Real-life experience with IV dalbavancin in Canada; results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

OBJECTIVES: We report the use of IV dalbavancin in Canadian patients using data captured by the national CLEAR registry. METHODS: The CLEAR registry uses the web-based data management program, REDCapTM (online survey https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=TPMWJX98HL) to facilitate clinicians entering details associated with their clinical experiences using IV dalbavancin. RESULTS: Data were available for 40 patients. The most common infections treated were acute bacterial skin and skin structure infection (ABSSSI) (62.5% of patients), bone/joint infection (22.5%), bloodstream/vascular infection (7.5%) and endocarditis (5.0%). Dalbavancin was used as directed (75.0%) and empiric therapy (25.0%). MRSA was the most common identified pathogen (70.0%). Dalbavancin was used both in outpatient (e.g., emergency department) (65.0%), and inpatient treatment settings (e.g., hospital ward) (35.0%). Dalbavancin was used due to the convenience of a single dose treatment (77.5%) as well as to facilitate hospital discharge (7.5%). Dalbavancin was primarily used alone (90.0%), and most commonly using a single 1500 mg dose (77.5%). Microbiological success (pathogen eradicated or presumed eradicated) occurred in 88.2% of known cases, while clinical success (cure and/or improvement) occurred in 93.3% of known cases. No adverse events were reported. CONCLUSIONS: In Canada, IV dalbavancin is used as both directed and empiric therapy to treat ABSSSI as well as off-label (bone/joint, bacteremia/vascular, endocarditis, device-related) infections. It is used in both outpatient and inpatient settings due primarily to its convenience as a single-dose treatment regimen and to facilitate early hospital discharge. Dalbavancin use is associated with high microbiological and clinical cure rates along with an excellent safety profile.

Chronic larval and adult honey bee laboratory testing: Which dietary additive should be considered when a test substance is not solubilized in acetone?

Chronic toxicity tests on adult and larval honey bees (Apis mellifera) can require the use of dietary additives (solvents, emulsifiers, adjuvants and viscosifier agents) when the active ingredient of plant protection products cannot be dissolved or does not remain stable and homogeneous within the test diets. Acetone is the widely used and accepted solvent allowed within the international regulatory guidelines, but it can be ineffective in keeping certain compounds in solution and can cause toxicity to adults and larvae. In this publication, we present an evaluation of alternative additives in adult and larval diets. Six dietary additives including five solvents (ethanol, isopropanol, n-propanol, propylene glycol and triethylene glycol) and a viscosifier agent (xanthan gum) at five concentrations along with a negative control and a solvent control (acetone) were investigated at seven laboratories. The safe levels for bees were determined for each of the additives used in the 10-day chronic adult and 22-day chronic larval tests. In the 10-day chronic adult study, ethanol and isopropanol were found to be safe at concentrations ≤ 5.0 %, while xanthan gum can be reliably used at concentrations ≤ 0.1 %. Greater variability across laboratories was observed for N-propanol, propylene glycol, and triethylene glycol and these agents may cause mortality when added to diets at concentrations above 0.25-0.5 %. The safe levels of additives to larval diet in the 22-day chronic larval test had a greater variability and were generally lower than what were observed for adult diet. Our results do not recommend the inclusion of ethanol or n-propanol into the larval diet, and isopropanol, propylene glycol, and triethylene glycol may cause mortality at concentrations above 0.25-0.5 %. Safe levels for xanthan gum were more variable than what was observed for adults, but it can be used reliably at concentrations ≤ 0.05 %. Our analyses conclude that several additives can be integrated successfully in honey bee laboratory bioassays at levels that cause low mortality to adults and larvae.

Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population.

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.

Treatments and Outcomes of Critically Ill Patients with Candida spp. Colonization of the Lower Respiratory Tract in Regina, Saskatchewan.

