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Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17–18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17–18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19–20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body’s physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.
Oxidative stress is implicated in the etiology of schizophrenia, and the antioxidant defense system may be protective in this illness. We examined the major antioxidant glutathione (GSH) in prefrontal brain, and its correlates with clinical and demographic variables, in schizophrenia.
GSH levels were measured in the dorsolateral prefrontal region of 28 patients with chronic schizophrenia using a magnetic resonance spectroscopy sequence specifically adapted for GSH. We examined correlations of GSH levels with age, age at onset of illness, duration of illness, and clinical symptoms.
We found a negative correlation between GSH levels and age at onset (r=-.46, p=.015), and a trend-level positive relationship between GSH and duration of illness (r=.34, p=.076).
Our findings are consistent with a possible compensatory upregulation of the antioxidant defense system with longer duration of illness, and suggests the antioxidant defense system may play a role in schizophrenia.
This is a copy of the slides presented at the meeting but not formally
written up for the volume.
Superparamagnetic iron oxide (SPIO) nanoparticles are prevalent as
nanoprobes for molecular magnetic resonance imaging (MRI), providing
positive or negative contrast by locally affecting the relaxation of
water protons. Fe3O4 nanoparticles are commonly used as a negative MRI
contrast agent, implementing various surface functionalization techniques
to provide molecular targeting to biological macromolecules. The authors
recently demonstrated targeting of cancer antigen 125 (CA125) with
differentiable MRI contrast in human ovarian cancer cell lines using
monoclonal antibodies covalently conjugated to phospholipid micelle
encapsulated 10 nm single crystalline SPIO nanoparticles, demonstrating
molecular targeting capabilities via surface functionalization . While
molecular targeting of SPIO nanoparticles has been thoroughly
demonstrated, the effects of surface modifications have not been studied
in regard to proton relaxation. The authors will present spin-lattice
(T1) and spin-spin (T2) proton relaxometry of SPIO nanoparticles with
varying surface chemistries. The effects of surface modification on T1
and T2 relaxation have not been thoroughly investigated, and results
recently reported by the authors indicate a correlation of spin-spin
relaxation with SPIO nanoparticle hydrodynamic radius . T1 and T2
relaxometry (Varian 300 MHz NMR) of polyethylene glycol modified
(PEGylated) phospholipid micelle encapsulated SPIO nanoparticles and
covalently PEGylated SPIO nanoparticles for varying hydrodynamic radii
will be presented. These results are of particular interest to molecular
imaging applications due to the common practice of SPIO nanoparticle
PEGylation to improve biocompatibility. The authors will also present
results of magnetic anisotropy studies with respect to proton relaxation
by SPIO nanoparticles. Recent work by Roch et al emphasizes the role of
magnetic anisotropy in the proton relaxation mechanism of SPIO
nanoparticles . The authors have synthesized monodisperse Fe3-xCoxO4
nanoparticles with similar properties to SPIO. Cobalt substitution in
SPIO nanoparticles increases the magnetic anisotropy of the SPIO
nanoparticles, thus affecting the proton relaxation. The authors will
present T1 and T2 relaxometry (Varian 300 MHz NMR) of Fe3-xCoxO4
nanoparticles and corresponding SQUID (superconducting quantum
interference device) magnetic anisotropy measurements (Quantum Design,
MPMS-7). The results of this study elucidate the role of magnetic
anisotropy in the proton relaxation mechanism and demonstrates the
feasibility of Fe3-xCoxO4 nanoparticles as a T2 contrast agent.1. Larsen
BA et al, Proceedings of the 5th Annual Meeting of Molecular Imaging,
20062. Barker AJ, Larsen BA et al, Proceedings of the ASME SBC, 20063.
Roch et al, Journal of Mag Res Imaging 14, pp 94-96, 2001.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
This article synthesises the results of a large international study on primary care (PC), the QUALICOPC study.
