Differentiating responders and non-responders to rTMS treatment for depression after one week using resting EEG connectivity measures.

BACKGROUND: Non-response to repetitive transcranial magnetic stimulation (rTMS) treatment for depression is costly for both patients and clinics. Simple and cheap methods to predict response would reduce this burden. Resting EEG measures differentiate responders from non-responders, so may have utility for response prediction. METHODS: Fifty patients with treatment resistant depression and 21 controls had resting electroencephalography (EEG) recorded at baseline (BL). Patients underwent 5-8 weeks of rTMS treatment, with EEG recordings repeated at week 1 (W1). Forty-two participants had valid BL and W1 EEG data, and 12 were responders. Responders and non-responders were compared at BL and W1 in measures of theta (4-8 Hz) and alpha (8-13 Hz) power and connectivity, frontal theta cordance and alpha peak frequency. Control group comparisons were made for measures that differed between responders and non-responders. A machine learning algorithm assessed the potential to differentiate responders from non-responders using EEG measures in combination with change in depression scores from BL to W1. RESULTS: Responders showed elevated theta connectivity across BL and W1. No other EEG measures differed between groups. Responders could be distinguished from non-responders with a mean sensitivity of 0.84 (p = 0.001) and specificity of 0.89 (p = 0.002) using cross-validated machine learning classification on the combination of all EEG and mood measures. LIMITATIONS: The low response rate limited our sample size to only 12 responders. CONCLUSION: Resting theta connectivity at BL and W1 differ between responders and non-responders, and show potential for predicting response to rTMS treatment for depression.

Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction. PRIMARY HYPOTHESES: We expected higher theta and alpha activity in responders compared to non-responders to rTMS. METHODS: Fifty patients with treatment resistant depression and twenty controls performed a WM task while electroencephalography (EEG) was recorded. Patients underwent 5-8 weeks of rTMS treatment, repeating the EEG at week 1 (W1). Of the 39 participants with valid WM-related EEG data from baseline and W1, 10 were responders. Comparisons between responders and non-responders were made at baseline and W1 for measures of theta (4-8 Hz), upper alpha (10-12.5 Hz), and gamma (30-45 Hz) power, connectivity, and theta-gamma coupling. The control group's measures were compared to the depression group's baseline measures separately. RESULTS: Responders showed higher levels of WM-related fronto-midline theta power and theta connectivity compared to non-responders at baseline and W1. Responder's fronto-midline theta power and connectivity was similar to controls. Responders also showed an increase in gamma connectivity from baseline to W1, with a concurrent improvement in mood and WM reaction times. An unbiased combination of all measures provided mean sensitivity of 0.90 at predicting responders and specificity of 0.92 in a predictive machine learning algorithm. CONCLUSION: Baseline and W1 fronto-midline theta power and theta connectivity show good potential for predicting response to rTMS treatment for depression.

Re-aerosolization of Bacillus thuringiensis spores from concrete and turf.

Spores of Bacillus anthracis deposited on surfaces can become airborne again as a result of air currents and mechanical forces. As such, they are a potential source of infection by inhalation. Spores of Bacillus thuringiensis were used to quantify this phenomenon in a simulation of outdoor conditions. Concrete and turf surfaces were inoculated by aerosol to produce high spore densities (greater than 1 × 109  CFU per m2 ) which were then subjected to the passage of air at 10 ms-1 with and without simulated walking. Re-aerosolized spores were sampled by wetted wall cyclone air samplers. The mean total re-aerosolization rate from concrete (m-2  min-1 ) was 1·16 × 10-3 for wind alone and 3·2 × 10-3 for wind and simulated walking while for turf the respective values were 2·7 × 10-4 and 6·7 × 10-4 . SIGNIFICANCE AND IMPACT OF THE STUDY: Following the malicious and/or accidental release of an aerosol of Bacillus anthracis spores, the immediate risk of human inhalation would decrease as the spores were deposited on surfaces or diluted by wind flow. There is, however, a concern that the deposited spores could become re-aerosolized and so present an ongoing hazard. Using an accurate simulant for B. anthracis spores a method is reported here that allowed the enumeration of re-aerosolized spores from concrete and turf by wind flow and footfall. Under the conditions used, the rates of re-aerosolization were low. These findings will need to be verified under real outdoor conditions before the true significance in terms of secondary exposure to pathogenic spores can be assessed.

