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To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs).
Design:
A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods).
Setting:
The study was conducted across 7 geographically diverse ICUs with routine CHG bathing.
Participants:
Adult patients in the medical ICU.
Methods:
CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations.
Results:
We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001).
Conclusions:
Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.
Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.
Methods
This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).
Results
Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.
Conclusion
IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.
Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).
Method
Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).
Results
A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.
Conclusions
Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
Individuals identified as at ultra-high risk (UHR) for psychosis are at risk of poor functional outcome regardless of development of psychotic disorder. Studies examining longitudinal predictors of poor functioning have tended to be small and report only medium-term follow-up data. We sought to examine clinical predictors of functional outcome in a long-term longitudinal study.
Method.
Participants were 268 (152 females, 116 males) individuals identified as UHR 2–14 years previously. A range of clinical and sociodemographic variables were assessed at baseline. Functioning at follow-up was assessed using the Social and Occupational Functioning Assessment Scale (SOFAS).
Results.
Baseline negative symptoms, impaired emotional functioning, disorders of thought content, low functioning, past substance use disorder and history of childhood maltreatment predicted poor functioning at follow-up in univariate analyses. Only childhood maltreatment remained significant in the multivariate analysis (p < 0.001). Transition to psychosis was also significantly associated with poor functioning at long-term follow-up [mean SOFAS score 59.12 (s.d. = 18.54) in the transitioned group compared to 70.89 (s.d. = 14.00) in the non-transitioned group, p < 0.001]. Childhood maltreatment was a significant predictor of poor functioning in both the transitioned and non-transitioned groups.
Conclusions.
Childhood maltreatment and transition to psychotic disorder independently predicted poor long-term functioning. This suggests that it is important to assess history of childhood maltreatment in clinical management of UHR individuals. The finding that transition to psychosis predicts poor long-term functioning strengthens the evidence that the UHR criteria detect a subgroup at risk for schizophrenia.
Individuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term.
Method
A sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset.
Results
The UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876–0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883–0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline.
Conclusions
This study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness.
The ‘at-risk’ criteria are a useful paradigm for investigating the psychological, neurocognitive, neurobiological and genetic risk factors for psychosis, specifically schizophrenia. To date, the primary outcome of interest in at-risk research has been the development of psychotic disorder, whereby patients are categorized as either having ‘transitioned’ or ‘not transitioned’. Despite the acceptance of this dichotomy, it is important to consider that the threshold at which psychotic symptoms progress from attenuated to frank ‘psychotic disorder’ is arbitrary and may be incorrect or meaningless in terms of neurobiological and functional changes associated with psychosis. This has implications for clinical care and the search for markers of schizophrenia. We present recent research suggesting that the term ‘outcome’ needs to be broadened to incorporate non-psychotic diagnoses, functioning and negative symptoms. Shifting the traditional notion of outcome is the future challenge for at-risk research, but the inclusion of outcomes other than psychosis is likely to result in better aetiological models of psychotic illness.
Subclinical psychotic experiences during adolescence may represent liability for developing psychotic disorder. Both coping style and the degree of persistence of psychotic experiences may play a role in the progression to clinical psychotic disorder, but little is known about the causal relationship between the two.
Method
Path modelling was used to examine longitudinal relationships between subclinical positive psychotic experiences and three styles of coping (task-, emotion- and avoidance-oriented) in an adolescent general population sample (n=813) assessed three times in 3 years. Distinct developmental trajectories of psychotic experiences, identified with growth mixture modelling, were compared on the use of these coping styles.
Results
Over time, emotion-oriented coping in general was bi-directionally related to psychotic experiences. No meaningful results were found for task- or avoidance-oriented coping. Females reported using a wider range of coping styles than males, but the paths between coping and psychotic experiences did not differ by gender. Persistence of psychotic experiences was associated with a greater use of emotion-oriented coping, whereas a decrease in experiences over time was associated with an increased use of task-orientated coping.
Conclusions
Emotion-oriented coping is the most important coping style in relation to psychotic experiences, as it may contribute to a ‘vicious cycle’ and is associated with persistence of experiences. In addition, more task-oriented coping may result in a decrease in psychotic experiences. Results suggest that opportunities for intervention may already be present at the level of subclinical psychosis.
The objective of the present study was to investigate the effects of the addition of fibre and the antioxidant N-acetylcysteine (NAC) to fat-rich diets on fetal intrauterine development in rats. A total of eighty virgin female Sprague–Dawley rats were fed a control diet, a high-fat diet (HF), a high-fat and high-fibre diet (HFF) or a high-fat NAC diet until day 19·5 of gestation. Maternal HFF consumption resulted in a significantly higher mean fetal number and placental weight than in the other groups (P < 0·05). The HFF diet significantly abrogated HF-induced decreases in maternal serum and placental superoxide anion and hydroxyl radical scavenging capacities (P < 0·05); partially abrogated HF-induced increases in maternal serum and placental malondialdehyde (MDA) and protein carbonyl concentrations (maternal serum MDA and placental protein carbonyl, P < 0·05); resulted in significantly higher fetal liver total superoxide dismutase (SOD), Cu- and Zn-containing SOD and Mn-containing SOD (Mn-SOD) activities than in the HF group (P < 0·05). Furthermore, mRNA expressions of hypoxia-inducible factor 1-α, thioredoxin 2 and Mn-SOD in fetal liver and Mn-SOD in fetal heart and placental GLUT3 in the HFF group were higher than those in the other groups (P < 0·05). The inclusion of dietary fibre in the HF diet was more effective than NAC supplementation in maintaining maternal serum and placental superoxide anion and hydroxyl radical scavenging capacities close to those of the control. These results suggest that maternal fibre intake during pregnancy is beneficial for fetal intrauterine development possibly through the improvement of maternal, placental and fetal antioxidant capacities and placental nutrient transfer capacity.