Background: Among critically ill patients receiving mechanical ventilation, Candida spp. are commonly detected in the lower respiratory tract (LRT). This is generally considered to represent colonization. Objective: To evaluate the use of antifungal treatments and the clinical outcomes of patients with Candida colonization of the LRT. Methods: This retrospective analysis involved consecutive patients admitted to the intensive care unit between April 2016 and May 2021with positive results on Candida spp. testing of LRT samples. Data related to antifungal treatment and clinical outcomes were analyzed descriptively, and multivariable logistic regression was performed. Results: Of 200 patients initially identified, 160 (80%) died in hospital. Antifungal therapy was given to 103 (51.5%) of the patients, with treatment being more likely among those with shock and those who received parenteral nutrition. Mortality was high among patients with positive Candida results on LRT culture, regardless of treatment. Multivariable logistic regression, with adjustment for age, sex, comorbidities, and sequential organ failure assessment (SOFA) score, showed that antifungal treatment was associated with lower odds of death (odds ratio 0.39, 95% confidence interval 0.17-0.87) compared with no treatment (p = 0.021). Conclusions: This study showed higher mortality rates than have been reported previously. Further investigation into the role of antifungal therapy among critically ill patients with Candida spp. colonization is required.

Contexte: Chez les patients gravement malades recevant une ventilation mécanique, les Candida spp. sont fréquemment détectées dans les voies respiratoires inférieures (VRI) ­ une situation généralement considérée comme une colonisation. Objectif: Évaluer l'utilisation d'un traitement antifongique et les résultats cliniques chez les patients présentant une colonisation par Candida dans les VRI. Méthodes: Cette analyse rétrospective portait sur des patients consécutifs de l'unité de soins intensifs ayant obtenu un résultat positif au test de Candida sur les isolats des VRI entre avril 2016 et mai 2021. Les données relatives au traitement antifongique et aux résultats cliniques ont été analysées de manière descriptive, et une régression logistique multivariable a été effectuée. Résultats: Parmi les 200 patients initialement recensés, 160 (80 %) sont décédés à l'hôpital. Une thérapie antifongique a été administrée à 103 (51,5 %) des patients, et le traitement était plus probable chez ceux en état de choc et ceux ayant reçu une nutrition parentérale. Les patients ayant été déclarés positifs pour la Candida dans la culture des VRI présentaient un taux de mortalité élevé, indépendamment du traitement. Une régression logistique multivariable, avec ajustement pour l'âge, le sexe, les comorbidités et le score SOFA (sequential organ failure assessment), a montré que le traitement antifongique était associé à une probabilité de décès réduite (rapport de cotes 0,39; intervalle de confiance à 95 % 0,17­0,87), par rapport à l'absence de traitement (p = 0,021). Conclusions: Cette étude a révélé des taux de mortalité plus élevés que ce qui avait été rapporté précédemment. Une enquête plus approfondie sur le rôle de la thérapie antifongique chez les patients gravement malades présentant une colonisation par Candida spp. est nécessaire.

Common mental disorders in Peruvian immigrant in Chile: a comparison with the host population.

BACKGROUND: The Inner Santiago Health Study (ISHS) aimed to (i) estimate the prevalence of common mental disorders (CMD; i.e. depressive and anxiety disorders) among immigrants of Peruvian origin in Chile; (ii) determine whether such immigrants are at higher risk of CMD when compared with the native-born geographically matched population (i.e. non-immigrants); and (iii) identify factors associated with higher risk of any CMD among this immigrant group. A secondary aim was to describe access to mental health services by Peruvian immigrants meeting criteria for any CMD. METHODS: Findings are based on a population-based cross-sectional household mental health survey of 608 immigrant and 656 non-immigrant adults (18-64 years) residing in Santiago de Chile. Diagnoses of ICD-10 depressive and anxiety disorders and of any CMD were obtained using the Revised Clinical Interview Schedule. The relationships between demographic, economic, psychosocial, and migration-specific predictor variables, and risk of any CMD were analyzed with a series of stepwise multivariate logistic regression models. RESULTS: The one-week prevalence of any CMD was 29.1% (95% CI: 25.2-33.1) among immigrants and 34.7% (95% CI: 30.7-38.7) among non-immigrants. Depending on the statistical model used in the pooled sample, we found the prevalence of any CMD among non-immigrants to be higher (OR=1.53; 95% CI: 1.05-2.25) or similar (OR=1.34; 95% CI: 0.94-19.2) when compared with immigrants. In the multivariate stepwise regression of any CMD in immigrants only, the prevalence was higher for females, those with primary compared to higher education, in debt and exposed to discrimination. Conversely, higher levels of functional social support, sense of comprehensibility, and manageability were associated with a lower risk of any CMD in immigrants. In addition, no differences were observed between immigrants and non-immigrants reporting any CMD in mental health service utilization. CONCLUSION: Our results evidence high levels of current CMD in this immigrant group, particularly amongst women. However, lower adjusted prevalence of any CMD in immigrants compared to non-immigrants was limited to preliminary statistical models, thus failing to provide clear support for a "healthy immigrant effect". The study sheds new light on differences in CMD prevalence by immigrant status in Latin America by examining differential exposure to risk factors in immigrant versus non-immigrant groups.

