Prior Conditioning Research Articles

Optimizing sludge treatment and cutting costs

Operating costs in a sewage plant depend on the prior chemical conditioning (coagulation, flocculation, liming) of sludge. Here we look at two devices from the Institut de la Filtration et des Techniques Séparatives (IFTS) which help optimize flocculation and adjust sludge conditions.ito reduce treatment process costs.

A Phase I/II Study of Escalating Doses of Bortezomib in Conjunction with High-Dose Melphalan as a Conditioning Regimen for Salvage Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma

Escalating doses of bortezomib with high-dose melphalan was evaluated as as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory multiple myeloma (MM). MM patients with less than a partial remission (PR) (or 50% reduction) compared to their pretransplantation paraprotein parameters after a prior ASCT with melphalan conditioning, or who were in relapse after a prior autologous transplantation, were eligible for study. Bortezomib was dose escalated in steps of 1, 1.3, and 1.6 mg/m2 (3 × 3 design) on days −4 and −1 before transplantation with melphalan 200 mg/m2 given on day −2. Thirty-two patients were enrolled: 12 in the phase I dose escalation phase and an additional 20 in phase II to gain additional experience with the regimen. Twenty-four (75%) patients were Durie Salmon stage III, and 12 (37.5%) had >2 prior lines of therapy. The overall response rate (≥PR) was 44% with 22% complete remission. Two-year overall survival and progression-free survival were 76% and 39%, respectively, with a median follow-up of 31.7 months. The most common grade 3 and 4 nonhematologic adverse events were neutropenic fever (25%), nausea (18.8%), and mucositis (9.4%). Serious adverse events included intensive care unit admission (9.4%), seizure (3.1%), prolonged diarrhea (3.1%), and Guillain-Barre syndrome (3.1%). Two patients (6%) died of sepsis. There was no emergent peripheral neuropathy nor increase in any pre-existing peripheral neuropathy. The addition of bortezomib to melphalan as conditioning for salvage ASCT was well tolerated. More importantly, it can provide durable remission for patients who have a suboptimal response to prior single-agent melphalan conditioning for ASCT, without requiring a reduction in the dose of melphalan. Larger randomized prospective studies to determine the effect of combination conditioning are being conducted.

De l’Université du rétablissement

Objectives Located at the heart of a mental health university institute in Montreal, Canada, the University of Recovery (UR) is a peer-run agency of service users who came together as a private non-profit organization to promote their experiential knowledge in science and public health, and to transform the academic milieu as an inclusive work environment conducive to recovery and full citizenship. UR students can thus have access to scientific conferences and classes on various topics and invite scientists or other professionals to further discuss new discoveries and techniques, and possible ways of improving healthcare from a patients' and service users' perspective. Our conversation with a scientist specialized in obsessive-compulsive disorders triggered this collective reflection on neuroimaging in terms of psychiatric diagnoses, prognoses, recovery opportunities and meta-cognition.Method At the core of the UR as a therapeutic education program is the Projet Citoyen, an adaptation and a transposition in Montreal of the Yale Citizens Project, which has been developed in New Haven, USA, over the past fifteen years. The Projet Citoyen is comprised of four main components: bi-weekly group discussions, individualized peer support, involvement and practicum in the community, and participation in public events and debates. UR students therefore evolve in the academic and scientific milieu, here regarded as a translational community and human laboratory towards social inclusion and full citizenship. UR students can be involved as auxiliaries of medical training to always promote and illustrate recovery opportunities when psychiatric 'dysfunctions' or 'disorders' are the topics of a medical class. In April 2016, UR students invited Dr Marc Lavoie to discuss is work on obsessive-compulsive disorders (OCD). The content of this group discussion is herein reported.Results UR students learned, among other things, that neuroimaging can be used to identify patterns of brain reactions to various stimuli and situations, reactions that can be different from one psychiatric condition to another and to the rest of the 'normal' population. For example, bright red, green, or blue shades of color can show an over-activation of the thalamus for persons with OCD. This difference can be indicative of a so-called cognitive impairment, with some people reacting more 'emotionally' to an image than other persons for whom the reaction would imply parts of the brain which are normally rather associated to 'rational' thinking (e.g.: the cerebral cortex). Such a difference, when it appears through a neuroimaging technique like EEG or MRI, does not lead to the enunciation of a particular diagnosis for an individual, but can give some complementary indications to be used in conjunction with other observations and can inform the choice for a therapeutic approach. Cognitive Behavioural Therapy, for instance, has been statistically shown to be associated with anatomic changes in the human brain. Through some quite spectacular images of parts and subparts of the brain in action, UR students were able to admire all this beautiful neurodiversity. Then we discussed the concept of neuroplasticity: we now know that many aspects of the brain remain changeable or "plastic" even into adulthood, which contrasts with the previous common consensus that the human brain develops during childhood, then remains at once unchangeable afterward and "static."Conclusion Diverse neurological conditions appear as a result of normal variations in the human genome and in affect, the concepts of neurodiversity and of neuroplasticity go much beyond the prevailing prior conceptual conditioning of neurological differences as being inherently pathological and an irreversible "error of Mother Nature." There may be behaviors that cannot be controlled through rational thought, but rather emerge based on prior conditioning from the environment and other external and/or internal stimuli, and a psychotherapy could then consist of recognizing this conditioning and learning how to think and react differently to a triggering stimulus. The University of Recovery is thus first and foremost a principle of mutuality among its members - the students in recovery - who are allied through self-help as a basis for metacognitive therapeutic education.