Since the Alma Ata Declaration, strengthening PC has been high on the policy agenda. PC is associated with positive health outcomes, but it is unclear how care processes and structures relate to patient experiences.
Survey data were collected during 2011–2013 from approximately 7000 PC physicians and 70 000 patients in 34, mainly European, countries. The data on the patients are linked to data on the PC physicians within each country and analysed using multilevel modelling.
Patients had more positive experiences when their PC physician provided a broader range of services. However, a broader range of services is also associated with higher rates of hospitalisations for uncontrolled diabetes, but rates of avoidable diabetes-related hospitalisations were lower in countries where patients had a continuous relationship with PC physicians. Additionally, patients with a long-term relationship with their PC physician were less likely to attend the emergency department. Capitation payment was associated with more positive patient experiences. Mono- and multidisciplinary co-location was related to improved processes in PC, but the experiences of patients visiting multidisciplinary practices were less positive. A stronger national PC structure and higher overall health care expenditures are related to more favourable patient experiences for continuity and comprehensiveness. The study also revealed inequities: patients with a migration background reported less positive experiences. People with lower incomes more often postponed PC visits for financial reasons. Comprehensive and accessible care processes are related to less postponement of care.
The study revealed room for improvement related to patient-reported experiences and highlighted the importance of core PC characteristics including a continuous doctor–patient relationship as well as a broad range of services offered by PC physicians.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
Host-specific interactions can maintain genetic and phenotypic diversity in parasites that attack multiple host species. Host diversity, in turn, may promote parasite diversity by selection for genetic divergence or plastic responses to host type. The parasitic weed purple witchweed [Striga hermonthica (Delile) Benth.] causes devastating crop losses in sub-Saharan Africa and is capable of infesting a wide range of grass hosts. Despite some evidence for host adaptation and host-by-Striga genotype interactions, little is known about intraspecific Striga genomic diversity. Here we present a study of transcriptomic diversity in populations of S. hermonthica growing on different hosts (maize [Zea mays L.] vs. grain sorghum [Sorghum bicolor (L.) Moench]). We examined gene expression variation and differences in allelic frequency in expressed genes of aboveground tissues from populations in western Nigeria parasitizing each host. Despite low levels of host-based genome-wide differentiation, we identified a set of parasite transcripts specifically associated with each host. Parasite genes in several different functional categories implicated as important in host–parasite interactions differed in expression level and allele on different hosts, including genes involved in nutrient transport, defense and pathogenesis, and plant hormone response. Overall, we provide a set of candidate transcripts that demonstrate host-specific interactions in vegetative tissues of the emerged parasite S. hermonthica. Our study shows how signals of host-specific processes can be detected aboveground, expanding the focus of host–parasite interactions beyond the haustorial connection.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
Perceived discrimination (PD) is reliably and strongly associated with partisan identity (PID) among US immigrant minorities such as Latinos and Asian Americans. Yet whether PD causes PID remains unclear, since it is possible that partisanship influences perceptions of discrimination or that other factors drive the observed association. Here, we assess the causal influence of group-level PD on PID using five experiments with Latino and Asian American adults. These experiments varied in important ways: they took place inside and outside the lab, occurred prior to and during Donald Trump’s presidential campaign, and tested different manifestations of PD and partisan attitudes (total n = 2,528). These efforts point to a simple but unexpected conclusion: our experiments and operationalizations do not support the claim that group-targeted PD directly causes PID. These results have important implications for understanding partisanship among immigrants and their co-ethnics and the political incorporation of Latinos and Asian Americans.
