic surveillance was found to be feasible in many settings, with several systems fully integrated into hospital information systems and routine surveillance practices. The results of this review suggest that electronic surveillance systems should be developed to maximize the efficacy of abundant electronic data sources existing within hospitals.

Risk factors for healthcare-associated urinary tract infection and their applications in surveillance using hospital administrative data: a systematic review.

BACKGROUND: Healthcare-associated urinary tract infections (HCA UTI) account for a large proportion of hospital infections, with recently launched surveillance in the UK focusing on reducing catheter-associated urinary tract infections. However, a wealth of administrative information already collected routinely by hospitals is currently not used to its maximum potential for surveillance. AIM: To quantify the evidence base of HCA UTI risk factors and to determine their potential for shaping and informing innovative surveillance tools using local hospital data. METHODS: A systematic literature review was undertaken to find established risks for HCA UTI. Population-attributable risk percentages (PAR%) were calculated for these risk factors, generating a hierarchy of risks. Administrative hospital data were subsequently interrogated for these quantified risks. FINDINGS: Over 30% of the risk factors identified from the systematic literature review were independent predictors of infection. The highest PAR% was associated with urinary catheterization, with the calculation that 79.3% of UTI would be prevented if catheterization was not performed. PAR% calculations were performed for 60% of the independent predictors for HCA UTI. Sixty-five percent of the identified independent risk factors were found to be coded within the administrative hospital dataset, including urinary catheterization. CONCLUSION: This work has quantified established HCA UTI risks and demonstrates that there is potential for more effective use of administrative hospital data for risk monitoring and surveillance of HCA UTI.

Data linkage between existing healthcare databases to support hospital epidemiology.

Enhancing the use of existing datasets within acute hospitals will greatly facilitate hospital epidemiology, surveillance, the monitoring of a variety of processes, outcomes and risk factors, and the provision of alert systems. Multiple overlapping data systems exist within National Health Service (NHS) hospitals in the UK, and many duplicate data recordings take place because of the lack of linkage and interfaces. This results in hospital-collected data not being used efficiently. The objective was to create an inventory of all existing systems, including administrative, management, human resources, microbiology, patient care and other platforms, to describe the data architecture that could contribute valuable information for a hospital epidemiology unit. These datasets were investigated as to how they could be used to generate surveillance data, key performance indicators and risk information that could be shared at board, clinical programme group, specialty and ward level. An example of an output of this integrated data platform and its application in influenza resilience planning and responsiveness is described. The development of metrics for staff absence and staffing levels may also be used as key indicators for risk-monitoring for infection prevention. This work demonstrates the value of such a data inventory and linkage and the importance of more sophisticated uses of existing NHS data, and innovative collaborative approaches to support clinical care, quality improvement, surveillance, emergency planning and research.

A novel field-based approach to validate the use of network models for disease spread between dairy herds.

The introduction of a centralized system for recording cattle movements in the UK has provided a framework for network-based models for disease spread. However, there are many types of non-reportable contacts between farms which may play a role in disease spread. The lack of real pathogen data with which to test network models makes it difficult to assess whether reported data adequately captures the risk-potential network between farms and improves the accuracy of disease forecasts. A novel multi-disciplinary approach is described whereby network-based models, built upon reported cattle movements and non-reportable local contacts between study farms, are parameterized using field data on bovine Staphylococcus aureus strains. Reported cattle movements were found to play a role in strain spread between farms, but other contacts via farm visitors were also correlated with strain distribution, suggesting that parameterizing contact networks using cattle-tracing data alone may not adequately capture the disease dynamics.

Sexual expression and genetic diversity in populations of Cryptogramma crispa (Pteridaceae).

The reproductive biology of Cryptogramma crispa, a tetraploid species with a broad circumboreal and alpine distribution, growing mainly in siliceous boulder fields and crevices, was studied in the laboratory by growing gametophytes in plates with both solidified agar media and sterilized soil. In addition, an electrophoretic study of isozymes was carried out on frond samples from five natural populations, as an additional source of evidence concerning the breeding system and the genetic structure of sporophyte populations. Populations throughout the Iberian range of the species were selected for this study, and a Scottish population was included to represent plants from outside our local area and ecology. The morphological development of gametophytes is of the Adiantum type. All multispore cultures developed into a bigametophytic system, consisting in most cases of male and female prothalli. This pattern of sexual expression provides evidence for outcrossing as the main breeding system in this species. Moreover, there is good evidence that the species possesses an antheridiogen system to promote outcrossing. The long time needed by gametophytes to produce gametangia, and afterwards to fertilize and produce sporophytes, might be the primary reason why so few young sporophytes are found in the wild. The values of the percentage of polymorphic loci and the similarity levels obtained from the isozyme analyses indicate a level of genetic variability that would be expected in an outcrossing species. All these characteristics are usually associated with diploid fern species rather than polyploid species.