Search

Objective: This study investigated why certain embedded performance validity indicators (EVIs) are prone to higher false-positive rates (FPRs) in attention-deficit/hyperactivity disorder (ADHD) evaluations. The first aim was to establish the relationship between FPRs and 15 EVIs derived from six cognitive tests when used independently and together among adults with ADHD who have valid test performance. The second aim was to determine which specific EVIs increase the FPRs in this population., Method: Participants were 517 adult ADHD referrals with valid neurocognitive test performance as determined by multiple performance validity tests and established empirical criteria. FPRs were defined by the proportion of participants who scored below an empirically established EVI cutoff with ≥0.90 specificity., Results: EVIs derived from two of the six tests exhibited unacceptably high FPRs (>10%) when used independently, but the total FPR decreased to 8.1% when the EVIs were aggregated. Several EVIs within a sustained attention test were associated with FPRs around 11%. EVIs that did not include demographically adjusted cutoffs, specifically for race, were associated with higher FPRs around 14%. Conversely, FPRs did not significantly differ based on whether EVIs included timed versus untimed, verbal versus nonverbal, or graphomotor versus non-graphomotor components, nor whether they had raw versus standardized cut scores., Conclusions: Findings suggest that practitioners should consider both the type of test from which an EVI is derived and the aggregate number of EVIs employed to minimize the FPRs in ADHD evaluations. Findings also indicate that more nuanced approaches to validity test selection and development are needed., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease., Objective: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began., Methods: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs., Results: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10 -35 and P = 1.1 × 10 -24 , respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6-inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors., Conclusions: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Objective: This study investigated whether extreme cut-scores on the Barkley Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale-Fourth Edition (BAARS-IV) self-report scales could serve as symptom overreporting indicators in adult ADHD evaluations. Method: The sample consisted of 162 adults who underwent a neuropsychological evaluation for ADHD. Patients were classified into valid ( n  = 115) and invalid ( n  = 47) groups based on multiple criterion symptom validity tests. Results: Overreporting cut-scores identified for each of the BAARS-IV scales demonstrated acceptable classification accuracy or better. The Current Total scale yielded the highest classification accuracy (area under the curve of .83). An optimal raw cut-score of ≥56 for this scale yielded 47% sensitivity when upholding ≥90% specificity. A cut-score of ≥31 for the Current Inattention scale (90% specificity; 47% sensitivity) and ≥29 for the Current Sluggish Cognitive Tempo scale (88% specificity; 46% sensitivity) were also relatively strong indicators of overreporting. The Current Total and Current Sluggish Cognitive Tempo scales captured nonredundant aspects of symptom validity, and using them together increased sensitivity to 57% while maintaining ≥90% specificity. Conclusions: Findings provide preliminary support for the criterion and construct validity of extreme cut-scores on the BAARS-IV Current Sluggish Cognitive Tempo, Current Inattention, and Current Total scales as indicators of ADHD symptom overreporting. However, employing the cut-scores from the Current Sluggish Cognitive Tempo (≥29) and Current Total (≥56) together may be the most promising way to detect overreporting. Scores above both of these cut-points should, at a minimum, prompt further investigation into the validity of a patient's reported symptoms.