The widespread use of herbicides in cropping systems has led to the evolution of resistance in major weeds. The resultant loss of herbicide efficacy is compounded by a lack of new herbicide sites of action, driving demand for alternative weed control technologies. While there are many alternative methods for control, identifying the most appropriate method to pursue for commercial development has been hampered by the inability to compare techniques in a fair and equitable manner. Given that all currently available and alternative weed control methods share an intrinsic energy consumption, the aim of this review was to compare methods based on energy consumption. Energy consumption was compared for chemical, mechanical, and thermal weed control technologies when applied as broadcast (whole-field) and site-specific treatments. Tillage systems, such as flex-tine harrow (4.2 to 5.5 MJ ha−1), sweep cultivator (13 to 14 MJ ha−1), and rotary hoe (12 to 17 MJ ha−1) consumed the least energy of broadcast weed control treatments. Thermal-based approaches, including flaming (1,008 to 4,334 MJ ha−1) and infrared (2,000 to 3,887 MJ ha−1), are more appropriate for use in conservation cropping systems; however, their energy requirements are 100- to 1,000-fold greater than those of tillage treatments. The site-specific application of weed control treatments to control 2-leaf-stage broadleaf weeds at a density of 5 plants m−2 reduced energy consumption of herbicidal, thermal, and mechanical treatments by 97%, 99%, and 97%, respectively. Significantly, this site-specific approach resulted in similar energy requirements for current and alternative technologies (e.g., electrocution [15 to 19 MJ ha−1], laser pyrolysis [15 to 249 MJ ha−1], hoeing [17 MJ ha−1], and herbicides [15 MJ ha−1]). Using similar energy sources, a standardized energy comparison provides an opportunity for estimation of weed control costs, suggesting site-specific weed management is critical in the economically realistic implementation of alternative technologies.
Researchers face a tradeoff when applying latent variable models to time-series, cross-sectional data. Static models minimize bias but assume data are temporally independent, resulting in a loss of efficiency. Dynamic models explicitly model temporal data structures, but smooth estimates of the latent trait across time, resulting in bias when the latent trait changes rapidly. We address this tradeoff by investigating a new approach for modeling and evaluating latent variable estimates: a robust dynamic model. The robust model is capable of minimizing bias and accommodating volatile changes in the latent trait. Simulations demonstrate that the robust model outperforms other models when the underlying latent trait is subject to rapid change, and is equivalent to the dynamic model in the absence of volatility. We reproduce latent estimates from studies of judicial ideology and democracy. For judicial ideology, the robust model uncovers shocks in judicial voting patterns that were not previously identified in the dynamic model. For democracy, the robust model provides more precise estimates of sudden institutional changes such as the imposition of martial law in the Philippines (1972–1981) and the short-lived Saur Revolution in Afghanistan (1978). Overall, the robust model is a useful alternative to the standard dynamic model for modeling latent traits that change rapidly over time.
Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg−1 DEC, 0.15 mg kg−1 ivermectin or 1 mg kg−1 albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.
We evaluated whether a diagnostic stewardship initiative consisting of ASP preauthorization paired with education could reduce false-positive hospital-onset (HO) Clostridioides difficile infection (CDI).
Single center, quasi-experimental study.
Tertiary academic medical center in Chicago, Illinois.
Adult inpatients were included in the intervention if they were admitted between October 1, 2016, and April 30, 2018, and were eligible for C. difficile preauthorization review. Patients admitted to the stem cell transplant (SCT) unit were not included in the intervention and were therefore considered a contemporaneous noninterventional control group.
The intervention consisted of requiring prescriber attestation that diarrhea has met CDI clinical criteria, ASP preauthorization, and verbal clinician feedback. Data were compared 33 months before and 19 months after implementation. Facility-wide HO-CDI incidence rates (IR) per 10,000 patient days (PD) and standardized infection ratios (SIR) were extracted from hospital infection prevention reports.
