Ictal Spiking Patterns Recorded from Temporal Depth Electrodes Predict Good Outcome After Anterior Temporal Lobectomy

Purpose : Investigators have shown that the presence of ictal spiking (IS) recorded from temporal depth electrodes is associated with mesial temporal sclerosis (MTS). We investigated the relation of IS to seizure control and pathology after anterior temporal lobectomy (ATL). Methods : All patients undergoing intracranial ictal monitoring from a single institution since 1989 were identified. Those who did not undergo ATL or had postoperative follow-up of <1 year were excluded. All received at a minimum bilateral temporal depth electrodes. Ictal recordings were reviewed for the presence of IS, and the proportion of seizures with IS was determined for each patient. Outcome was determined by using Engel's classification. Surgical specimens were reviewed for pathology. Statistics used were X 2 , Fisher exact test, and Wilcoxon rank sum. Results : Forty patients with 571 seizures were reviewed. In 292 seizures from 32 patients, IS was seen. Outcomes were 24 class I (22 with IS), five class II (four with IS), three class III (one with IS), seven class IV (four with IS), and one lost to follow-up (with IS). Pathologic review revealed 25 with MTS, 22 of whom had IS. The presence of IS was associated with class I outcomes (p = 0.04), but not MTS (p = 0.06). Patients with class I outcomes had a significantly greater proportion of seizures with IS (mean, 0.58 ± 0.3) compared with other outcomes (mean, 0.30 ± 0.3, p = 0.02). Conclusions : The presence of IS and higher proportion of seizures with IS correlated with good seizure outcome after ATL. This information may be used in preoperative counseling.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65542/1/j.1528-1157.2000.tb00161.x.pd

A decade in review: use of data analytics within the biopharmaceutical sector

There are large amounts of data generated within the biopharmaceutical sector. Traditionally, data analysis methods labelled as multivariate data analysis have been the standard statistical technique applied to interrogate these complex data sets. However, more recently there has been a surge in the utilisation of a broader set of machine learning algorithms to further exploit these data. In this article, the adoption of data analysis techniques within the biopharmaceutical sector is evaluated through a review of journal articles and patents published within the last ten years. The papers objectives are to identify the most dominant algorithms applied across different applications areas within the biopharmaceutical sector and to explore whether there is a trend between the size of the data set and the algorithm adopted

High-Throughput Raman Spectroscopy Combined with Innovate Data Analysis Workflow to Enhance Biopharmaceutical Process Development

Raman spectroscopy has the potential to revolutionise many aspects of biopharmaceutical process development. The widespread adoption of this promising technology has been hindered by the high cost associated with individual probes and the challenge of measuring low sample volumes. To address these issues, this paper investigates the potential of an emerging new high-throughput (HT) Raman spectroscopy microscope combined with a novel data analysis workflow to replace off-line analytics for upstream and downstream operations. On the upstream front, the case study involved the at-line monitoring of an HT micro-bioreactor system cultivating two mammalian cell cultures expressing two different therapeutic proteins. The spectra generated were analysed using a partial least squares (PLS) model. This enabled the successful prediction of the glucose, lactate, antibody, and viable cell density concentrations directly from the Raman spectra without reliance on multiple off-line analytical devices and using only a single low-volume sample (50–300 μL). However, upon the subsequent investigation of these models, only the glucose and lactate models appeared to be robust based upon their model coefficients containing the expected Raman vibrational signatures. On the downstream front, the HT Raman device was incorporated into the development of a cation exchange chromatography step for an Fc-fusion protein to compare different elution conditions. PLS models were derived from the spectra and were found to predict accurately monomer purity and concentration. The low molecular weight (LMW) and high molecular weight (HMW) species concentrations were found to be too low to be predicted accurately by the Raman device. However, the method enabled the classification of samples based on protein concentration and monomer purity, allowing a prioritisation and reduction in samples analysed using A280 UV absorbance and high-performance liquid chromatography (HPLC). The flexibility and highly configurable nature of this HT Raman spectroscopy microscope makes it an ideal tool for bioprocess research and development, and is a cost-effective solution based on its ability to support a large range of unit operations in both upstream and downstream process operations

A mixed methods study to evaluate the feasibility of using the Adolescent Diabetes Needs Assessment Tool App in paediatric diabetes care in preparation for a longitudinal cohort study

An evaluation study was carried out to determine the feasibility of integrating the Adolescent Diabetes Needs Assessment Tool (ADNAT) App into UK paediatric diabetes care, to ascertain best practice standards and to determine methodological recommendations for a future cohort study. Methods A non-randomised, cohort, mixed methods study design was used to ensure equality of access to ADNAT for all participants at three sites in the North West of England. Following UK Medical Research Council guidance, the RE-AIM (reach, effectiveness (potential and perceived), adoption, implementation, maintenance) framework was used to guide study objectives and feasibility outcomes. Patients who completed ADNAT (completers) were compared with those who failed to complete (non-completers). Patients’ glycaemic control (HbA1c) was accessed from their clinical data at baseline and at 6 months, alongside their ADNAT scores which were correlated with changes in HbA1c levels. The diabetes teams (respondents) completed a web-based survey and attended focus group interviews. Results Eighty-nine patients were recruited. Withdrawal rates were low at 4.5% (n = 4). Forty-four patients (49.4%) completed ADNAT, leaving 45 (50.6%) non-completers. There were large baseline differences in HbA1c and variable rates of change at 6 months. After adjusting for baseline HbA1C and site in an analysis of covariance, completers had a lower post-ADNAT mean HbA1C level than non-completers at 6 months (-5.42 mmol/mol, 95% CI −11.48, 0.64). Patients’ glycaemic control (HbA1c) at 6 months correlated reasonably well with their ADNAT scores (Spearman’s rho = 0.46). Survey and focus group data showed that ADNAT was judged to be an effective clinical tool by the diabetes teams. Value to patients was perceived by the teams to be linked to parental support, age and previous diabetes education. The combined data triangulated. It served to capture different dimensions which were used to define changes to achieve practice standards and methodological recommendations. Conclusions The combined data showed that ADNAT has the potential to be a clinically viable tool. It has demonstrated the need for a randomised design that is tailored for a ‘hard to reach’ adolescent population. A cluster randomised controlled trial that involves sequential but random rollout of ADNAT over multiple time periods may be the most appropriate and is currently being considered for the larger study