Concurrent Contribution of Co-contraction to Error Reduction during Dynamic Adaptation of the Wrist.

MRI-compatible robots provide a means of studying brain function involved in complex sensorimotor learning processes, such as adaptation. To properly interpret the neural correlates of behavior measured using MRI-compatible robots, it is critical to validate the measurements of motor performance obtained via such devices. Previously, we characterized adaptation of the wrist in response to a force field applied via an MRI-compatible robot, the MR-SoftWrist. Compared to arm reaching tasks, we observed lower end magnitude of adaptation, and reductions in trajectory errors beyond those explained by adaptation. Thus, we formed two hypotheses: that the observed differences were due to measurement errors of the MR-SoftWrist; or that impedance control plays a significant role in control of wrist movements during dynamic perturbations. To test both hypotheses, we performed a two-session counterbalanced crossover study. In both sessions, participants performed wrist pointing in three force field conditions (zero force, constant, random). Participants used either the MR-SoftWrist or the UDiffWrist, a non-MRI-compatible wrist robot, for task execution in session one, and the other device in session two. To measure anticipatory co-contraction associated with impedance control, we collected surface EMG of four forearm muscles. We found no significant effect of device on behavior, validating the measurements of adaptation obtained with the MR-SoftWrist. EMG measures of co-contraction explained a significant portion of the variance in excess error reduction not attributable to adaptation. These results support the hypothesis that for the wrist, impedance control significantly contributes to reductions in trajectory errors in excess of those explained by adaptation.

[Analysis of Sickness-Related Days of Absence among Soldiers of the German Armed Forces from 2008 to 2018 Part 1: Retrospective Analysis with Comparison to the Statutory Health Insurance System]. / Analyse der krankheitsbedingten Fehltage von Soldatinnen und Soldaten der Bundeswehr von 2008 bis 2018 Teil 1: Retrospektive Analyse mit Vergleich zur Gesetzlichen Krankenversicherung.