During the entire 52 month period, the mean facility-wide HO-CDI-IR was 7.8 per 10,000 PD and the SIR was 0.9 overall. The mean ± SD HO-CDI-IR (8.5 ± 2.0 vs 6.5 ± 2.3; P < .001) and SIR (0.97 ± 0.23 vs 0.78 ± 0.26; P = .015) decreased from baseline during the intervention. Segmented regression models identified significant decreases in HO-CDI-IR (Pstep = .06; Ptrend = .008) and SIR (Pstep = .1; Ptrend = .017) trends concurrent with decreases in oral vancomycin (Pstep < .001; Ptrend < .001). HO-CDI-IR within a noninterventional control unit did not change (Pstep = .125; Ptrend = .115).
A multidisciplinary, multifaceted intervention leveraging clinician education and feedback reduced the HO-CDI-IR and the SIR in select populations. Institutions may consider interventions like ours to reduce false-positive C. difficile NAAT tests.
In Scotland, the base of the Ballagan Formation has traditionally been placed at the first grey mudstone within a contiguous Late Devonian to Carboniferous succession. This convention places the Devonian–Carboniferous boundary within the Old Red Sandstone (ORS) Kinnesswood Formation. The consequences of this placement are that tetrapods from the Ballagan Formation were dated as late Tournaisian in age and that the ranges of typically Devonian fish found in the Kinnesswood Formation continued into the Carboniferous. The Pease Bay specimen of the fish Remigolepis is from the Kinnesswood Formation. Comparisons with its range in Greenland, calibrated against spores, show it was Famennian in age. Detailed palynological sampling at Burnmouth from the base of the Ballagan Formation proves that the early Tournaisian spore zones (VI and HD plus Cl 1) are present. The Schopfites species that occurs through most of the succession is Schopfites delicatus rather than Schopfites claviger. The latter species defines the late Tournaisian CM spore zone. The first spore assemblage that has been found in Upper ‘ORS' strata underlying the Ballagan Formation (Preston, Whiteadder Water), contains Retispora lepidophyta and is from the early latest Famennian LL spore zone. The spore samples are interbedded with volcaniclastic debris, which shows that the Kelso Volcanic Formation is, in part, early latest Famennian in age. These findings demonstrate that the Ballagan Formation includes most of the Tournaisian with the Devonian–Carboniferous boundary positioned close to the top of the Kinnesswood Formation. The Stage 6 calcrete at Pease Bay can be correlated to the equivalent section at Carham, showing that it represents a time gap equivalent to the latest Famennian glaciation(s). Importantly, some of the recently described Ballagan Formation tetrapods are older than previously dated and now fill the key early part of Romer's Gap.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
Mismatch negativity (MMN) is an event-related potential (ERP) component reflecting auditory predictive coding. Repeated standard tones evoke increasing positivity (‘repetition positivity’; RP), reflecting strengthening of the standard's memory trace and the prediction it will recur. Likewise, deviant tones preceded by more standard repetitions evoke greater negativity (‘deviant negativity’; DN), reflecting stronger prediction error signaling. These memory trace effects are also evident in MMN difference wave. Here, we assess group differences and test-retest reliability of these indices in schizophrenia patients (SZ) and healthy controls (HC).
Electroencephalography was recorded twice, 2 weeks apart, from 43 SZ and 30 HC, during a roving standard paradigm. We examined ERPs to the third, eighth, and 33rd standards (RP), immediately subsequent deviants (DN), and the corresponding MMN. Memory trace effects were assessed by comparing amplitudes associated with the three standard repetition trains.
Compared with controls, SZ showed reduced MMNs and DNs, but normal RPs. Both groups showed memory trace effects for RP, MMN, and DN, with a trend for attenuated DNs in SZ. Intraclass correlations obtained via this paradigm indicated good-to-moderate reliabilities for overall MMN, DN and RP, but moderate to poor reliabilities for components associated with short, intermediate, and long standard trains, and poor reliability of their memory trace effects.
MMN deficits in SZ reflected attenuated prediction error signaling (DN), with relatively intact predictive code formation (RP) and memory trace effects. This roving standard MMN paradigm requires additional development/validation to obtain suitable levels of reliability for use in clinical trials.