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Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.
Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).
We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = −0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = −0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = −0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = −0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.
Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.
Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.
A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.
Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.
To evaluate whether incorporating mandatory prior authorization for Clostridioides difficile testing into antimicrobial stewardship pharmacist workflow could reduce testing in patients with alternative etiologies for diarrhea.
Single center, quasi-experimental before-and-after study.
Tertiary-care, academic medical center in Ann Arbor, Michigan.
Adult and pediatric patients admitted between September 11, 2019 and December 10, 2019 were included if they had an order placed for 1 of the following: (1) C. difficile enzyme immunoassay (EIA) in patients hospitalized >72 hours and received laxatives, oral contrast, or initiated tube feeds within the prior 48 hours, (2) repeat molecular multiplex gastrointestinal pathogen panel (GIPAN) testing, or (3) GIPAN testing in patients hospitalized >72 hours.
A best-practice alert prompting prior authorization by the antimicrobial stewardship program (ASP) for EIA or GIPAN testing was implemented. Approval required the provider to page the ASP pharmacist and discuss rationale for testing. The provider could not proceed with the order if ASP approval was not obtained.
An average of 2.5 requests per day were received over the 3-month intervention period. The weekly rate of EIA and GIPAN orders per 1,000 patient days decreased significantly from 6.05 ± 0.94 to 4.87 ± 0.78 (IRR, 0.72; 95% CI, 0.56–0.93; P = .010) and from 1.72 ± 0.37 to 0.89 ± 0.29 (IRR, 0.53; 95% CI, 0.37–0.77; P = .001), respectively.
We identified an efficient, effective C. difficile and GIPAN diagnostic stewardship approval model.
Raw milk cheeses are commonly consumed in France and are also a common source of foodborne outbreaks (FBOs). Both an FBO surveillance system and a laboratory-based surveillance system aim to detect Salmonella outbreaks. In early August 2018, five familial FBOs due to Salmonella spp. were reported to a regional health authority. Investigation identified common exposure to a raw goats' milk cheese, from which Salmonella spp. were also isolated, leading to an international product recall. Three weeks later, on 22 August, a national increase in Salmonella Newport ST118 was detected through laboratory surveillance. Concomitantly isolates from the earlier familial clusters were confirmed as S. Newport ST118. Interviews with a selection of the laboratory-identified cases revealed exposure to the same cheese, including exposure to batches not included in the previous recall, leading to an expansion of the recall. The outbreak affected 153 cases, including six cases in Scotland. S. Newport was detected in the cheese and in the milk of one of the producer's goats. The difference in the two alerts generated by this outbreak highlight the timeliness of the FBO system and the precision of the laboratory-based surveillance system. It is also a reminder of the risks associated with raw milk cheeses.
We aimed to assess the incidence of obstructive sleep apnoea (OSA) in people with schizophrenia, to explore clinical associates with OSA and how well OSA screening tools perform in this population.
All patients registered in a community outpatient Clozapine clinic, between January 2014 and March 2016, were consecutively approached to participate. Participants were screened for OSA using at home multichannel polysomnography (PSG) and were diagnosed with OSA if the apnoea-hypopnoea index (AHI) was >10 events/hr. Univariate comparison of participants to determine whether AHI > 10 events/hr was associated with demographic factors, anthropometric measures and psychiatric symptoms and cognition was performed. The sensitivity, specificity, positive predictive value and negative predictive value of the commonly used sleep symptoms scales and OSA screening tools were also determined.
Thirty participants were recruited, 24 men and 6 women. Mean age was 38.8 (range: 25–60), and mean body mass index (BMI) was 35.7 (range 19.9–62.1). The proportion of participants with OSA (AHI > 10 events/hr) was 40%, 18 (60%) had no OSA, 4 (13%) had mild OSA (AHI 10.1–20), zero participants had moderate OSA (AHI 20.1–30) and 8 (27%) had severe OSA (AHI > 30). Diagnosis of OSA was significantly associated with increased weight, BMI, neck circumference and systolic blood pressure. Diagnosis of OSA was not significantly associated with Positive and Negative Symptoms Scale, Montgomery Asperger’s Depression Rating Scale, Personal and Social Performance scale or Brief Assessment of Cognition for Schizophrenia scores. All OSA screening tools demonstrated poor sensitivity and specificity for a diagnosis of OSA.
OSA was highly prevalent in this cohort of people with schizophrenia and was associated with traditional anthropometric OSA risk factors.
Brain alterations have been sought since the beginning of the century to explain the ‘dementia’ of dementia præcox. Kraepelin suggested in 1913 that it might have its internal origins in early childhood, while Southard (1915) considered likely a congenital or early acquired basis for the development of the disease. Afterwards, degenerative processes were described for decades until neurodevelopmental theories emerged recently (Lewis, 1988).
Using pneumoencephalography, Jacobi and Winkler (1927) first reported that some patients with schizophrenia presented enlarged ventricles. Johnstone et al (1976, 1978), in CT-scan studies, observed an increase in mean lateral ventricular size in a group of institutionalized schizophrenic patients. This finding has been replicated by other studies (Weinberger et al, 1983) but challenged by others (Gluck et al, 1980; Jernigan et al, 1982).