BACKGROUND: Sickness-related absences are of particular importance both in the German armed forces and in the civilian sector. THE AIM OF THIS STUDY: was to analyze the incidence of sick leave among soldiers in comparison to the working population covered by the statutory health insurance (SHI) system. METHOD: According to the systematics of the SHI, the key figures on incapacity to work in the period 2008-2018 are calculated in an age- and gender-standardized manner. Likewise, a list of the TOP 20 ICD-10 diagnoses in relation to incapacity to work was determined, and their average annual rates of change were calculated for trend analysis. RESULTS: The annual rate of sick leave among soldiers was between 1.5 and 2.3%, which was lower than that of the SHI (3.1 to 5.0%). The duration of illness (sick days per case) among soldiers was between 9.0-15.6 days per year, compared with 10.9-14.4 days in the SHI system. The sickness frequency (cases per 100 persons) was lower among soldiers (48.2-75.0 cases) than in the SHI (96.8-131.0 cases). Most days of absence among soldiers were due to "respiratory infections (J06)" with 13.2%, "stress reactions (F43)" with 8.7%, "other infectious gastroenteritis and colitis (A09)" with 6.5%, "back pain (M54)" with 4.4% and "depressive episode (F32)" with 4.0% of all days of absence and were comparable to the values in SHI. "Depressive episode (F32)", "injuries (T14)", sreactions (F43)", "respiratory infections (J06)" and "pregnancy complaints (O26)" showed the highest rates of increase of+6.1% to+3.6% of days off work. CONCLUSION: For the first time, it was possible to compare the sickness rate of soldiers with that of the general population in Germany, which may also provide indications for further measures for primary, secondary and tertiary prevention. The lower sickness rate among soldiers compared with the general population is mainly due to a lower incidence of illness, with a similar duration and pattern of illness, but with an overall upward trend. The ICD-10 diagnoses "Depressive episode (F32)," "injuries (T14)," "stress reactions (F43)," "acute upper respiratory tract infections (J06)" and "pregnancy complaints (O26)," which are increasing at an above-average rate in relation to the number of days absent, require further analysis. This approach seems promising, for example, to generate hypotheses and ideas for further improvement of health care.

Effects of mindfulness-based stress reduction on psychological distress in health workers: A three-arm parallel randomized controlled trial.

Mindfulness-based Stress Reduction (MBSR) has shown good efficacy for improving wellbeing in employees experiencing occupational stress. However, comparisons with other interventions, longer-term follow-up, and data from varying sociocultural contexts are lacking. This three-arm, parallel randomised controlled trial (RCT) examined the effects of MBSR on psychological distress in non-physician health workers in direct contact with patients. 105 participants were randomly allocated to either: (1) MBSR (N = 35), (2) Stress Management Course (SMC; N = 34) or (3) wait-list (N = 36). Participants and those assessing outcomes were blinded to group assignment. Participants completed questionnaires pre- and post-intervention and four months after the intervention. Psychological distress was measured using the General Health Questionnaire (GHQ-12) and Outcome Questionnaire (OQ-45). Secondary outcomes included perceived stress, job satisfaction, mindfulness skills and changes in salivary cortisol. 77 participants completed measures post-intervention and 52 at 4-month follow-up. MBSR showed a post-intervention effect in reducing GHQ-12 (ß = -0.80 [SE = 1.58] p < 0.01) and OQ-45 (ß = -0.72, [SE = 5.87] p < 0.05) psychological distress, compared to SMC and in reducing GHQ-12 (ß = -1.30 [SE = 1.38] p < 0.001) and OQ-45 (ß = -0.71, [SE = 5.58] p < 0.01) psychological distress compared to wait-list condition. In our secondary outcome, only MBSR was associated with a decrease in the cortisol awaking response by 23% (p < 0.05). At follow-up, only effects of MBSR on the psychological distress 'social role' subscale (ß = -0.76 [SE = 1.31] p < 0.05) remained significant, compared to SMC. In conclusion, MBSR appears useful in reducing short-term psychological distress in healthcare workers, but these effects were not maintained at follow-up. Trial registration: ISRCTN12039804.

B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS.

A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström's macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88L252P mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88L252P-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88L252P mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88L252P mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM.

Job Insecurity, Sickness Presenteeism and the Moderating Effect of Workplace Health Promotion.

OBJECTIVE: This study examined the relationship between job insecurity and presenteeism, and the role of workplace health promotion as moderator in this association. METHODS: We used data from 9525 employees from the sixth BIBB/BAuA Employment Survey 2012 for the working population in Germany. Data analysis was performed with logistic regressions. RESULTS: Job insecurity was associated with a higher risk of presenteeism, even after adjustment for control factors (OR = 1.25, CI: 1.01-1.53, P < 0.05). Workplace health promotion moderated this relationship: It no longer existed in companies with health promotion. CONCLUSIONS: The results suggest that employees with job insecurity are more likely to work despite feeling ill with the aim of securing their jobs. By establishing workplace health promotion, companies can protect their employees from that behavior in order to avoid negative long-term consequences.