Image processing for identification and quantification of filamentous bacteria in in situ acquired images.

BackgroundIn the activated sludge process, problems of filamentous bulking and foaming can occur due to overgrowth of certain filamentous bacteria. Nowadays, these microorganisms are typically monitored by means of light microscopy, commonly combined with staining techniques. As drawbacks, these methods are susceptible to human errors, subjectivity and limited by the use of discontinuous microscopy. The in situ microscope appears as a suitable tool for continuous monitoring of filamentous bacteria, providing real-time examination, automated analysis and eliminating sampling, preparation and transport of samples. In this context, a proper image processing algorithm is proposed for automated recognition and measurement of filamentous objects.MethodsThis work introduces a method for real-time evaluation of images without any staining, phase-contrast or dilution techniques, differently from studies present in the literature. Moreover, we introduce an algorithm which estimates the total extended filament length based on geodesic distance calculation. For a period of twelve months, samples from an industrial activated sludge plant were weekly collected and imaged without any prior conditioning, replicating real environment conditions.ResultsTrends of filament growth rate—the most important parameter for decision making—are correctly identified. For reference images whose filaments were marked by specialists, the algorithm correctly recognized 72 % of the filaments pixels, with a false positive rate of at most 14 %. An average execution time of 0.7 s per image was achieved.ConclusionsExperiments have shown that the designed algorithm provided a suitable quantification of filaments when compared with human perception and standard methods. The algorithm’s average execution time proved its suitability for being optimally mapped into a computational architecture to provide real-time monitoring.

Incorporation of low energy activated nitrogen onto HOPG surface: Chemical states and thermal stability studies by in-situ XPS and Raman spectroscopy

In this paper we report the chemical states analysis of activated nitrogen incorporated highly oriented pyrolytic graphite (HOPG) surface under well-controlled conditions. Nitrogen incorporation is carried out by two different processes: an indirect RF nitrogen plasma and low energy (1keV) N2+ implantation. Bonding configuration, concentration and thermal stability of the incorporated nitrogen species by aforesaid processes are systematically compared by in-situ X-ray photoelectron spectroscopy (XPS). Relatively large concentration of nitrogen is incorporated onto RF nitride HOPG surface (16.2 at.%), compared to N2+ implanted HOPG surface (7.7 at.%). The evolution of N 1s components (N1, N2, N3) with annealing temperature is comprehensively discussed, which indicates that the formation and reorganization of local chemical bonding states are determined by the process of nitridation and not by the prior chemical conditioning (i.e., amorphization or hydrogenation) of the HOPG surface. A combined XPS and Raman spectroscopy studies revealed that N2+ implantation process resulted in a high level of defects to the HOPG surface, which cannot be annealed-out by heat treatment up to 1000°C. On the other hand, the RF nitrogen plasma process did not produce a high level of surface defects, while incorporating nearly the same amount of stable nitrogen species.

Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplantation: Subanalysis Data from an Open-Label, Phase III, Randomized Trial

Introduction Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of conditioning for hematopoietic stem cell transplantation (HSCT) and is associated with patient and transplant-related risk factors, such as prior therapies, underlying diagnoses, and conditioning regimen. Unpredictable in its occurrence and severity, VOD/SOS is clinically characterized by painful hepatomegaly, hyperbilirubinemia, ascites, and weight gain. Overall estimated prevalence is 14% post-HSCT, while rates in some high-risk populations (eg, osteopetrosis or prior gemtuzumab ozogamicin) are >60% (Wadleigh M et al. Blood . 2003;102:1578-82; Corbacioglu S et al. Bone Marrow Transplant . 2006;38:547-53). Evidence suggests that defibrotide stabilizes endothelial cells, with direct and endothelial-cell mediated restoration of the thrombo-fibrinolytic balance. Defibrotide is approved in the European Union for the treatment of severe hepatic VOD/SOS in patients receiving HSCT, and is available in the United States through an expanded-access study. In a previously reported randomized clinical trial, defibrotide prophylaxis for VOD/SOS in high-risk pediatric patients undergoing HSCT reduced the overall incidence of VOD/SOS by day +30 post-HSCT. Here we report novel subgroup analyses of VOD/SOS incidence from this trial in patients with specific VOD/SOS risk factors at baseline. Methods This was a phase 3, multicenter, open-label, randomized, controlled trial in patients aged 5% weight gain. Patients were randomized to standard care with or without defibrotide prophylaxis dosed at 25 mg/kg/day in 4 divided infusions of 6.25 mg/kg. Osteopetrosis was a stratification variable. Defibrotide began the same day as HSCT conditioning and continued for 30 days post-HSCT, or ≥14 days for patients discharged from hospital before day +30 post-HSCT. Control patients who developed VOD/SOS received defibrotide treatment. The primary endpoint was incidence of VOD/SOS at day +30 post-HSCT. Results The intent-to-treat population included 356 patients: 180 randomized to defibrotide prophylaxis and 176 in the control group. Mean (SD) age was 6.6 (5.3) years, and 40.7% of patients were female. Demographic and clinical characteristics, including VOD/SOS risk factors (Table), were well-matched in the defibrotide and control groups. The most common risk factors among all patients were conditioning with busulfan and melphalan (58%), preexisting liver disease (27%), and second myeloablative transplantation (13%). VOD/SOS occurred by day +30 post-HSCT in 22 (12%) patients in the defibrotide prophylaxis group vs 35 (20%) patients in the control group. For the stratification variable, osteopetrosis, rates of VOD/SOS were 14% in the defibrotide prophylaxis arm and 67% in the control arm (Table). Differences in rates of VOD/SOS were lowest for adrenoleukodystrophy (no cases) and prior abdominal irradiation (11% vs 13%, respectively) (Table). Conclusions Across risk-factor subgroups, the rate of VOD/SOS was lower in patients receiving defibrotide compared with controls (except adrenoleukodystrophy: no VOD/SOS in either group). In particular, rates of VOD/SOS by day +30 were reduced by ≥50% in the defibrotide arm vs the control arm among patients with osteopetrosis, hemophagocytic lymphohistiocytosis, second myeloablative transplantation, and prior gemtuzumab treatment. Although the total numbers of patients with these risk factors were small, these between-group differences are of clinical interest and should be further explored. | Risk Factor | Defibrotide (n=180) | Control (n=176) | | ------------------------------------ | ----------------------------------------------- | --------------- | ----------------------------------------------- | | Total n | VOD/SOS incidence (n=22; 12.2%) n (%*) | Total n | VOD/SOS incidence (n=35; 20.0%) n (%*) | | Adrenoleukodystrophy | 1 | 0 (0) | 1 | 0 (0) | | Osteopetrosis | 7 | 1 (14) | 6 | 4 (67) | | Prior abdominal irradiation | 9 | 1 (11) | 8 | 1 (13) | | Hemophagocytic lymphohistiocytosis | 10 | 0 (0) | 15 | 6 (40) | | Prior gemtuzumab | 11 | 2 (18) | 5 | 2 (40) | | Allogeneic HSCT for leukemia | 17 | 2 (12) | 11 | 2 (18) | | Second myeloablative transplantation | 25 | 2 (8) | 23 | 4 (17) | | Pre-existing liver disease | 41 | 6 (15) | 54 | 12 (22) | | Busulfan/melphalan conditioning | 106 | 15 (14) | 99 | 17 (17) | * *Percent of patients with VOD/SOS. Table. Support: Jazz Pharmaceuticals Disclosures Corbacioglu: Gentium S.p.A.: Consultancy, Honoraria. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Bader: Amgen: Consultancy; Medac: Other: Institutional grants; Neovii: Other: Institutional grants; Riemser: Other: Institutional grants; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy.