The localized surface plasmon resonance (LSPR) is a collective oscillation of conduction electrons confined in metal nanostructures and is largely responsible for surface enhanced spectroscopies. Surface enhanced Raman scattering (SERS) is the best known and most widely applied example of such a surface enhanced spectroscopy. Although closely related and complementary to SERS, surface enhanced infrared absorption (SEIRA) spectroscopy requires more careful engineering of the LSPR of metal nanostructures so that the resonance is within the mid-infrared region. In this study, we demonstrate the use of gold nanorods (Au NR) as a suitable substrate capable of sustaining strong SEIRA spectroscopy. Adsorbate saturated Au NR typically exhibit Fano-type resonances in their SEIRA spectra obtained using reflectance FTIR. Such line asymmetry occurs due to the coupling of the relatively sharp molecular vibrations to the broad continuum of the LSPR resonance of the aggregated Au NR.
The future resolution requirements for the semiconductor industry demand advanced lithographic techniques, such as immersion and extreme ultraviolet (EUV) technologies, which will increase the cost of microelectronics manufacturing. Currently, low-k dielectric materials, which are used as insulating layers between the copper wiring, are indirectly patterned using a set of sacrificial layers and etch processes. The sacrificial layers include a photoresist polymer that must first be imaged prior to transferring the pattern to the underlying layers, including the dielectric layer. In order to reduce the number of processing steps required for semiconductor manufacturing, we have developed a novel photo-patternable low-k dielectric material that (1) eliminates the need for sacrificial layers and (2) reduces the number of wafer processing steps. Silsesquioxane copolymers that undergo acid-catalyzed crosslinking when exposed to 193nm wavelength were synthesized. In addition to the direct photo-patternability, the patterned structures are suitable as a dielectric material with a dielectric constant as low as 2.4, and an appreciable elastic modulus (E > 4.0 GPa). These photo-patternable low-k materials represent a ‘greener' approach to semiconductor manufacturing which has the ability to reduce cost, waste materials, and energy consumption.
The peak energy of photoluminescence (PL) from an undecylenic acid functionalized porous Si demonstrated a large PL red-shift (∼ 75 nm) during 2.5 hours of protein incubation in our previous work. [1] Here we present a similar in-situ PL study of surface functionalized planar Si (Si:COOH). The PL of Si:COOH exhibited a 5 nm red-shift in its peak frequency and an approximately 10% drop in its intensity after incubation in a protein solution. Vibrational spectroscopic characterization was carried out upon the Si:COOH sample for which we observed the PL red-shift. The infrared absorption spectra showed clear evidence of protein adsorption on Si:COOH. This correlation study between the PL peak energy and the vibrational spectrum provided strong evidence that the observed red-shift was due to the formation of semiconductor-protein (Si:COOH:BSA) complexes.
The photoluminescence (PL) intensity of undecylenic acid surface functionalized planar Si (001) was investigated in the presence of colloidal Ag nanoparticles. The acid passivated Si surface has a weak PL at 1125 nm. Upon exposure to a Ag nanoparticle sol, the PL quenched exponentially with a characteristic decay time of ∼ 18 minutes. It is known that the metal mediated charge-transfer process provides a pathway for energy decay and leads to a quenching of luminescence in light emitting material. An in-situ study of the surface passivated Si revealed that the Ag nanoparticle was likely to have come into contact or was sited close enough to the semiconductor surface through adsorption to cause effective PL quenching.
Infrared vibrational spectroscopy in an attenuated total reflection geometry has been employed to investigate the presence of organic and inorganic thin layers on Si-wafer surfaces. Three different processes were compared for surface contaminant removal; microwave plasma, UV-ozone, and a piranha solution cleaning. The CH vibrations at 2928 and 2856 cm-1 characteristic of organic contaminants were monitored before and after each cleaning procedure to determine how well it removed surface contaminants. We found that native oxide removal from the Si surface should only be carried out after a cleaning essay. We observed that surface oxide removal exposed a hydrophobic bare Si surface, attracting organic molecules present in solution or the ambient. A large increase of the CH vibrational signature was observed for a Si wafer after an HF dip. A combination of plasma cleaning followed by UV-Ozone treatment was found the most effective one for Si wafer cleaning. We were able to evaluate the effectiveness of the cleaning methods, hydrogen surface passivation and oxide removal/regrowth.
The mechanical properties of the interfaces in an Al2O3 fiber reinforced β-21S Ti alloy have been evaluated by using fiber pushout tests. The Al2O3 fibers were coated with a refractory metal and Y2O3 which served as a diffusion barrier during the HIPing used to produce the metal matrix composites. By doing fiber pushout tests, the interfacial fracture was found to occur at the interface between the refractory metal and the Y2O3. The interfacial shear strength and interfacial frictional stress were measured to be 323 and 312 ± 2 MPa, respectively. The interfacial frictional stress, which is due to asperity interlocking during the fiber sliding, was correlated to the surface roughness of the coated Al2O3 fiber obtained with the aid of an atomic force microscope. The measured surface roughness of 18.8 ± 2.2 nm was related to the frictional stress through Hutchinson's model.9 The frictional coefficient between the Al2O3 fiber and the Ti matrix is calculated to be 0.32 ± 0.02.