Objective: This study investigated the relationship between processing speed impairment severity and performance on the Rey 15-Item Test (RFIT) and RFIT + Recognition., Method: Cross-sectional data from 285 examinees (228 valid/57 invalid) referred for neuropsychological assessment who were administered the RFIT, Weschler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Processing Speed Index (PSI), Brief Visuospatial Memory Test - Revised, Rey Auditory Verbal Learning Test, and three independent criterion PVTs were included. PSI bands were operationalized as Intact (≥85SS; n  = 163), Reduced/Possibly Impaired (77-84SS; n  = 36), or Impaired (≤76 SS; n  = 29). Receiver operator characteristic (ROC) curve analyses tested the RFIT and RFIT + Recognition's classification accuracy for detecting invalid performance for the overall sample and by PSI impairment status., Results: Those with intact processing speed performed significantly better on the RFIT and RFIT + Recognition than those with reduced/possibly impaired and impaired processing speed. Though verbal/visual memory predicted RFIT scores independently, PSI contributed additional variance. ROC curves for RFIT and RFIT + Recognition were significant (AUC=.64-.84). Optimal cut-scores yielded modest sensitivity (30%-63%) and high specificity (89%-93%) among those with intact and reduced processing speed but yielded unacceptable accuracy in those with impaired speed (AUC=.59-.62)., Conclusions: Although the RFIT and RFIT + Recognition demonstrated acceptable classification accuracy in those with intact processing speed, accuracy diminished with increasing speed impairment. This finding was more pronounced for RFIT + Recognition compared to the traditional RFIT. As such, the RFIT may have limited clinical utility in examinees with more significant processing speed deficits.

Objectives: This study investigated the relationship between various intrapersonal factors and the discrepancy between subjective and objective cognitive difficulties in adults with attention-deficit hyperactivity disorder (ADHD). The first aim was to examine these associations in patients with valid cognitive symptom reporting. The next aim was to investigate the same associations in patients with invalid scores on tests of cognitive symptom overreporting., Method: The sample comprised 154 adults who underwent a neuropsychological evaluation for ADHD. Patients were divided into groups based on whether they had valid cognitive symptom reporting and valid test performance ( n = 117) or invalid cognitive symptom overreporting but valid test performance ( n = 37). Scores from multiple symptom and performance validity tests were used to group patients. Using patients' scores from a cognitive concerns self-report measure and composite index of objective performance tests, we created a subjective-objective discrepancy index to quantify the extent of cognitive concerns that exceeded difficulties on objective testing. Various measures were used to assess intrapersonal factors thought to influence the subjective-objective cognitive discrepancy, including demographics, estimated premorbid intellectual ability, internalizing symptoms, somatic symptoms, and perceived social support., Results: Patients reported greater cognitive difficulties on subjective measures than observed on objective testing. The discrepancy between subjective and objective scores was most strongly associated with internalizing and somatic symptoms. These associations were observed in both validity groups., Conclusions: Subjective cognitive concerns may be more indicative of the extent of internalizing and somatic symptoms than actual cognitive impairment in adults with ADHD, regardless if they have valid scores on cognitive symptom overreporting tests.

The para hydrogen-induced polarisation (PHIP) NMR signal enhancement technique is used to study H 2 addition to Vaska's complex ( trans -[IrCl(CO)(PPh 3 ) 2 ]) with both standard high-field (9.4 T) NMR and benchtop (1 T) NMR detection. Accurate and repeatable rate constants of (0.84 ± 0.03) dm 3 mol -1 s -1 and (0.89 ± 0.03) dm 3 mol -1 s -1 were obtained for this model system using standard high-field and benchtop NMR, respectively. The high-field NMR approach is shown to be susceptible to systematic errors associated with interference from non-hyperpolarised signals, which can be overcome through a multiple-quantum filtered acquisition scheme. This challenge is avoided when using benchtop NMR detection because the non-hyperpolarised signals are much weaker due to the lower magnetic field, enabling the use of a simpler and more efficient single RF pulse detection scheme. Method validation against several experimental parameters (NMR relaxation, % p H 2 enrichment and temperature) demonstrates the robustness of the benchtop NMR approach but also highlights the need for sample temperature control throughout reaction monitoring. A simple temperature equilibration protocol, coupled with use of an insulated sample holder while manipulating the sample outside the spectrometer, is found to provide sufficient temperature stabilisation to ensure that accurate and repeatable rate constants are obtained. Finally, the benchtop NMR reaction monitoring protocol is applied to the analysis of a complex mixture, where multiple reaction products form simultaneously. H 2 addition to a mixture of three Vaska's complex derivatives was monitored, revealing the presence of competitive reaction pathways within the mixture.