Impact of Prior Conditioning Intensity on Outcomes after Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation for AML and MDS: A Single-Center Retrospective Analysis

Impact of Prior Conditioning Intensity on Outcomes after Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation for AML and MDS: A Single-Center Retrospective Analysis

4. Muscle excitability in Myotonic Dystrophy type 1

The measurement of muscle velocity recovery cycles (MVRCs) is now an established technique that has been used to determine the excitability properties of skeletal muscle in vivo in a variety of myopathic conditions. Patterns of change in the velocity of muscle action potentials generated by different temporal combinations of prior conditioning impulses sensitively reflect membrane polarization and the function of T-tubules. Further, studies in myotonia congenita (MC) have yielded fundamental insights into the function of the muscle chloride channel itself, in both MC and in general. Myotonic dystrophy type 1 (DM1) is an inherited disorder of RNA splicing that alters the transcription of muscle chloride channels, thereby affecting function and causing myotonia. However, a number of other genes encoding muscle proteins that may determine excitability are similarly mis-spliced. We studied the excitability properties of skeletal muscle in DM1, aiming to gain further insight into the determinants of muscle membrane dysfunction in this disorder. Control studies were established and a cohort of DM1 compared to these. The results of the studies will be presented.

Comparison of resin bonding improvements to zirconia between one-bottle universal adhesives and tribochemical silica coating, which is better?

ObjectivesTo evaluate the bonding of resin-cement to yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) via silica coating followed by silanization, and three one-bottle universal adhesives, with or without prior conditioning using a zirconia primer. MethodsY-TZP specimens (n=160) were conditioned by tribochemical silica coating and silanization (CS), or alumina sandblasting with one of the following MDP containing adhesives or primers: Z-Prime Plus™ (zirconia primer, ZP), Single Bond Universal™ (SU), Clearfil Universal Bond™ (CU) or All-Bond Universal™ (AU). Additionally, some specimens (ZPSU, ZPCU and ZPAU) received Z-Prime Plus™ followed by one of the three adhesives. After 24h water storage and “aging” (20,000 thermocycles plus additional 40-day water storage), shear bond strength (SBS) was measured. Fourier-transform infrared spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) were employed for characterization of the chemical bonds between the primer/adhesives and the zirconia. Thermodynamic calculations were used to examine the hydrolytic stability between the MDP-zirconia chemical bonds and the SiO2-silane chemical bonds. ResultsThe CS and ZPCU groups showed higher SBS than the other six groups. There were no significant pairwise differences amongst ZP, SU and ZPSU, or amongst ZP, AU and ZPAU. Aging led to significantly decreased SBS for all groups except CS and ZPCU. There was no statistically significant interaction between surface treatment and aging. XPS determined the chemical bonds between MDP and zirconia. FTIR showed similar shifts in characteristic phosphate peaks for all the primer and/or adhesive groups. Result of thermodynamic calculation showed that equilibrium constant of SiO2-silane system is much larger than the one of MDP-tetragonal phase zirconia system. SignificanceThe application of one-bottle universal adhesives after alumina sandblasting is an alternative to tribochemical silica coating with silanization for bonding to zirconia, while bonding between resin and Y-TZP is more susceptible to hydrolysis when zirconia primer or one-bottle universal adhesive is used.

Skeletal muscle conditioning may be an effective rehabilitation intervention preceding functional electrical stimulation cycling.

In our recent effort, we introduced a submaximal index that utilized ventilatory efficiency relative to CO2 production (VE/CO2) to evaluate the cardiovascular effectiveness to functional electrical stimulation lower-extremity cycling (FES-LEC) in persons with spinal cord injury (SCI) (Gorgey and Lawrence, 2016). When compared to the resting state, we found that an acute bout of FES-LEC resulted in increased ventilation during exercise and a significant decrease of approximately 22% in the VE/CO2 ratio, suggesting that this ratio could be utilized to monitor the cardiovascular response during submaximal FES-LEC in the SCI population. The study demonstrated that a potential limitation to the FES-LEC application is a heavy reliance on carbohydrate storage as a main source of substrate utilization. Reliance on carbohydrate utilization, transformation to fast-twitch fibers following SCI and random muscle recruitment are likely to introduce rapid muscle fatigue during FES-LEC applications. This may limit oxygen uptake and outcomes regarding cardiovascular profile. In this perspective, we propose that skeletal muscle conditioning via surface neuromuscular electrical stimulation (NMES) may be an essential rehabilitation intervention to improve the outcomes of FES-LEC applications.

Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplantation: Subanalysis Data from an Open-Label, Phase III, Randomized Trial

Introduction Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of conditioning for hematopoietic stem cell transplantation (HSCT) and is associated with patient and transplant-related risk factors, such as prior therapies, underlying diagnoses, and conditioning regimen. Unpredictable in its occurrence and severity, VOD/SOS is clinically characterized by painful hepatomegaly, hyperbilirubinemia, ascites, and weight gain. Overall estimated prevalence is 14% post-HSCT, while rates in some high-risk populations (eg, osteopetrosis or prior gemtuzumab ozogamicin) are >60% (Wadleigh M et al. Blood. 2003;102:1578-82; Corbacioglu S et al. Bone Marrow Transplant. 2006;38:547-53). Evidence suggests that defibrotide stabilizes endothelial cells, with direct and endothelial-cell mediated restoration of the thrombo-fibrinolytic balance. Defibrotide is approved in the European Union for the treatment of severe hepatic VOD/SOS in patients receiving HSCT, and is available in the United States through an expanded-access study. In a previously reported randomized clinical trial, defibrotide prophylaxis for VOD/SOS in high-risk pediatric patients undergoing HSCT reduced the overall incidence of VOD/SOS by day +30 post-HSCT. Here we report novel subgroup analyses of VOD/SOS incidence from this trial in patients with specific VOD/SOS risk factors at baseline. Methods This was a phase 3, multicenter, open-label, randomized, controlled trial in patients aged <18 years, undergoing myeloablative conditioning before allogeneic or autologous HSCT, with ≥1 risk factor for VOD/SOS. VOD/SOS was diagnosed according to modified Seattle criteria plus >5% weight gain. Patients were randomized to standard care with or without defibrotide prophylaxis dosed at 25 mg/kg/day in 4 divided infusions of 6.25 mg/kg. Osteopetrosis was a stratification variable. Defibrotide began the same day as HSCT conditioning and continued for 30 days post-HSCT, or ≥14 days for patients discharged from hospital before day +30 post-HSCT. Control patients who developed VOD/SOS received defibrotide treatment. The primary endpoint was incidence of VOD/SOS at day +30 post-HSCT. Results The intent-to-treat population included 356 patients: 180 randomized to defibrotide prophylaxis and 176 in the control group. Mean (SD) age was 6.6 (5.3) years, and 40.7% of patients were female. Demographic and clinical characteristics, including VOD/SOS risk factors (Table), were well-matched in the defibrotide and control groups. The most common risk factors among all patients were conditioning with busulfan and melphalan (58%), preexisting liver disease (27%), and second myeloablative transplantation (13%). VOD/SOS occurred by day +30 post-HSCT in 22 (12%) patients in the defibrotide prophylaxis group vs 35 (20%) patients in the control group. For the stratification variable, osteopetrosis, rates of VOD/SOS were 14% in the defibrotide prophylaxis arm and 67% in the control arm (Table). Differences in rates of VOD/SOS were lowest for adrenoleukodystrophy (no cases) and prior abdominal irradiation (11% vs 13%, respectively) (Table). Conclusions Across risk-factor subgroups, the rate of VOD/SOS was lower in patients receiving defibrotide compared with controls (except adrenoleukodystrophy: no VOD/SOS in either group). In particular, rates of VOD/SOS by day +30 were reduced by ≥50% in the defibrotide arm vs the control arm among patients with osteopetrosis, hemophagocytic lymphohistiocytosis, second myeloablative transplantation, and prior gemtuzumab treatment. Although the total numbers of patients with these risk factors were small, these between-group differences are of clinical interest and should be further explored. Table. Risk Factor Defibrotide (n=180) Control (n=176) Total n VOD/SOS incidence (n=22; 12.2%) n (%*) Total n VOD/SOS incidence (n=35; 20.0%) n (%*) Adrenoleukodystrophy 1 0 (0) 1 0 (0) Osteopetrosis 7 1 (14) 6 4 (67) Prior abdominal irradiation 9 1 (11) 8 1 (13) Hemophagocytic lymphohistiocytosis 10 0 (0) 15 6 (40) Prior gemtuzumab 11 2 (18) 5 2 (40) Allogeneic HSCT for leukemia 17 2 (12) 11 2 (18) Second myeloablative transplantation 25 2 (8) 23 4 (17) Pre-existing liver disease 41 6 (15) 54 12 (22) Busulfan/melphalan conditioning 106 15 (14) 99 17 (17) *Percent of patients with VOD/SOS. Support: Jazz Pharmaceuticals Disclosures Corbacioglu: Gentium S.p.A.: Consultancy, Honoraria. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Bader:Amgen: Consultancy; Medac: Other: Institutional grants; Neovii: Other: Institutional grants; Riemser: Other: Institutional grants; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy.