Patient characteristics, interventions and outcomes of 1151 rapid response team activations in a tertiary hospital: a prospective study.

BACKGROUND: The characteristics of mature contemporary rapid response systems are unclear. AIM: To determine the patient characteristics, processes and outcomes, both in-hospital and post-discharge, of a well-established rapid response system in a tertiary adult hospital. METHODS: This is a prospective study of consecutive rapid response team (RRT) activations between 1 July and 25 November 2015. Variables included patient characteristics, timing, location and triggers of RRT activations, interventions undertaken, mortality and readmission status at 28 days post-discharge. RESULTS: A total of 1151 RRT activations was analysed (69.1 per 1000 admissions), involving 800 patients, of whom 81.5% were emergency admissions. A total of 351 (30.5%) activations comprised repeat activations for the same patient. Most activations (723; 62.8%) occurred out of hours, and 495 (43%) occurred within 48 h of admission. Hypotension, decreased level of consciousness and oxygen desaturation were the most common triggers. Advanced life support was undertaken in less than 7%; 198 (17.2%) responses led to transfer to higher-level care units. Acute resuscitation plans were noted for only 29.1% of RRT activations, with 80.3% stipulating supportive care only. A total of 103 (12.6%) patients died in hospital, equalling 14 deaths per 100 RRT activations. At 28 days, 150 (18.8%) patients had died, significantly more among those with multiple versus single RRT activations (24.9 vs 16.6%; odds ratio 1.66, 95% confidence interval 1.31-2.44; P = 0.013). CONCLUSION: Relatively few RRT activations are associated with acute resuscitation plans, and most interventions during RRT responses are low level. The high rate of post-RRT deaths and transfers to higher-level care units calls for the prospective identification of such patients in targeting appropriate care.

Ligand-Specific Transcriptional Mechanisms Underlie Aryl Hydrocarbon Receptor-Mediated Developmental Toxicity of Oxygenated PAHs.

Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds.

Rapid response teams in adult hospitals: time for another look?

Rapid response teams (RRT), alternatively termed medical emergency teams, have become part of the clinical landscape in the majority of adult hospitals throughout Australia and New Zealand. These teams aim to bring critical care expertise to the bedside of clinically deteriorating patients residing in general hospital wards with the aim of preventing adverse outcomes, in particular death or cardiorespiratory arrests. While the concept of RRT has considerable face validity, there is little high quality evidence of their effectiveness and much uncertainty as to the optimal methods for identifying patients in need of RRT and calling the RRT (afferent limb) and how, and with whom, the RRT should then respond (efferent limb). Adverse unintended consequences of RRT systems and the opportunity costs involved in maintaining such systems have not been subject to study, amid concerns RRT may be compensating for other potentially remediable system of care failures. This article presents an overview of the current state of play of RRT in hospital practice as they pertain to the care of adult patients and identifies several issues around their implementation and evaluation that should be subject to further research.

NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy.

The BUN and FASTER studies, two prospective multicenter trials in the United States, validated the accuracy and detection rates of first and second trimester screening previously reported abroad. These studies, coupled with the 2007 release of the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin that endorsed first trimester screening as an alternative to traditional second trimester multiple marker screening, led to an explosion of screening options available to pregnant women. ACOG also recommended that invasive diagnostic testing for chromosome aneuploidy be made available to all women regardless of maternal age. More recently, another option known as Non-invasive Prenatal Testing (NIPT) became available to screen for chromosome aneuploidy. While screening and testing options may be limited due to a variety of factors, healthcare providers need to be aware of the options in their area in order to provide their patients with accurate and reliable information. If not presented clearly, patients may feel overwhelmed at the number of choices available. The following guideline includes recommendations for healthcare providers regarding which screening or diagnostic test should be offered based on availability, insurance coverage, and timing of a patient's entry into prenatal care, as well as a triage assessment so that a general process can be adapted to unique situations.

