The laminar organization of cell types in macaque cortex and its relationship to neuronal oscillations.

The canonical microcircuit (CMC) has been hypothesized to be the fundamental unit of information processing in cortex. Each CMC unit is thought to be an interconnected column of neurons with specific connections between excitatory and inhibitory neurons across layers. Recently, we identified a conserved spectrolaminar motif of oscillatory activity across the primate cortex that may be the physiological consequence of the CMC. The spectrolaminar motif consists of local field potential (LFP) gamma-band power (40-150 Hz) peaking in superficial layers 2 and 3 and alpha/beta-band power (8-30 Hz) peaking in deep layers 5 and 6. Here, we investigate whether specific conserved cell types may produce the spectrolaminar motif. We collected laminar histological and electrophysiological data in 11 distinct cortical areas spanning the visual hierarchy: V1, V2, V3, V4, TEO, MT, MST, LIP, 8A/FEF, PMD, and LPFC (area 46), and anatomical data in DP and 7A. We stained representative slices for the three main inhibitory subtypes, Parvalbumin (PV), Calbindin (CB), and Calretinin (CR) positive neurons, as well as pyramidal cells marked with Neurogranin (NRGN). We found a conserved laminar structure of PV, CB, CR, and pyramidal cells. We also found a consistent relationship between the laminar distribution of inhibitory subtypes with power in the local field potential. PV interneuron density positively correlated with gamma (40-150 Hz) power. CR and CB density negatively correlated with alpha (8-12 Hz) and beta (13-30 Hz) oscillations. The conserved, layer-specific pattern of inhibition and excitation across layers is therefore likely the anatomical substrate of the spectrolaminar motif. Significance Statement: Neuronal oscillations emerge as an interplay between excitatory and inhibitory neurons and underlie cognitive functions and conscious states. These oscillations have distinct expression patterns across cortical layers. Does cellular anatomy enable these oscillations to emerge in specific cortical layers? We present a comprehensive analysis of the laminar distribution of the three main inhibitory cell types in primate cortex (Parvalbumin, Calbindin, and Calretinin positive) and excitatory pyramidal cells. We found a canonical relationship between the laminar anatomy and electrophysiology in 11 distinct primate areas spanning from primary visual to prefrontal cortex. The laminar anatomy explained the expression patterns of neuronal oscillations in different frequencies. Our work provides insight into the cortex-wide cellular mechanisms that generate neuronal oscillations in primates.

Nanosecond anomaly detection with decision trees and real-time application to exotic Higgs decays.

We present an interpretable implementation of the autoencoding algorithm, used as an anomaly detector, built with a forest of deep decision trees on FPGA, field programmable gate arrays. Scenarios at the Large Hadron Collider at CERN are considered, for which the autoencoder is trained using known physical processes of the Standard Model. The design is then deployed in real-time trigger systems for anomaly detection of unknown physical processes, such as the detection of rare exotic decays of the Higgs boson. The inference is made with a latency value of 30 ns at percent-level resource usage using the Xilinx Virtex UltraScale+ VU9P FPGA. Our method offers anomaly detection at low latency values for edge AI users with resource constraints.

A case series of mucormycosis after covid infection in two hospitals.

This paper aims to discuss clinical aspects of mucormycosis. This case series was conducted in two services, comprising six mucormycosis cases during COVID-19 pandemic. About gender, there are 4 (66.7%) males and 2 (33.3%) females with mean age (48.7 ± 9.4) years. All cases presented complaints of pain and swelling in oral cavity and had an aggressive clinical presentation. Five patients had diabetes and one had a nasal non-Hodgkin lymphoma. Histologically, large, branched, hyphae associated with necrotic areas were observed, confirming microscopically such as mucormycosis through PAS and GMS stains. In four cases, treatment consisted in surgical debridement associated with antifungal therapy. All patients were submitted to debridement and received antifungal treatment (amphotericin B). Five patients were followed up without clinical recurrence, but unfortunately one patient died. Diagnosis of mucormycosis should be early because it is related to high mortality. The treatment consists of surgical debridement associated with antifungal therapy.

Low volumetric bone density is a risk factor for early complications after spine fusion surgery.