Automobile injury trends in the contemporary fleet: Belted occupants in frontal collisions.

Objective: As vehicle safety technologies and evaluation procedures advance, it is pertinent to periodically evaluate injury trends to identify continuing and emerging priorities for intervention. This study examined detailed injury distributions and injury risk trends in belted occupants in frontal automobile collisions (10 o'clock to 2 o'clock) using NASS-CDS (1998-2015). Methods: Injury distributions were examined by occupant age and vehicle model year (stratified at pre- and post-2009). Logistic regression models were developed to examine the effects of various factors on injury risk (by body region), controlling for delta-V, sex, age, height, body mass index (BMI), vehicle model year (again stratified at 2009). Results: Among other observations, these analyses indicate that newer model year vehicles (model year [MY] 2009 and later) carry less risk of Abbreviated Injury Scale (AIS) 2+ and AIS 3+ injury compared to older model year vehicles, with odds ratios of 0.69 (AIS 2+) and 0.45 (AIS 3+). The largest reductions in risk between newer model year vehicles and older model year vehicles occur in the lower extremities and in the risk of skull fracture. There is no statistically significant change in risk of AIS 3+ rib fracture or sternum injury between model year categories. Females are at greater risk of AIS 2+ and AIS 3+ injury compared to males, with increased risk across most injury types. Conclusions: For belted occupants in frontal collisions, substantial reductions in injury risk have been realized in many body regions in recent years. Risk reduction in the thorax has lagged other body regions, resulting in increasing prevalence among skeletal injuries in newer model year vehicles (especially in the elderly). Injuries also remain common in the arm and hand/wrist for all age ranges studied. These results provide insight into where advances in the field have made gains in occupant protection and what injury types remain to be addressed.

Changes in bacterial diversity and catabolic gene abundance during the removal of dimethylphenol isomers in laboratory-scale constructed wetlands.

Constructed wetlands (CWs) are well-established wastewater treatment technologies and applied for bioremediation of contaminated water. Despite the optimal performance of CWs, the understanding of the bacterial processes in the rhizosphere, where mainly microbial degradation processes take place, is still limited. In the present study, laboratory-scale CWs planted with Juncus effusus and running under controlled conditions were studied in order to evaluate removal efficiency of dimethylphenols (DMPs), also in comparison to an unplanted bed. Next to removal rates, the bacterial community structure, diversity, and distribution, their correlation with physiochemical parameters, and abundance of the phenol hydroxylase gene were determined. As a result, better removal performance of DMP isomers (3,4-, 3,5-, and 2,6-DMP added as singles compounds or in mixtures) and ammonium loads, together with a higher diversity index, bacterial number, and phenol hydroxylase gene abundance in Juncus effusus CW in comparison with the non-planted CW, indicates a clear rhizosphere effect in the experimental CWs. An enhancement in the DMP removal and the recovery of the phenol hydroxylase gene were found during the fed with the DMP mixture. In addition, the shift of bacterial community in CWs was found to be DMP isomer dependent. Positive correlations were found between the bacteria harboring the phenol hydroxylase gene and communities present with 3,4-DMP and 3,5-DMP isomers, but not with the community developed with 2,6-DMP. These results indicate that CWs are highly dynamic ecosystems with rapid changes in bacterial communities harboring functional catabolic genes.

Orientation Control of Block Copolymers Using Surface Active, Phase-Preferential Additives.

Orientation control of thin film nanostructures derived from block copolymers (BCPs) are of great interest for various emerging technologies like separation membranes, nanopatterning, and energy storage. While many BCP compositions have been developed for these applications, perpendicular orientation of these BCP domains is still very challenging to achieve. Herein we report on a new, integration-friendly approach in which small amounts of a phase-preferential, surface active polymer (SAP) was used as an additive to a polycarbonate-containing BCP formulation to obtain perpendicularly oriented domains with 19 nm natural periodicity upon thermal annealing. In this work, the vertically oriented BCP domains were used to demonstrate next generation patterning applications for advanced semiconductor nodes. Furthermore, these domains were used to demonstrate pattern transfer into a hardmask layer via commonly used etch techniques and graphoepitaxy-based directed self-assembly using existing lithographic integration schemes. We believe that this novel formulation-based approach can easily be extended to other applications beyond nanopatterning.