Metaplastic Regulation of CA1 Schaffer Collateral Pathway Plasticity by Hebbian MGluR1a-Mediated Plasticity at Excitatory Synapses onto Somatostatin-Expressing Interneurons

Cortical GABAergic interneurons represent a highly diverse neuronal type that regulates neural network activity. In particular, interneurons in the hippocampal CA1 oriens/alveus (O/A-INs) area provide feedback dendritic inhibition to local pyramidal cells and express somatostatin (SOM). Under relevant afferent stimulation patterns, they undergo long-term potentiation (LTP) of their excitatory synaptic inputs through multiple induction and expression mechanisms. However, the cell-type specificity of these different forms of LTP and their specific contribution to the dynamic regulation of the CA1 network remain unclear. Here we recorded from SOM-expressing interneurons (SOM-INs) in the O/A region from SOM-Cre-Ai3 transgenic mice in whole-cell patch-clamp. Results indicate that, like in anatomically identified O/A-INs, theta-burst stimulation (TBS) induced a Hebbian form of LTP dependent on metabotropic glutamate receptor type 1a (mGluR1a) in SOM-INs, but not in parvalbumin-expressing interneurons, another mainly nonoverlapping interneuron subtype in CA1. In addition, we demonstrated using field recordings from transgenic mice expressing archaerhodopsin 3 selectively in SOM-INs, that a prior conditioning TBS in O/A, to induce mGluR1a-dependent LTP in SOM-INs, upregulated LTP in the Schaffer collateral pathway of pyramidal cells. This effect was prevented by light-induced hyperpolarization of SOM-INs during TBS, or by application of the mGluR1a antagonist LY367385, indicating a necessity for mGluR1a and SOM-INs activation. These results uncover that SOM-INs perform an activity-dependent metaplastic control on hippocampal CA1 microcircuits in a cell-specific fashion. Our findings provide new insights on the contribution of interneuron synaptic plasticity in the regulation of the hippocampal network activity and mnemonic processes.

On the use of radon for quantifying the effects of atmospheric stability on urban emissions

Abstract. Radon is increasingly being used as a tool for quantifying stability influences on urban pollutant concentrations. Bulk radon gradients are ideal for this purpose, since the vertical differencing substantially removes contributions from processes on timescales greater than diurnal and (assuming a constant radon source) gradients are directly related to the intensity of nocturnal mixing. More commonly, however, radon measurements are available only at a single height. In this study we argue that single-height radon observations should not be used quantitatively as an indicator of atmospheric stability without prior conditioning of the time series to remove contributions from larger-scale "non-local" processes. We outline a simple technique to obtain an approximation of the diurnal radon gradient signal from a single-height measurement time series, and use it to derive a four category classification scheme for atmospheric stability on a "whole night" basis. A selection of climatological and pollution observations in the Sydney region are then subdivided according to the radon-based scheme on an annual and seasonal basis. We compare the radon-based scheme against a commonly used Pasquill–Gifford (P–G) type stability classification and reveal that the most stable category in the P–G scheme is less selective of the strongly stable nights than the radon-based scheme; this lead to significant underestimation of pollutant concentrations on the most stable nights by the P–G scheme. Lastly, we applied the radon-based classification scheme to mixing height estimates calculated from the diurnal radon accumulation time series, which provided insight to the range of nocturnal mixing depths expected at the site for each of the stability classes.