This study aims to investigate lumbar spine (LS) volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. INTRODUCTION: Lumbar spine (LS) fusion surgery is increasingly performed worldwide. Complications after fusion result in significant morbidity and healthcare costs. Multiple factors, including osteoporosis, have been suggested to contribute to risk of complications and re-operation. However, most studies have used DXA, which is subject to artifact in patients with spine pathology, and none have investigated the relationship between BMD and timing of post-operative complications. This study aims to investigate LS volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. METHODS: We evaluated a cohort of 359 patients who had initial LS fusion surgery at our institution, had pre-operative LS CTs and post-operative imaging available for review. Demographic factors, smoking status, vBMD, and details of surgical procedure were related to likelihood and timing of post-operative complications. RESULTS: Mean age was 60 ± 14 years, vBMD 122 ± 37 g/cm3. Median follow-up was 11 months. Skeletal complications occurred in 47 patients (13%); 34 patients (10%) required re-operation. Low vBMD (directly measured and estimated using HU) and smoking were associated with increased risk of skeletal complications. Each increase in baseline vBMD of 10 g/cm3 decreased the complication hazard and increased the complication-free duration in time-to-event analysis (hazard ratio 0.91, 95% CI 0.83-0.98, p < 0.02). CONCLUSIONS: Low vBMD was a significant risk factor for early post-operative complications in patients undergoing LS fusion. Prospective studies are needed to confirm these findings and to elucidate the optimal timing for follow-up and strategies for prevention of post-operative complications in this population.

Step-counting accuracy of activity monitors in persons with Down syndrome.

BACKGROUND: Accelerometers and pedometers have been used to monitor the number of steps. However, the evidence on the step-counting accuracy of these devices - especially accelerometers - is limited in persons with Down syndrome (DS). This study therefore examined the accuracy of accelerometers placed on the hip or wrist and of a pedometer with a uni-axial accelerometer mechanism in measuring steps in persons with DS and whether device error is associated with walking speed, height, weight, body mass index, waist circumference, leg length, age or sex. METHOD: Seventeen persons with DS (eight women and nine men; age 33 ± 15 years) walked over-ground for 6 min at their preferred speed. The steps were measured with a hip-worn and a wrist-worn ActiGraph accelerometer using the manufacturer's default (DF) and low-frequency extension (LFE) filters, and with the NL-1000 New Lifestyles pedometer on the hip. Steps were also measured with hand tally which served as the criterion. RESULTS: Absolute percent error was considerable and differed statistically between devices (P = 0.001); however, error improved for accelerometers when LFE was applied (Hip-DF: 31.6 ± 18.8%; Hip-LFE: 9.7 ± 12.8%; Wrist-DF: 32.7 ± 14.2%; Wrist-LFE: 13.6 ± 10.2%; Pedometer: 23.2 ± 22.8%). Bland-Altman plots indicated underestimation of steps for accelerometers and the pedometer. Application of LFE, however, improved the prediction of the accelerometers. The number of steps measured by the hip accelerometer with LFE and by the pedometer did not differ statistically from actual steps. Steps by the remaining methods were significantly lower than hand tally (P ≤ 0.001). Correlations between percent error for each device and walking speed, anthropometry, age or sex ranged between -0.28 and +0.48, and were non-significant, except for age. CONCLUSIONS: The results demonstrated that the pedometer and ActiGraph accelerometers have considerable error in measuring steps of persons with DS. Application of LFE, however, significantly improved the step-counting performance of the Actigraph accelerometers.

Comparison of budburst phenology trends and precision among participants in a citizen science program.