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Propagation of Epileptiform Events across the Corpus Callosum in a Cingulate Cortical Slice Preparation

We report on a novel mouse in vitro brain slice preparation that contains intact callosal axons connecting anterior cingulate cortices (ACC). Callosal connections are demonstrated by the ability to regularly record epileptiform events between hemispheres (bilateral events). That the correlation of these events depends on the callosum is demonstrated by the bisection of the callosum in vitro. Epileptiform events are evoked with four different methods: (1) bath application of bicuculline (a GABA-A antagonist); (2) bicuculline+MK801 (an NMDA receptor antagonist), (3) a zero magnesium extracellular solution (0Mg); (4) focal application of bicuculline to a single cortical hemisphere. Significant increases in the number of epileptiform events, as well as increases in the ratio of bilateral events to unilateral events, are observed during bath applications of bicuculline, but not during applications of bicuculline+MK-801. Long ictal-like events (defined as events >20 seconds) are only observed in 0Mg. Whole cell patch clamp recordings of single neurons reveal strong feedforward inhibition during focal epileptiform events in the contralateral hemisphere. Within the ACC, we find differences between the rostral areas of ACC vs. caudal ACC in terms of connectivity between hemispheres, with the caudal regions demonstrating shorter interhemispheric latencies. The morphologies of many patch clamped neurons show callosally-spanning axons, again demonstrating intact callosal circuits in this in vitro preparation

Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence

Prevalence of overweight in children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorders: a chart review

BACKGROUND: The condition of obesity has become a significant public health problem in the United States. In children and adolescents, the prevalence of overweight has tripled in the last 20 years, with approximately 16.0% of children ages 6–19, and 10.3% of 2–5 year olds being considered overweight. Considerable research is underway to understand obesity in the general pediatric population, however little research is available on the prevalence of obesity in children with developmental disorders. The purpose of our study was to determine the prevalence of overweight among a clinical population of children diagnosed with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). METHODS: Retrospective chart review of 140 charts of children ages 3–18 years seen between 1992 and 2003 at a tertiary care clinic that specializes in the evaluation and treatment of children with developmental, behavioral, and cognitive disorders. Diagnostic, medical, and demographic information was extracted from the charts. Primary diagnoses of either ADHD or ASD were recorded, as was information on race/ethnicity, age, gender, height, and weight. Information was also collected on medications that the child was taking. Body mass index (BMI) was calculated from measures of height and weight recorded in the child's chart. The Center for Disease Control's BMI growth reference was used to determine an age- and gender-specific BMI z-score for the children. RESULTS: The prevalence of at-risk-for-overweight (BMI >85th%ile) and overweight (BMI > 95th%ile) was 29% and 17.3% respectively in children with ADHD. Although the prevalence appeared highest in the 2–5 year old group (42.9%ile), differences among age groups were not statistically significant. Prevalence did not differ between boys and girls or across age groups (all p > 0.05). For children with ASD, the overall prevalence of at-risk-for-overweight was 35.7% and prevalence of overweight was 19%. CONCLUSION: When compared to an age-matched reference population (NHANES 1999–2002), our estimates indicate that children with ADHD and with ASD have a prevalence of overweight that is similar to children in the general population

Type D personality is associated with increased metabolic syndrome prevalence and an unhealthy lifestyle in a cross-sectional Dutch community sample

<p>Abstract</p> <p>Background</p> <p>People with Type D-Distressed-personality have a general tendency towards increased negative affectivity (NA), while at the same time inhibiting these emotions in social situations (SI). Type D personality is associated with an increased risk of adverse outcomes in patients with cardiovascular disease. Whether Type D personality is a cardiovascular risk factor in healthy populations remains to be investigated. In the present study, the relations between Type D personality and classical cardiovascular risk factors, i.e. metabolic syndrome and lifestyle were investigated in a Dutch community sample.</p> <p>Methods</p> <p>In a cross-sectional study 1592 participants were included, aged 20-80 years. Metabolic syndrome was defined by self-report, following the International Diabetes Federation-IDF-guidelines including an increased waist circumference, dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking, alcohol use, exercise and dietary habits were examined. Metabolic syndrome prevalence was stratified by Type D personality (a high score on both NA and SI), lifestyle and confounders age, gender, having a partner, higher education level, cardiac history, family history of cardiovascular disease.</p> <p>Results</p> <p>Metabolic syndrome was more prevalent in persons with a Type D personality (13% vs. 6%). Persons with Type D personality made poorer lifestyle choices, adhered less to the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, <it>p </it>= .02), had a less varied diet (OR = 0.50, 95%CI = 0.40-0.70, <it>p </it>< .0005), and were less likely to restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, <it>p </it>= .01). Type D personality was related to a twofold increased risk of metabolic syndrome (OR = 2.2, 95%CI = 1.2-4.0, <it>p </it>= .011), independent of lifestyle factors and confounders.</p> <p>Conclusions</p> <p>Type D personality is related to an increased prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both behavioral and biological vulnerability for development of cardiovascular disorders and diabetes.</p

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children