Conditioned Placebo Analgesia Persists When Subjects Know They Are Receiving a Placebo

Belief in the effectiveness of a placebo treatment is widely thought to be critical for placebo analgesia. Many types of placebo responses—even those that depend on conditioning—appear to be mediated by expectations that are strengthened as treatment cues are reinforced with positive outcomes. However, placebo effects may occur even when participants are aware they are receiving a placebo. To address the question of whether conditioned placebo analgesia can persist in the absence of expectations, we studied the effects of long (4 days) versus short (1 day) conditioning to a placebo treatment. After an initial placebo test, a “reveal” manipulation convincingly demonstrated to participants that they had never received an active drug. Placebo analgesia persisted after the reveal in the long conditioning group only. These findings suggest that reinforcing treatment cues with positive outcomes can create placebo effects that are independent of reported expectations for pain relief. PerspectiveThis article demonstrates a form of placebo analgesia that relies on prior conditioning rather than current expected pain relief. This highlights the importance of prior experience on pain relief and offers insight into the variability of placebo effects across individuals.

Effect of compressibility of synthetic fibers as conditioning materials on dewatering of activated sludge

Efficient solid–liquid phase separation of excess sludge from the mixed-liquor suspended solids in wastewater treatment is difficult to achieve without prior sludge conditioning. Several physical conditioners have been assessed as skeleton builders or filtering aids to reduce sludge compressibility; however, little is known about how the properties of the physical conditioner affect sludge compressibility and dewaterability. In this study, synthetic poly(ethylene terephthalate) (PET), polypropylene, and viscose rayon (VR) fibers were used as physical conditioners for activated sludge, and the effects of the fiber compressibility on the dewaterability of activated sludge collected from a laboratory-scale reactor were assessed. Based on expression experiments using a laboratory-scale apparatus, it was found that: (1) the rate of consolidation of sludge cakes increased after incorporation of synthetic fibers, particularly at the primary stage. (2) The porosity of the sludge cake was maintained only with fibers that required high pressures for compaction (i.e., PET and VR); thus, high dewaterability of the cakes was achieved with these fibers. It is proposed that the compressibility of the physical conditioner may be one of the more important factors for improving sludge dewaterability.

Pharmacogenetic excitation of dorsomedial prefrontal cortex restores fear prediction error.

Pavlovian conditioning involves encoding the predictive relationship between a conditioned stimulus (CS) and an unconditioned stimulus, so that synaptic plasticity and learning is instructed by prediction error. Here we used pharmacogenetic techniques to show a causal relation between activity of rat dorsomedial prefrontal cortex (dmPFC) neurons and fear prediction error. We expressed the excitatory hM3Dq designer receptor exclusively activated by a designer drug (DREADD) in dmPFC and isolated actions of prediction error by using an associative blocking design. Rats were trained to fear the visual CS (CSA) in stage I via pairings with footshock. Then in stage II, rats received compound presentations of visual CSA and auditory CS (CSB) with footshock. This prior fear conditioning of CSA reduced the prediction error during stage II to block fear learning to CSB. The group of rats that received AAV-hSYN-eYFP vector that was treated with clozapine-N-oxide (CNO; 3 mg/kg, i.p.) before stage II showed blocking when tested in the absence of CNO the next day. In contrast, the groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIα-hM3Dq that were treated with CNO before stage II training did not show blocking; learning toward CSB was restored. This restoration of prediction error and fear learning was specific to the injection of CNO because groups that received AAV-hSYN-hM3Dq and AAV-CaMKIIα-hM3Dq that were injected with vehicle before stage II training did show blocking. These effects were not attributable to the DREADD manipulation enhancing learning or arousal, increasing fear memory strength or asymptotic levels of fear learning, or altering fear memory retrieval. Together, these results identify a causal role for dmPFC in a signature of adaptive behavior: using the past to predict future danger and learning from errors in these predictions.

Genome-wide association studies (GWAS) and their importance in asthma

Asthma is a complex disease determined by the interaction of different genes and environmental factors. The first genetic investigations in asthma were candidate gene association studies and linkage studies. In recent years research has focused on association studies that scan the entire genome without any prior conditioning hypothesis: the so-called genome-wide association studies (GWAS). The first GWAS was published in 2007, and described a new locus associated to asthma in chromosome 17q12-q21, involving the ORMDL3, GSDMB and ZPBP2 genes (a description of the genes named in the manuscript are listed in Table 1). None of these genes would have been selected in a classical genetic association study since it was not known they could be implicated in asthma. To date, a number of GWAS studies in asthma have been made, with the identification of about 1000 candidate genes. Coordination of the different research groups in international consortiums and the application of new technologies such as new generation sequencing will help discover new implicated genes and improve our understanding of the molecular mechanisms underlying the disease.