Quantifying shifts in plant phenology in response to climate change represents an ongoing challenge, particularly in mountain ecosystems. Because climate change and phenological responses vary in space and time, we need long-term observations collected at a broad spatial scale. While data collection by volunteers is a promising approach to achieve this goal, one major concern with citizen science programs is the quality and reliability of data. Using a citizen science program (Phenoclim) carried out in the western European Alps, the goals of this study were to analyze (1) factors influencing participant retention rates, (2) the efficacy of a citizen science program for detecting temporal changes in the phenology of mountain trees, (3) differences in budburst date trends among different observer categories, and (4) the precision of trends quantified by different categories of participants. We used 12 years of annual tree phenology measurements recorded by volunteers (schools and private individuals) and professionals within the Phenoclim program. We found decadal-scale shifts in budburst date consistent with the results from other studies, including significant advances in budburst date for the common birch and European ash (- 4.0 and - 6.5 days per decade respectively). In addition, for three of six species, volunteers and professionals detected consistent directional trends. Finally, we show how differences in precision among the categories of participants are determined by the number of years of participation in the program, the number of sites surveyed, and the variability in trends among sites. Overall, our results suggest that participants with a wide range of backgrounds are capable of collecting data that can significantly contribute to the study of the impacts of climate change on mountain plant phenology.

The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

An evaluation of immunization services, using the reaching every district criteria, in two districts of Gujarat, India.

BACKGROUND: Immunizations are considered the most successful and cost-effective public health interventions employed today. While immunization coverage in India has improved dramatically in the last decade, areas of very low coverage persist. The University of Michigan School of Public Health and the Indian Institute of Public Health Gandhinagar collaborated to document strengths and weaknesses of immunization service delivery in two districts in India. METHODS: This report describes a qualitative assessment of clinic level immunization service delivery in ten primary health centers (PHCs) located in two districts of Gujarat, India. Assessment criteria were derived from the Reaching Every District (RED) strategy that is intended to provide a framework for delivering childhood immunizations. Staff from the PHCs were interviewed in April 2013. RESULTS: Interviews revealed several barriers to immunization service delivery including: 1) Vaccine and supply stockouts; 2) Hard to reach communities; 3) Unreliable Internet access; 4) Cold chain equipment malfunctions; 5) Inconsistently maintained and utilized immunization records and registries. CONCLUSIONS: Immunization service delivery is a complex process that can encounter barriers at many stages. A RED-based evaluation of the vaccine delivery system in Gujarat, India identified several points where the system was performing sub-optimally and possible solutions to successfully address these challenges.

Risk factors for measles among infants in Tianjin, China.

OBJECTIVES: Infants aged <8 months are ineligible for measles vaccination in China but represent a disproportionate number of cases. We examined the risk factors for measles among infants in Tianjin, China. STUDY DESIGN: Case-control study. METHODS: Cases were enrolled from a surveillance system, and IgG-negative controls were sampled from registries at immunization clinics. A logistic regression model assessed for risk factors. RESULTS: Among 82 cases and 485 controls, exposure to a municipal hospital (OR [odds ratio]: 5.21; 95% confidence interval [CI]: 1.19-22.82) or a specialty hospital (OR: 13.22; 95% CI: 6.13-28.51) was associated with the disease, whereas visiting a township or district hospitals was not associated with increased odds of measles. CONCLUSIONS: Hospitals were an important focal point of measles transmission for infants. Hospitals, particularly higher-level municipal and specialty hospitals, should enforce infection control programs to separate infants with highly communicable diseases to prevent transmission.

Syndromic surveillance for influenza in Tianjin, China: 2013-14.

Background: Diverse sources of syndromic surveillance including over-the-counter (OTC) drug sales, hospital and school-based influenza-like illness (ILI) and Baidu search queries estimate influenza activity in Tianjin, China. The purpose of this study was to determine which syndromic surveillance systems had the strongest correlation with laboratory-confirmed influenza activity. Methods: Data were obtained from sentinel hospitals and laboratories; sentinel hospitals also reported percentage of ILI. OTC sales and school-based ILI absentee data were provided by public pharmacies and schools. Baidu search queries for influenza surveillance were analyzed. Spearman correlation analysis examined correlations of syndromic systems with laboratory-confirmed data. Results: Syndromic data for hospital ILI%, OTC sales and school-based ILI correlated well with laboratory data (r = 0.732, 0.490 and 0.693, respectively; P < 0.05). Baidu, the predominant Chinese Internet service, searches for 'influenza', 'cough' and 'fever' correlated best with laboratory-confirmed activity; queries for 'fever' were strongest (r = 0.924, P < 0.001). Correlations between school-based ILI and laboratory-confirmed influenza increased from 0.693 to 0.795 after a 1-week lag (P < 0.05). Conclusions: A Baidu query of 'fever' provided the strongest correlation to laboratory surveillance. School-based ILI absence reporting detected influenza virus activity 1 week earlier than laboratory confirmation. Use of diverse syndromic surveillance systems in conjunction with traditional surveillance systems can improve influenza surveillance.