Nanoscale chemical imaging by photoinduced force microscopy.

Correlating spatial chemical information with the morphology of closely packed nanostructures remains a challenge for the scientific community. For example, supramolecular self-assembly, which provides a powerful and low-cost way to create nanoscale patterns and engineered nanostructures, is not easily interrogated in real space via existing nondestructive techniques based on optics or electrons. A novel scanning probe technique called infrared photoinduced force microscopy (IR PiFM) directly measures the photoinduced polarizability of the sample in the near field by detecting the time-integrated force between the tip and the sample. By imaging at multiple IR wavelengths corresponding to absorption peaks of different chemical species, PiFM has demonstrated the ability to spatially map nm-scale patterns of the individual chemical components of two different types of self-assembled block copolymer films. With chemical-specific nanometer-scale imaging, PiFM provides a powerful new analytical method for deepening our understanding of nanomaterials.

Effects of the pattern of glucocorticoid replacement on neural processing, emotional reactivity and well-being in healthy male individuals: study protocol for a randomised controlled trial.

BACKGROUND: Deviation from the physiological glucocorticoid dynamics (circadian and underlying ultradian rhythmicity) is a common characteristic of various neuropsychiatric and endocrine disorders as well as glucocorticoid-based therapeutics. These states may be accompanied by neuropsychiatric symptomatology, suggesting continuous dynamic glucocorticoid equilibrium is essential for brain homeostasis. METHODS/DESIGN: The study consists of two parts. The preliminary stage of the study aims to validate (technically and pharmacologically) and optimise three different patterns of systemic cortisol administration in man. These patterns are based on the combinatory administration of metyrapone, to suppress endogenous cortisol production, and concurrent hydrocortisone replacement. The second, subsequent, core part of the study is a randomised, double-blinded, placebo-controlled, crossover study, where participants (healthy male individuals aged 18-60 years) will undergo all three hydrocortisone replacement schemes. During these infusion regimes, we plan a number of neurobehavioural tests and imaging of the brain to assess neural processing, emotional reactivity and perception, mood and self-perceived well-being. The psychological tests include: ecological momentary assessment, P1vital Oxford Emotional Test Battery and Emotional Potentiated Startle Test, Leeds Sleep Evaluation Questionnaire and the visual working memory task (n-back). The neuroimaging protocol combines magnetic resonance sequences that capture data related to the functional and perfusion status of the brain. DISCUSSION: Results of this clinical trial are designed to evaluate the impact (with possible mechanistic insights) of different patterns of daily glucocorticoid dynamics on neural processing and reactivity related to emotional perception and mood. This evidence should contribute to the optimisation of the clinical application of glucocorticoid-based therapeutics. TRIAL REGISTRATION: UK Clinical Research Network, IRAS Ref: 106181, UKCRN-ID-15236 (23 October 2013).

Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers.

RATIONALE: There is now compelling evidence for a link between enteric microbiota and brain function. The ingestion of probiotics modulates the processing of information that is strongly linked to anxiety and depression, and influences the neuroendocrine stress response. We have recently demonstrated that prebiotics (soluble fibres that augment the growth of indigenous microbiota) have significant neurobiological effects in rats, but their action in humans has not been reported. OBJECTIVES: The present study explored the effects of two prebiotics on the secretion of the stress hormone, cortisol and emotional processing in healthy volunteers. METHODS: Forty-five healthy volunteers received one of two prebiotics (fructooligosaccharides, FOS, or Bimuno®-galactooligosaccharides, B-GOS) or a placebo (maltodextrin) daily for 3 weeks. The salivary cortisol awakening response was sampled before and after prebiotic/placebo administration. On the final day of treatment, participants completed a computerised task battery assessing the processing of emotionally salient information. RESULTS: The salivary cortisol awakening response was significantly lower after B-GOS intake compared with placebo. Participants also showed decreased attentional vigilance to negative versus positive information in a dot-probe task after B-GOS compared to placebo intake. No effects were found after the administration of FOS. CONCLUSION: The suppression of the neuroendocrine stress response and the increase in the processing of positive versus negative attentional vigilance in subjects supplemented with B-GOS are consistent with previous findings of endocrine and anxiolytic effects of microbiota proliferation. Further studies are therefore needed to test the utility of B-GOS supplementation in the treatment of stress-related disorders.