Isoprene is a key trace component of the atmosphere emitted by vegetation and other organisms. It is highly reactive and can impact atmospheric composition and climate by affecting the greenhouse gases ozone and methane and secondary organic aerosol formation. Marine fluxes are poorly constrained due to the paucity of long-term measurements; this in turn limits our understanding of isoprene cycling in the ocean. Here we present the analysis of isoprene concentrations in the atmosphere measured across the Southern Ocean over 4 months in the summertime. Some of the highest concentrations ( >500 ppt) originated from the marginal ice zone in the Ross and Amundsen seas, indicating the marginal ice zone is a significant source of isoprene at high latitudes. Using the United Kingdom Earth System Model we show that current estimates of sea-to-air isoprene fluxes underestimate observed isoprene by a factor >20. A daytime source of isoprene is required to reconcile models with observations. The model presented here suggests such an increase in isoprene emissions would lead to >8% decrease in the hydroxyl radical in regions of the Southern Ocean, with implications for our understanding of atmospheric oxidation and composition in remote environments, often used as proxies for the pre-industrial atmosphere., (© 2024. The Author(s).)

Surfactants can aid subsurface remediation through three primary mechanisms - solubilization, mobilization and/or emulsification. Among these mechanisms, emulsification in porous media is generally not well studied or well understood; particularly in the context of treating sources containing multicomponent NAPL. The objective of this research was to elucidate the processes responsible for recovery of a multicomponent hydrocarbon NAPL when surfactant solutions are introduced within a porous medium to promote the formation of kinetically-stable oil-in-water emulsions. Emulsifier formulations considered here were selected to offer similar performance characteristics while relying on different families of non-ionic surfactants - nonylphenol ethoxylates or alcohol ethoxylates - for emulsification. The families of surfactants have particular environment relevance, as alcohol ethoxylates are often used where replacement of nonylphenol content is necessary. Results from batch and column studies suggest performance of the two formulations was similar. With both, a synergistic combination of emulsification and mobilization led to recovery of a synthetic gasoline NAPL. The relative contribution of solubilization to the recovery was found to be minor. Moreover, the physical processes associated with emulsification and mobilization acted to limit the amount of preferential recovery (or fractionation) of the multicomponent NAPL., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ramsburg reports financial support was provided by Biosolve. Ramsburg is on editorial board for JCH., (Copyright © 2023. Published by Elsevier B.V.)

Metastatic urothelial carcinoma is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, with ARID1A-inactivating mutations present in about 20% of tumors. EZH2, a histone methyltransferase, acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling is activated in more than 20% of bladder cancers. Using a combination of in vitro and in vivo data, including patient-derived xenografts, we show that ARID1A-mutant tumors were more sensitive to EZH2 inhibition than ARID1A WT tumors. Mechanistic studies revealed that (a) ARID1A deficiency results in a dependency on PI3K/AKT/mTOR signaling via upregulation of a noncanonical PI3K regulatory subunit, PIK3R3, and downregulation of MAPK signaling and (b) EZH2 inhibitor sensitivity is due to upregulation of PIK3IP1, a protein inhibitor of PI3K signaling. We show that PIK3IP1 inhibited PI3K signaling by inducing proteasomal degradation of PIK3R3. Furthermore, ARID1A-deficient bladder cancer was sensitive to combination therapies with EZH2 and PI3K inhibitors in a synergistic manner. Thus, our studies suggest that bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K and revealed mechanistic insights into the role of noncanonical PI3K constituents in bladder cancer biology.