Alisertib demonstrates significant antitumor activity in bevacizumab resistant, patient derived orthotopic models of glioblastoma.

Aurora A kinase (AURKA), a member of the serine/threonine kinase family, plays a critical role in cell division, and it is widely overexpressed in a variety of tumors including glioblastoma (GBM). Alisertib (MLN8237) is an orally administered selective AURKA inhibitor with potent antiproliferative activity, currently undergoing clinical testing in different tumor types. In vitro evaluation of alisertib against the primary GBM lines, GBM6, GBM10, GBM12 and GBM39 showed significant antitumor activity with IC50s ranging between 30 and 95 nM. Orthotopic xenografts of GBM10 and the bevacizumab resistant lines GBM6 and GBM39 were established by implantating 3 × 105 cells in the caudate nucleus of nude mice; animals were randomized to treatment with either alisertib 30 mg/kg/day or vehicle. In all three models, treatment with alisertib resulted in a statistically significant prolongation of survival (p < 0.0001). In addition, alisertib administration in these mice decreased phosphorylated aurora-A, induced mitotic arrest and significantly decreased histone H3 phosphorylation in tumors. In conclusion, alisertib displays significant antitumor activity against primary GBM lines and xenografts, including patient derived GBM lines resistant to bevacizumab; these data support clinical translation in GBM.

Relativistic electrons from sparks in the laboratory.

Discharge experiments were carried out at the Eindhoven University of Technology in 2013. The experimental setup was designed to search for electrons produced in meter-scale sparks using a 1 MV Marx generator. Negative voltage was applied to the high voltage (HV) electrode. Five thin (1 mm) plastic detectors (5 cm2 each) were distributed in various configurations close to the spark gap. Earlier studies have shown (for HV negative) that X-rays are produced when a cloud of streamers is developed 30-60 cm from the negative electrode. This indicates that the electrons producing the X-rays are also accelerated at this location, that could be in the strong electric field from counterstreamers of opposite polarity. Comparing our measurements with modeling results, we find that ∼300 keV electrons produced about 30-60 cm from the negative electrode are the most likely source of our measurements. A statistical analysis of expected detection of photon bursts by these fiber detectors indicates that only 20%-45% of the detected bursts could be from soft (∼10 keV) photons, which further supports that the majority of detected bursts are produced by relativistic electrons.

Foreign body in the appendix presenting as acute appendicitis: a case report.

BACKGROUND: Foreign bodies are a rare cause of appendicitis. In most instances, ingested foreign bodies pass through the alimentary tract asymptomatically. However, those that enter the lumen of the vermiform appendix may not be able to re-enter the colon and may initiate an inflammatory process. We report a case of acute appendicitis induced by an unusual foreign body. CASE PRESENTATION: A 26-year-old Sub-Saharan woman presented with right iliac fossa pain and tenderness. She underwent an open appendectomy which revealed a condom fragment within the appendiceal lumen. A detailed retrospective history confirmed accidental ingestion of the condom 2 weeks prior to onset of symptoms. CONCLUSIONS: Although a rare finding, a variety of foreign bodies can be lodged in the appendix and may instigate an inflammatory process. There is a need to increase awareness of the potential dangers of ingested foreign bodies.

Correlation functions and correlation widths in quantum-chaotic scattering for mesoscopic systems and nuclei.

We derive analytical expressions for the correlation functions of the electronic conductance fluctuations of an open quantum dot under several conditions. Both the variation of energy and that of an external parameter, such as an applied perpendicular or parallel magnetic fields, are considered in the general case of partial openness. These expressions are then used to obtain the ensemble-averaged density of maxima, a measure recently suggested to contain invaluable information concerning the correlation widths of chaotic systems. The correlation width is then calculated for the case of energy variation, and a significant deviation from the Weisskopf estimate is found in the case of two terminals. The results are extended to more than two terminals. All of our results are analytical. The use of these results in other fields, such as nuclei, where the system can only be studied through a variation of the energy, is then discussed.