Investigations into the source of two fungicides measured in the air for 24 hours following application to a cereal crop.

Airborne pesticides can be detected near to recently-treated arable fields for a period of days following the application. Identifying the source of such pesticides is important in developing predictive models for use in exposure and risk assessments. Previous work showed levels of pesticide in the air that were higher than expected for a low-vapour-pressure active ingredient, epoxiconazole, and comparable with an active ingredient of a significantly higher vapour pressure, fenpropidin. It was possible that the measured concentrations could be attributed to 'dust' particles emitted from the crop, either biological material contaminated with pesticide or solid dried deposits of active ingredient and other formulation components. A second experiment was therefore undertaken to measure airborne concentrations of the same active ingredients and to determine whether some or all of the measured airborne pesticide could be attributed to particles, using a Marple personal cascade impactor, which collects particles in the range 0.3 - 50 microm. Such samplers are not optimised to give good sampling efficiencies under the proposed field conditions, so some initial tests were undertaken in the Silsoe wind tunnel to assess its ability to sample particles in an air flow. In the subsequent field trial, a 192 m square plot in a commercially established winter cereal crop was sprayed with a tank mix of commercial formulations of epoxiconazole and fenpropidin. Measurements of airborne pesticides were made for 24 hours following the application with suction samplers attached to tenax tubes to evaluate vapour concentrations and with the cascade impactor to determine whether contaminated airborne particles were present. The concentrations of pesticide measured with the tenax tubes were significantly higher than the particulate component detected on the cascade impactor plates and it is therefore it was very unlikely that there was a significant contribution from pesticide-laden particles to the airborne concentration. Although it is clear that under these particular experimental conditions, airborne contaminated particles were not detected in significant quantities after the application, it is possible that this could occur under different circumstances, such as during pollen release or harvest.

The DIURNAL project: DIURNAL and circadian expression profiling, model-based pattern matching, and promoter analysis.

The DIURNAL project ( http://diurnal.cgrb.oregonstate.edu/ ) provides a graphical interface for mining and viewing diurnal and circadian microarray data for Arabidopsis thaliana, poplar, and rice. The database is searchable and provides access to several user-friendly Web-based data-mining tools with easy-to-understand output. The associated tools include HAYSTACK ( http://haystack.cgrb.oregonstate.edu/ ) and ELEMENT ( http://element.cgrb.oregonstate.edu/ ). HAYSTACK is a model-based pattern-matching algorithm for identifying genes that are coexpressed and potentially coregulated. HAYSTACK can be used to analyze virtually any large-scale microarray data set and provides an alternative method for clustering microarray data from any experimental system by grouping together genes whose expression patterns match the same or similar user-defined patterns. ELEMENT is a Web-based program for identifying potential cis-regulatory elements in the promoters of coregulated genes in Arabidopsis, poplar, and rice. Together, DIURNAL, HAYSTACK, and ELEMENT can be used to facilitate cross-species comparisons among the plant species supported and to accelerate functional genomics efforts in the laboratory.

Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families.

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.

Regulation of the strypsin-related proteinase ISP2 by progesterone in endometrial gland epithelium during implantation in mice.