Lung cancer is the leading cause of cancer-related deaths globally and is histologically defined as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC), with the latter accounting for 80% of all lung cancers. The 5-year overall survival rate for lung cancer patients is low as it is often discovered at advanced stages when potential cure by surgical resection is no longer an option. To identify a biomarker and target for lung cancer, we performed analysis of multiple datasets of lung cancer gene expression data. Our analyses indicated that the collagen-modifying enzyme Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is overexpressed in NSCLC. Furthermore, our investigation found that overexpression of enzymes involved in this pathway predicts poor outcome for patients with lung adenocarcinoma. Our functional studies using knockdown strategies in lung cancer cell lines in vitro indicated that P4HA1 is critical for lung cancer growth, migration, and invasion. Additionally, diethyl pythiDC (PythiDC), a small molecule inhibitor, decreased the malignant phenotypes of lung cancer cells. Moreover, we found that miR-124 regulates and targets P4HA1 in lung cancer cells. Thus, our study suggests that collagen-modifying enzymes play an important role in lung cancer aggressiveness. Furthermore, our studies showed that P4HA1 is required for lung cancer cell growth and invasion, suggesting its potential as a valid therapeutic target in lung adenocarcinoma., (Copyright © 2021. Published by Elsevier Inc.)

Muscle-invasive bladder carcinomas (MIBCs) are aggressive genitourinary malignancies. Metastatic urothelial carcinoma of the bladder is generally incurable by current chemotherapy and leads to early mortality. Recent studies have identified molecular subtypes of MIBCs with different sensitivities to frontline therapy, suggesting tumor heterogeneity. We have performed multi-omic profiling of the kinome in bladder cancer patients with the goal of identify therapeutic targets. Our analyses revealed amplification, overexpression, and elevated kinase activity of P21 (RAC1) activated kinase 4 (PAK4) in a subset of Bladder cancer (BLCA). Using bladder cancer cells, we confirmed the role of PAK4 in BLCA cell proliferation and invasion. Furthermore, we observed that a PAK4 inhibitor was effective in curtailing growth of BLCA cells. Transcriptomic analyses identified elevated expression of another kinase, protein tyrosine kinase 6 (PTK6), upon treatment with a PAK4 inhibitor and RNA interference of PAK4. Treatment with a combination of kinase inhibitors (vandetanib and dasatinib) showed enhanced sensitivity compared with either drug alone. Thus, PAK4 may be therapeutically actionable for a subset of MIBC patients with amplified and/or overexpressed PAK4 in their tumors. Our results also indicate that combined inhibition of PAK4 and PTK6 may overcome resistance to PAK4. These observations warrant clinical investigations with selected BLCA patients.

Objective: To examine parent's perceptions of deep brain stimulation (DBS) and whether DBS is perceived to be a viable and safe treatment for their adolescent child presenting with a severe, treatment-resistant neurological or psychiatric condition. Method: Two hundred and seventy-nine parents completed an online survey using Amazon Mechanical Turk (MTurk). Participants were presented with five vignette scenarios involving adolescents with severe, treatment-resistant neurological or psychiatric conditions: Rett syndrome, autism spectrum disorder, epilepsy, obsessive-compulsive disorder, and Tourette syndrome. Parents were then asked to evaluate each scenario and rate overall acceptability of using DBS to improve their child's core symptoms. Data were collected over a period of 2 weeks in the month of October 2018. Results: We found that parents reported favorable impressions of DBS regardless of the target condition, especially when greater improvement could be assured and when their child had the capacity to assist in the treatment decision-making. Parents indicated some reluctance to use DBS when possible safety concerns were present. Familiarity with DBS was directly associated with attitudes. Conclusions: The findings highlight an overall parental willingness to consider DBS as a treatment option for key symptoms of neurological and psychiatric conditions in adolescents.