Clandestine abortion causing uterine perforation and bowel infarction in a rural area: a case report and brief review.

BACKGROUND: An unsafe abortion is defined as a procedure for terminating an unintended pregnancy carried out either by a person lacking the necessary skills or in an environment that does not conform to minimal medical standards or both. Majority of these unsafe abortions are carried out in rural areas of developing countries, usually by unskilled persons who do not have proper knowledge of the anatomy of reproductive organs and in unhygienic environments thus leading to various complications. CASE PRESENTATION: We discuss the case of a 21 year old female who presented in septic shock after she underwent an unsafe abortion of an 11 weeks pregnancy with uterine wall perforation and bowel injury that required resection. CONCLUSION: Unsafe abortion is an important public health problem which accounts for a significant cause of maternal mortality and morbidity in resource poor countries. A high index of suspicion of clandestine abortion with ensuing complications should prevail when faced with a woman of child bearing age with the triad of vaginal bleeding, amenorrhea and pelvic sepsis.

Time domain simulations of preliminary breakdown pulses in natural lightning.

Lightning discharge is a complicated process with relevant physical scales spanning many orders of magnitude. In an effort to understand the electrodynamics of lightning and connect physical properties of the channel to observed behavior, we construct a simulation of charge and current flow on a narrow conducting channel embedded in three-dimensional space with the time domain electric field integral equation, the method of moments, and the thin-wire approximation. The method includes approximate treatment of resistance evolution due to lightning channel heating and the corona sheath of charge surrounding the lightning channel. Focusing our attention on preliminary breakdown in natural lightning by simulating stepwise channel extension with a simplified geometry, our simulation reproduces the broad features observed in data collected with the Huntsville Alabama Marx Meter Array. Some deviations in pulse shape details are evident, suggesting future work focusing on the detailed properties of the stepping mechanism. KEY POINTS: Preliminary breakdown pulses can be reproduced by simulated channel extension Channel heating and corona sheath formation are crucial to proper pulse shape Extension processes and channel orientation significantly affect observations.

Meter-scale spark X-ray spectrum statistics.

X-ray emission by sparks implies bremsstrahlung from a population of energetic electrons, but the details of this process remain a mystery. We present detailed statistical analysis of X-ray spectra detected by multiple detectors during sparks produced by 1 MV negative high-voltage pulses with 1 µs risetime. With over 900 shots, we statistically analyze the signals, assuming that the distribution of spark X-ray fluence behaves as a power law and that the energy spectrum of X-rays detectable after traversing ∼2 m of air and a thin aluminum shield is exponential. We then determine the parameters of those distributions by fitting cumulative distribution functions to the observations. The fit results match the observations very well if the mean of the exponential X-ray energy distribution is 86 ± 7 keV and the spark X-ray fluence power law distribution has index -1.29 ± 0.04 and spans at least 3 orders of magnitude in fluence.

High-throughput small molecule screening reveals structurally diverse compounds that inhibit the growth of Escherichia coli O157:H7 in vitro.

Escherichia coli O157:H7 colonizes the gastrointestinal tract of ruminants asymptomatically and may enter the human food supply through fecal contamination. A fraction of individuals infected by E. coli O157:H7 develop hemolytic uremic syndrome, a life-threatening condition. When individuals infected by E. coli O157:H7 are treated with certain antibiotics, an increased incidence of hemolytic uremic syndrome may result. This finding supports the need to identify novel compounds that can either reduce the load of E. coli O157:H7 entering the human food supply or serve as alternative therapeutic treatments for infected individuals. We developed a high-throughput turbidometric assay to identify novel compounds that inhibit E. coli O157:H7 growth. Pin transfers were performed to introduce small molecule libraries into 384-well plates, where each well contained approximately 5.0 log CFU of E. coli O157:H7. Plates were incubated at 37°C for 18 h, and the optical density was measured to determine the effect of each small molecule. A total of 64,562 compounds were screened in duplicate, and 43 unique compounds inhibited E. coli O157:H7 growth. Thirty-eight of the 43 inhibitory compounds belonged to known bioactive libraries, and the other 5 compounds were from commercial libraries derived from splitting and pooling. Inhibitory compounds from known bioactive libraries were most frequently therapeutic antibiotics (n = 34) but also included an antiviral compound, a compound that disrupts the citric acid cycle, and two biguanide compounds, which have been used for various nonclinical applications. We identified two novel compounds (i.e., biguanides) that should be studied further for their ability to reduce pathogen populations in foods.