Hormones prepare the uterus for the arrival and subsequent invasion of the embryo during pregnancy. Extracellular matrix-degrading proteinases and their inhibitors are involved in this integration process. Recent genetic evidence indicates that there is redundancy within the implantation proteinase cascade, indicating that additional proteinases may be involved. Recently, we described a novel implantation serine proteinase (ISP1) gene that encodes the embryo-derived enzyme strypsin, which is necessary for blastocyst hatching in vitro and the initiation of invasion. The evidence presented in the present study indicates that a second proteinase secreted from the uterus also participates in lysis of the zona pellucida. A second implantation serine proteinase gene (ISP2) was isolated, which encodes a related secreted tryptase expressed specifically within uterine endometrial glands. In pseudopregnancy, ISP2 gene expression is dependent on progesterone priming and is inhibited by the antiprogestin RU486. On the basis of similarities between ISP2 gene expression and that of a progesterone-regulated luminal proteinase associated with lysis of the zona pellucida, it is possible that the strypsin-related protein, ISP2, may encode a zona lysin proteinase.

A novel murine tryptase involved in blastocyst hatching and outgrowth.

Before implantation the blastocyst is maintained within a proteinaceous coat, the zona pellucida, which prevents polyspermy and ectopic pregnancy. An extracellular trypsin-like activity, which is necessary for hatching from the zona pellucida in vitro, is localized to the abembryonic pole of the blastocyst. Upon hatching, the extracellular matrix-degrading proteinases urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) are thought to promote blastocyst invasion. However, gene disruption experiments have demonstrated that uPA and MMP-9 are dispensable and, thus, that other key enzymes are involved in implantation. In this study, a novel implantation serine proteinase (ISP1) gene, which is distantly related to haematopoietic tryptases and represents a novel branch of the S1 proteinase family, was cloned. ISP1 is expressed throughout morulae and blastocysts during hatching and outgrowth. Abrogation of ISP1 mRNA accumulation using antisense oligodeoxynucleotides disrupts blastocyst hatching and outgrowth in vitro. The results of this study indicate that the ISP1 gene probably encodes the long sought after 'hatching enzyme' that is localized to the abembryonic pole during hatching in vitro. ISP1 is the earliest embryo-specific proteinase to be expressed in implantation and may play a critical role in connecting embryo hatching to the establishment of implantation competence at the abembryonic pole of the blastocyst.

Accidental and nonaccidental femur fractures in children.

A retrospective review of 207 patients younger than 6 years of age who sustained nonpathologic diaphyseal femur fractures was done, which emphasized the characteristics of accidental versus nonaccidental injury. There were 214 fractures in 123 boys and 83 girls (the gender of one patient was unknown). The average age of the patients was 2.73 years. Mechanisms of injury were pedestrian struck by a car (62 patients), falls (92 patients), and motor vehicle accidents (10 patients). Nineteen patients did not have a history of trauma. Seventy-six cases were investigated for child abuse. The results of 13 investigations were positive. Overall, the morphologic features of the fractures were transverse (38%), spiral (27%), and oblique (17%). In the investigated group, 27% of the fractures were transverse, 39% were spiral, and 15% were oblique. In those cases with positive results of the investigation, 36% of the fractures were transverse, 36% were spiral, and 7% were oblique. Although transverse fractures are most common in accidental and nonaccidental injuries, many practitioners think spiral fractures are pathognomonic of abuse. The current data show that although spiral fractures were less common than transverse fractures overall, and no more common in the cohort of patients in whom the results of the child abuse investigations were positive, they were overrepresented in the cohort that was investigated. This suggests that spiral fractures are viewed as particularly suspicious, which may lead to missed cases of nonaccidental injury in children with transverse fractures.

Into the mix results from PPS per-episode demonstration & case-mix study.

The Health Care Financing Administration (HCFA) released two reports in October 1999 that provide insight into the development of a per-episode prospective payment system (PPS) for Medicare home health. These reports provide important clues about two critical issues: the impact of per-episode payment on the cost of providing home health care, and how to predict the resources used by home health patients.

Complications of osteotomies in severe cerebral palsy.