Cancer is a disease of uncontrolled cell growth and a major cause of death worldwide. Many molecular events characterize tumor initiation and progression. Global gene expression analyses using next-generation sequencing, proteomics and metabolomics show genomic, epigenetic, and metabolite concentration changes in various tumors. Molecular alterations identified include multiple cancer-driving mutations, gene fusions, amplifications, deletions, and post-translational modifications. Data integration from many high-throughput platforms unraveled dysregulation in many metabolic pathways in cancer. Since cancer cells are fast-growing, their metabolic needs are enhanced, hence the requirement for de novo synthesis of essential metabolites. One critical requirement of fast-growing cells and a historically important pathway in cancer is the nucleotide biosynthetic pathway and its enzymes are valuable targets for small molecule inhibition. Purines and pyrimidines are building blocks of DNA synthesis and due to their excessive growth, cancer cells extensively utilize de novo pathways for nucleotide biosynthesis. Methotrexate, one of the early chemotherapeutic agents, targets dihydrofolate reductase of the folate metabolic pathway that is involved in nucleotide biosynthesis. In this review, we discuss the nucleotide biosynthetic pathways in cancer and targeting opportunities., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Recent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine-N-acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen., Method: We performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high-density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA-sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways., Results: Our in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers had higher GLYATL1 expression compared to high-grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways., Conclusions: In summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings., (© 2019 Wiley Periodicals, Inc.)

The detection of alcohols by magnetic resonance techniques is important for their characterization and the monitoring of chemical change. Hyperpolarization processes can make previously inpractical measurements, such as the determination of low concentration intermediates, possible. Here, we investigate the SABRE-Relay method in order to define its key characteristics and improve the resulting 1 H NMR signal gains which subsequently approach 10 3 per proton. We identify optimal amine proton transfer agents for SABRE-Relay and show how catalyst structure influences the outcome. The breadth of the method is revealed by expansion to more complex alcohols and the polarization of heteronuclei., (This journal is © The Royal Society of Chemistry 2019.)

Objective: To assess the efficacy of transdermal lidocaine as a treatment for chronic subjective tinnitus as measured by the Tinnitus Functional Index (TFI)., Study Design: Pilot, prospective efficacy trial., Setting: Tertiary care hospital., Patients: Men and women, over the age of 18 with chronic subjective tinnitus for >6 months., Intervention: Daily application of commercially available transdermal lidocaine patch., Outcome Measure: Change in the TFI., Results: The average pre-treatment TFI score was 56.2. After 1 month the average TFI decreased to 41 (p < 0.05). The scores dropped to 34 and 35 after 2 and 3 months of treatment respectively. Despite improvement in symptoms of tinnitus, most patients did not continue the study after the first month, dropping out due to the size, discomfort, and appearance of the lidocaine patch, failure to follow-up and lack of perceived benefit from treatment., Conclusions: In this preliminary study, 5% transdermal lidocaine appears to be a potential treatment for chronic subjective tinnitus. The majority of subjects who completed 1 month of treatment had clinically significantly improved tinnitus. These findings are confounded however by the small sample size and significant drop out rate., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overexpression of ERG in the majority of prostate cancers. Overexpression of ERG plays a critical role in prostate oncogenesis and development of metastatic disease. Among the downstream effectors of ERG, Frizzled family member FZD4 has been shown to be a target of ERG. Frizzled-8 (FZD8) has been shown to be involved in PCa bone metastasis. In the present study, we show that the expression of FZD8 is directly correlated with ERG expression in PCa. Furthermore, we show that ERG directly targets and activates FZD8 by binding to its promoter. This activation is specific to ETS transcription factor ERG and not ETV1. We propose that ERG overexpression in PCa leads to induction of Frizzled family member FZD8, which is known to activate the Wnt pathway. Taken together, these findings uncover a novel mechanism for PCa metastasis, and indicate that FZD8 may represent a potential therapeutic target for PCa., (© 2018 Wiley Periodicals, Inc.)