The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.
Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.
The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.
The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
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.
OBJECTIVES/SPECIFIC AIMS: The purpose of the present secondary data analysis was to examine the effect of moderate-severe disturbed sleep before the start of radiation therapy (RT) on subsequent RT-induced pain. METHODS/STUDY POPULATION: Analyses were performed on 676 RT-naïve breast cancer patients (mean age 58, 100% female) scheduled to receive RT from a previously completed nationwide, multicenter, phase II randomized controlled trial examining the efficacy of oral curcumin on radiation dermatitis severity. The trial was conducted at 21 community oncology practices throughout the US affiliated with the University of Rochester Cancer Center NCI’s Community Oncology Research Program (URCC NCORP) Research Base. Sleep disturbance was assessed using a single item question from the modified MD Anderson Symptom Inventory (SI) on a 0–10 scale, with higher scores indicating greater sleep disturbance. Total subjective pain as well as the subdomains of pain (sensory, affective, and perceived) were assessed by the short-form McGill Pain Questionnaire. Pain at treatment site (pain-Tx) was also assessed using a single item question from the SI. These assessments were included for pre-RT (baseline) and post-RT. For the present analyses, patients were dichotomized into 2 groups: those who had moderate-severe disturbed sleep at baseline (score≥4 on the SI; n=101) Versus those who had mild or no disturbed sleep (control group; score=0–3 on the SI; n=575). RESULTS/ANTICIPATED RESULTS: Prior to the start of RT, breast cancer patients with moderate-severe disturbed sleep at baseline were younger, less likely to have had lumpectomy or partial mastectomy while more likely to have had total mastectomy and chemotherapy, more likely to be on sleep, anti-anxiety/depression, and prescription pain medications, and more likely to suffer from depression or anxiety disorder than the control group (all p’s≤0.02). Spearman rank correlations showed that changes in sleep disturbance from baseline to post-RT were significantly correlated with concurrent changes in total pain (r=0.38; p<0.001), sensory pain (r=0.35; p<0.001), affective pain (r=0.21; p<0.001), perceived pain intensity (r=0.37; p<0.001), and pain-Tx (r=0.35; p<0.001). In total, 92% of patients with moderate-severe disturbed sleep at baseline reported post-RT total pain compared with 79% of patients in the control group (p=0.006). Generalized linear estimating equations, after controlling for baseline pain and other covariates (baseline fatigue and distress, age, sleep medications, anti-anxiety/depression medications, prescription pain medications, and depression or anxiety disorder), showed that patients with moderate-severe disturbed sleep at baseline had significantly higher mean values of post-RT total pain (by 39%; p=0.033), post-RT sensory pain (by 41%; p=0.046), and post-RT affective pain (by 55%; p=0.035) than the control group. Perceived pain intensity (p=0.066) and pain-Tx (p=0.086) at post-RT were not significantly different between the 2 groups. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings suggest that moderate-severe disturbed sleep prior to RT is an important predictor for worsening of pain at post-RT in breast cancer patients. There could be several plausible reasons for this. Sleep disturbance, such as sleep loss and sleep continuity disturbance, could result in impaired sleep related recovery and repair of tissue damage associated with cancer and its treatment; thus, resulting in the amplification of pain. Sleep disturbance may also reduce pain tolerance threshold through increased sensitization of the central nervous system. In addition, pain and sleep disturbance may share common neuroimmunological pathways. Sleep disturbance may modulate inflammation, which in turn may contribute to increased pain. Further research is needed to confirm these findings and whether interventions targeting sleep disturbance in early phase could be potential alternate approaches to reduce pain after RT.
OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.
This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (−165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (−270 g/day). Low responses were observed on growth rate (−12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; −2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (−0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (−10% after five generations of selection) and activity (−21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.
The majority of improvements to LIB technology have come through the development of new novel cathode materials. One promising cathode material is Li2FeSiO4 (LFS), desirable for its low cost and high theoretical capacity. However, the ionic conduction and transport mechanisms within this material are still not well understood, and require further investigation to improve upon cycling rate performance. To this end combined measurements of XRD & XANES have been performed in operando on LFS during electrochemical cycling, i.e. at selected electrochemical states of charge during the formation cycle the crystalline structure and the transition metal oxidation state as well as the site symmetry were characterized via the two aforementioned techniques. These in operando measurements expose once more a charging rate-dependent phase evolution during the formation cycle, which can be well characterized using a simplified equivalent circuit analogue.
This book addresses the question of whether there are continuities in Latin spanning the period from the early Republic through to the Romance languages. It is often maintained that various usages admitted by early comedy were rejected later by the literary language but continued in speech, to resurface centuries later in the written record (and in Romance). Are certain similarities between early and late Latin all that they seem, or might they be superficial, reflecting different phenomena at different periods? Most of the chapters, on numerous syntactic and other topics and using different methodologies, have a long chronological range. All attempt to identify patterns of change that might undermine any theory of submerged continuity. The patterns found are summarised in a concluding chapter. The volume addresses classicists with an interest in any of the different periods of Latin, and Romance linguists.