Seventy-nine consecutive children with cerebral palsy who underwent osteotomies about the hip for subluxation or dislocation were studied retrospectively to determine risk factors that would correlate with postoperative complications of death, fracture, or decubitus ulcer. Except for the three patients who died, all of the children had > or = 1 year of follow-up. Twenty (25%) patients had at least one complication. Three children died; one at 1 week, one at 2 weeks, and one at 5 months after surgery. Sixteen patients sustained 25 fractures. All were managed with cast or splint immobilization in the clinic. Five patients developed decubitus ulcers requiring > or = 2 weeks of local care, but none required skin grafts or flaps. Complications occurred in 13 (68%) of 19 children with gastrostomies or tracheostomies but in only seven (12%) of the remaining 60 children. Only one (8%) of 13 ambulatory patients had a complication compared with 19 (29%) of 66 nonambulatory patients. In conclusion, ambulatory function correlates well with the risk of complications after osteotomies. A nonambulatory patient with a gastrostomy or tracheostomy is at even greater risk. Fortunately the fractures and ulcers observed in this series healed uneventfully with no operative intervention.

Reducing violence using community-based advocacy for women with abusive partners.

An intensive community-based advocacy intervention was designed and evaluated by randomly assigning 278 battered women to an experimental or control condition. Participants were interviewed 6 times over a period of 2 years. Retention rate averaged 95% over the 2 years. The 10-week postshelter intervention involved providing trained advocates to work 1-on-1 with women, helping generate and access the community resources they needed to reduce their risk of future violence from their abusive partners. Women who worked with advocates experienced less violence over time, reported higher quality of life and social support, and had less difficulty obtaining community resources. More than twice as many women receiving advocacy services experienced no violence across the 2 years postintervention compared with women who did not receive such services.

"Why don't they just call the cops?": Reasons for differential police contact among women with abusive partners.

Incidents of domestic violence are frequently not reported to police (e.g., Johnson, 1990; Langan & Innes, 1986; Roy, 1977), and people commonly assume that women's reasons for not calling about violence by a current or former partner are intrapersonal (e.g., shame, embarrassment, love). However, few researchers have asked battered women themselves about the frequency of their police contacts and their reasons for not calling the police. In this study, participants were recruited from a battered women's shelter and asked about their experiences with the police over the prior 6 months. Two thirds of the sample had had contact with the police during that time, but most did not have as much contact with the police as they had needed. Women gave multiple reasons for not calling the police; these reasons frequently included situational barriers, such as being physically prevented from using the telephone and/or being threatened with more violence. Only 3% of the sample reported that shame, embarrassment, or love were their sole reasons for not calling the police. Underreporting was related to previous (negative) experience with the police, as well as to the level of violence experienced. The practical implications of these findings are discussed.

Immobilized pH gradient two-dimensional gel electrophoresis and mass spectrometric identification of cytokine-regulated proteins in ME-180 cervical carcinoma cells.

Two-dimensional (2-D) polyacrylamide gel electrophoresis combined with mass spectrometry is a powerful combination of technologies that allows high resolution separation of proteins and their rapid identification. Immobilized pH gradient (IPG) first-dimensional gels have several advantages over carrier ampholyte isoelectric focusing, including a high degree of reproducibility, good protein spot resolution, and a selection of pH range. Here we demonstrate the utility and efficacy of combining IPG 2-D gel electrophoresis with mass spectrometry to identify interferon-gamma- (IFN) and tumor necrosis factor (TNF)-regulated proteins in ME-180 cervical carcinoma cells. Three cytokine-regulated proteins have been identified, using imidazole-zinc-stained preparative IPG 2-D gels and in-gel tryptic digestion followed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry for determination of peptide masses and sequences: 1) triosephosphate isomerase, a glycolytic pathway enzyme, 2) proteasome subunit C3, which is important in protein degradation, and 3) Ran, a GTP-binding protein important in cell cycle regulation, protein import into the nucleus, and RNA export from the nucleus.