Objectives: (1) Identify knowledge deficits in this cohort regarding basic conditions treated by an otolaryngologist. (2) Determine the training needs of these physicians regarding the care of the head and neck patient., Methods: This cross-sectional assessment used a 10-question, multiple-choice assessment administered to medical students and resident physicians at the University of California, Davis, University of California, San Francisco, and University of West Virginia in the departments of emergency medicine, family medicine, internal medicine, and otolaryngology., Results: The otolaryngology cohort scored an average of 93%, while all others scored 56%. There was no statistical difference in the results between fourth-year medical students and non-otolaryngology residents of any year. Only 16% of the primary care providers and students assessed felt comfortable with these conditions, and 86% (321/372) of the respondents desired increased education on these topics., Conclusion: This study identified significant knowledge gaps among non-otolaryngologists in the diagnosis and treatment of basic head and neck conditions. As a specialty, a greater focus should be placed on improving the familiarity of our primary care colleagues on these conditions.

The chemical breakdown of organic matter in landfills represents a significant source of methane gas (CH 4 ). Current estimates suggest that landfills are responsible for between 3% and 19% of global anthropogenic emissions. The net CH 4 emissions resulting from biogeochemical processes and their modulation by microbes in landfills are poorly constrained by imprecise knowledge of environmental constraints. The uncertainty in absolute CH 4 emissions from landfills is therefore considerable. This study investigates a new method to estimate the temporal variability of CH 4 emissions using meteorological and CH 4 concentration measurements downwind of a landfill site in Suffolk, UK from July to September 2014, taking advantage of the statistics that such a measurement approach offers versus shorter-term, but more complex and instantaneously accurate, flux snapshots. Methane emissions were calculated from CH 4 concentrations measured 700m from the perimeter of the landfill with observed concentrations ranging from background to 46.4ppm. Using an atmospheric dispersion model, we estimate a mean emission flux of 709μgm -2 s -1 over this period, with a maximum value of 6.21mgm -2 s -1 , reflecting the wide natural variability in biogeochemical and other environmental controls on net site emission. The emissions calculated suggest that meteorological conditions have an influence on the magnitude of CH 4 emissions. We also investigate the factors responsible for the large variability observed in the estimated CH 4 emissions, and suggest that the largest component arises from uncertainty in the spatial distribution of CH 4 emissions within the landfill area. The results determined using the low-maintenance approach discussed in this paper suggest that a network of cheaper, less precise CH 4 sensors could be used to measure a continuous CH 4 emission time series from a landfill site, something that is not practical using far-field approaches such as tracer release methods. Even though there are limitations to the approach described here, this easy, low-maintenance, low-cost method could be used by landfill operators to estimate time-averaged CH 4 emissions and their impact downwind by simultaneously monitoring plume advection and CH 4 concentrations., (Copyright © 2016. Published by Elsevier Ltd.)