Acute serotonin depletion releases motivated inhibition of response vigour.

RATIONALE: The neurotransmitter serotonin has long been implicated in the motivational control of behaviour. Recent theories propose that the role of serotonin can be understood in terms of an interaction between a motivational and a behavioural activation axis. Experimental support for these ideas, however, has been mixed. OBJECTIVES: In the current study, we aimed to investigate the role of serotonin (5HT) in behavioural vigour as a function of incentive motivation. METHODS: We employed dietary acute tryptophan depletion (ATD) to lower the 5HT precursor tryptophan during the performance of a speeded visual discrimination task. Feedback valence and feedback probability were manipulated independently and cued prior to target onset. On feedback trials, fast correct responses led to either reward or avoidance of punishment, while slow or incorrect responses led to reward omission or punishment. RESULTS: We show that behavioural responding is inhibited under high incentive motivation (i.e. high-feedback probability) at baseline 5HT levels and that lowering these leads to behavioural disinhibition, while leaving accuracy unaffected. Surprisingly, there were no differential effects of motivational valence, with 5HT depletion releasing behavioural inhibition under both appetitive and aversive motivation. CONCLUSIONS: Our findings extend current theories on the role of 5HT in behavioural inhibition by showing that reductions in serotonin lead to increased behavioural vigour only if there is a motivational drive to inhibit behaviour at baseline.

A mechanistic understanding of processing additive-induced efficiency enhancement in bulk heterojunction organic solar cells.

The addition of processing additives is a widely used approach to increase power conversion efficiencies for many organic solar cells. We present how additives change the polymer conformation in the casting solution leading to a more intermixed phase-segregated network structure of the active layer which in turn results in a 5-fold enhancement in efficiency.

Enhanced solid-state order and field-effect hole mobility through control of nanoscale polymer aggregation.

Efficient charge carrier transport in organic field-effect transistors (OFETs) often requires thin films that display long-range order and close π-π packing that is oriented in-plane with the substrate. Although some polymers have achieved high field-effect mobility with such solid-state properties, there are currently few general strategies for controlling the orientation of π-stacking within polymer films. In order to probe structural effects on polymer-packing alignment, furan-containing diketopyrrolopyrrole (DPP) polymers with similar optoelectronic properties were synthesized with either linear hexadecyl or branched 2-butyloctyl side chains. Differences in polymer solubility were observed and attributed to variation in side-chain shape and polymer backbone curvature. Averaged field-effect hole mobilities of the polymers range from 0.19 to 1.82 cm(2)/V·s, where PDPP3F-C16 is the least soluble polymer and provides the highest maximum mobility of 2.25 cm(2)/V·s. Analysis of the films by AFM and GIXD reveal that less soluble polymers with linear side chains exhibit larger crystalline domains, pack considerably more closely, and align with a greater preference for in-plane π-π packing. Characterization of the polymer solutions prior to spin-coating shows a correlation between early onset nanoscale aggregation and the formation of films with highly oriented in-plane π-stacking. This effect is further observed when nonsolvent is added to PDPP3F-BO solutions to induce aggregation, which results in films with increased nanostructural order, in-plane π-π orientation, and field-effect hole mobilities. Since nearly all π-conjugated materials may be coaxed to aggregate, this strategy for enhancing solid-state properties and OFET performance has applicability to a wide variety of organic electronic materials.