Naturally colonized beef cattle populations fed combinations of yeast culture and an ionophore in finishing diets containing dried distiller's grains with solubles had similar fecal shedding of Escherichia coli O157:H7.

Beef steers (n = 252) were used to evaluate the effects of dietary supplement on fecal shedding of Escherichia coli O157:H7. Seven pens of 9 steers (63 steers per treatment) were fed diets supplemented with or without yeast culture (YC) or monensin (MON) and their combination (YC × MON). YC and MON were offered at 2.8 g/kg and 33 mg/kg of dry matter intake, respectively. Environmental sponge samples (from each pen floor, feed bunk, and water trough) were collected on day 0. Rectal fecal grab samples were collected on days 0, 28, 56, 84, 110, and 125. Samples were collected and pooled by pen and analyzed for presumptive E. coli O157:H7 colonies, which were confirmed by a multiplex PCR assay and characterized by pulsed-field gel electrophoresis (PFGE) typing. On day 0, E. coli O157:H7 was detected in 7.0% of feed bunk samples and 14.3% of pen floor samples but in none of the water trough samples. The 71.4% prevalence of E. coli O157:H7 in fecal samples on day 0 decreased significantly (P < 0.05) over time. E. coli O157:H7 fecal shedding was not associated with dietary treatment (P > 0.05); however, in cattle fed YC and YC × MON fecal shedding was 0% by day 28. Eight Xba I PFGE subtypes were identified, and a predominant subtype and three closely related subtypes (differing by three or fewer bands) accounted for 78.7% of environmental and fecal isolates characterized. Results from this study indicate that feeding YC to cattle may numerically decrease but not eliminate fecal shedding of E. coli O157:H7 at the onset of treatment and that certain E. coli O157 subtypes found in the feedlot environment may persist in feedlot cattle.

Analysis of suicidality in pooled data from 2 double-blind, placebo-controlled aripiprazole adjunctive therapy trials in major depressive disorder.

OBJECTIVE: To assess the impact of adjunctive aripiprazole versus adjunctive placebo treatment on suicidality in patients with major depressive disorder. METHOD: Data were pooled from 2 identical aripiprazole augmentation studies. Patients with DSM-IV-TR-diagnosed major depressive disorder with an inadequate response to 8 weeks of prospective antidepressant treatment were randomly assigned to adjunctive placebo or adjunctive aripiprazole (2-20 mg/d) treatment for 6 weeks. Adverse events related to suicidality were identified in the adverse event database using the Medical Dictionary for Regulatory Activities-preferred term. Treatment-emergent suicidal ideation was defined using item 10 (suicidality) of the Montgomery-Åsberg Depression Rating Scale (MADRS) and item 18 (suicidality) of the Inventory of Depressive Symptomatology (IDS). RESULTS: In total, 737 patients were included in the safety database (aripiprazole n = 371; placebo n = 366). No suicides were reported. There were no treatment-emergent, suicide-related adverse events in the aripiprazole group; 2 patients in the placebo group had ≥ 1 adverse event related to suicide (both suicidal ideation). More placebo than aripiprazole patients > 25 years old experienced a 2-point (P < .01) or 1-point (P < .05) worsening of MADRS item 10 scores. For this age group, 2-point improvement in MADRS item 10 scores and 1-point improvement of IDS item 18 scores were significantly more common in aripiprazole patients than placebo patients (both P < .05). CONCLUSIONS: This post hoc analysis demonstrated that adjunctive aripiprazole treatment in patients with depression with a history of an inadequate response to antidepressant medication is associated with a decreased rate of suicidality in a group of subjects not at significant risk. Prospective trials directly assessing suicidality are needed to further understand the benefits of an adjunctive antipsychotic in an at-risk population. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.