Acute escitalopram but not contextual conditioning exerts a stronger "anxiogenic" effect in rats with high baseline "anxiety" in the acoustic startle paradigm.

Acute administration of selective serotonin reuptake inhibitors (SSRIs) may enhance anxiety in humans, those with anxiety disorders being more susceptible than others. Fear-conditioned or unconditioned acoustic startle and freezing are common measures of fear and/or "anxiety" in rodents that may be used to study this effect of SSRIs preclinically. Our aim was to shed further light on the effect of acute administration of an SSRI, escitalopram (10mg/kg), on startle and freezing in the absence or presence of prior contextual conditioning. Repeated testing also enabled us to evaluate (i) if there are stable inter-animal variations with respect to these parameters in a batch of outbred Wistar rats, (ii) the possible relationship between the two and (iii) if baseline behaviour predicts the response to escitalopram. Inter-animal test-retest correlations were found for both startle and freezing at baseline, and the two parameters also correlated with each other. Both escitalopram and contextual conditioning increased freezing and startle but without exerting any synergistic effect. While animals displaying high startle at baseline showed higher susceptibility to respond to escitalopram, the effect of conditioning was more pronounced in those with low baseline startle. The results support the usefulness of both conditioned and non-conditioned startle and freezing to capture an "anxiogenic" influence of SSRIs. Also, they suggest that baseline non-conditioned startle may predict this response in a manner reflecting the clinical situation in the sense that subjects with high baseline "anxiety" are particularly prone to respond with enhanced "anxiety" following acute SSRI administration.

Relearning a context-shock association after forgetting is an NMDAr-independent process

Infantile amnesia (i.e., the rapid rate of forgetting in young animals) is at least partially due to a memory retrieval, rather than a storage, failure as studies have shown that these engrams can continue to influence later behavior. For example, prior conditioning affects the neural mechanisms underlying future learning. In adult animals, the initial learning of a context-shock association depends upon N-Methyl-D-Aspartate (NMDA) receptors, but this conditioning renders subsequent learning to a similar context NMDAr-independent. In the present study, we examined whether this transition from NMDAr-dependent to NMDAr-independent context conditioning occurs even after infantile amnesia. Experiment 1 demonstrated that infant (i.e., postnatal day 17) rats acquire a context-shock association when trained with multiple shocks, as assessed by context freezing one day later. However, they exhibit significant forgetting of this association 10days later. Experiments 2 and 3 showed that even when animals had forgotten the initial learning experience, future conditioning to the same context was NMDAr-independent. There was evidence of a transition to NMDAr-independent context fear learning in animals exposed only to the foot shock in infancy (Experiment 3) or only to the context in infancy (Experiment 3 but not Experiment 2). These latter results suggest that animals do not have to be exposed to the entire conditioning procedure at postnatal day 17 to show a transition to NMDAr-independent context learning. These experiments add to a growing body of evidence that forgotten infant memories can continue to affect later behavior by demonstrating that prior experience alters the mechanisms of future learning.

Non-invasive urine collection in the female southern hairy-nosed wombat (Lasiorhinus latifrons) with the aid of classical conditioning.

We propose that regular urine samples can be used to monitor and characterize the reproductive cycle of the wombat, but this approach has never before been attempted in a marsupial. We conducted a three stage conditioning process for non-invasive urine collection in captive female wombats, which included (1) initial habituation and observation of urination patterns; (2) classical association of a stimulus with urination and (3) urine collection with the classically-conditioned stimulus. Four of the five female wombats selected for this trial were successfully conditioned for urine collection. During stage 2, the animals urinated in response to tactile stimulation 96 times from 208 attempts (46%). In stage 3, urine was successfully collected 399 times from 485 attempts (82%), with the majority of samples being collected in the morning (280/388). Hand-raised females that were previously conditioned for toileting purposes as pouch young responded more rapidly to the stimulus than juvenile females with no prior conditioning. This study is the first description of a successful method of urine collection by classical conditioning in a marsupial.