The Antarctic continent is known to be an unpopulated region due to its extreme weather and climate conditions. However, the air quality over this continent can be affected by long-lived anthropogenic pollutants from the mainland. The Argentinian region of Ushuaia is often the main source area of accumulated hazardous gases over the Antarctic Peninsula. The main objective of this study is to report the first in situ observations yet known of surface ozone (O 3 ) over Ushuaia, the Drake Passage, and Coastal Antarctic Peninsula (CAP) on board the RV Australis during the Malaysian Antarctic Scientific Expedition Cruise 2016 (MASEC'16). Hourly O 3 data was measured continuously for 23 days using an EcoTech O 3 analyzer. To understand more about the distribution of surface O 3 over the Antarctic, we present the spatial and temporal of surface O 3 of long-term data (2009-2015) obtained online from the World Meteorology Organization of World Data Centre for greenhouse gases (WMO WDCGG). Furthermore, surface O 3 satellite data from the free online NOAA-Atmospheric Infrared Sounder (AIRS) database and online data assimilation from the European Centre for Medium-Range Weather Forecasts (ECMWF)-Monitoring Atmospheric Composition and Climate (MACC) were used. The data from both online products are compared to document the data sets and to give an indication of its quality towards in situ data. Finally, we used past carbon monoxide (CO) data as a proxy of surface O 3 formation over Ushuaia and the Antarctic region. Our key findings were that the surface O 3 mixing ratio during MASEC'16 increased from a minimum of 5 ppb to ~ 10-13 ppb approaching the Drake Passage and the Coastal Antarctic Peninsula (CAP) region. The anthropogenic and biogenic O 3 precursors from Ushuaia and the marine region influenced the mixing ratio of surface O 3 over the Drake Passage and CAP region. The past data from WDCGG showed that the annual O 3 cycle has a maximum during the winter of 30 to 35 ppb between June and August and a minimum during the summer (January to February) of 10 to 20 ppb. The surface O 3 mixing ratio during the summer was controlled by photochemical processes in the presence of sunlight, leading to the depletion process. During the winter, the photochemical production of surface O 3 was more dominant. The NOAA-AIRS and ECMWF-MACC analysis agreed well with the MASEC'16 data but twice were higher during the expedition period. Finally, the CO past data showed the surface O 3 mixing ratio was influenced by the CO mixing ratio over both the Ushuaia and Antarctic regions. Peak surface O 3 and CO hourly mixing ratios reached up to ~ 38 ppb (O 3 ) and ~ 500 ppb (CO) over Ushuaia. High CO over Ushuaia led to the depletion process of surface O 3 over the region. Monthly CO mixing ratio over Antarctic (South Pole) were low, leading to the production of surface O 3 over the Antarctic region.

Malaysian Borneo has a lower population density and is an area known for its lush rainforests. However, changes in pollutant profiles are expected due to increasing urbanisation and commercial-industrial activities. This study aims to determine the variation of surface O 3 concentration recorded at seven selected stations in Malaysian Borneo. Hourly surface O 3 data covering the period 2002 to 2013, obtained from the Malaysian Department of Environment (DOE), were analysed using statistical methods. The results show that the concentrations of O 3 recorded in Malaysian Borneo during the study period were below the maximum Malaysian Air Quality Standard of 100ppbv. The hourly average and maximum O 3 concentrations of 31 and 92ppbv reported at Bintulu (S3) respectively were the highest among the O 3 concentrations recorded at the sampling stations. Further investigation on O 3 precursors show that sampling sites located near to local petrochemical industrial activities, such as Bintulu (S3) and Miri (S4), have higher NO 2 /NO ratios (between 3.21 and 5.67) compared to other stations. The normalised O 3 values recorded at all stations were higher during the weekend compared to weekdays (unlike its precursors) which suggests the influence of O 3 titration by NO during weekdays. The results also show that there are distinct seasonal variations in O 3 across Borneo. High surface O 3 concentrations were usually observed between August and September at all stations with the exception of station S7 on the east coast. Majority of the stations (except S1 and S6) have recorded increasing averaged maximum concentrations of surface O 3 over the analysed years. Increasing trends of NO 2 and decreasing trends of NO influence the yearly averaged maximum of O 3 especially at S3. This study also shows that variations of meteorological factors such as wind speed and direction, humidity and temperature influence the concentration of surface O 3 ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

MicroRNA-101, a tumor suppressor microRNA (miR), is often downregulated in cancer and is known to target multiple oncogenes. Some of the genes that are negatively regulated by miR-101 expression include histone methyltransferase EZH2 (enhancer of zeste homolog 2), COX2 (cyclooxygenase-2), POMP (proteasome maturation protein), CERS6, STMN1, MCL-1 and ROCK2, among others. In the present study, we show that miR-101 targets transcriptional coactivator SUB1 homolog (Saccharomyces cerevisiae)/PC4 (positive cofactor 4) and regulates its expression. SUB1 is known to have diverse role in vital cell processes such as DNA replication, repair and heterochromatinization. SUB1 is known to modulate transcription and acts as a mediator between the upstream activators and general transcription machinery. Expression profiling in several cancers revealed SUB1 overexpression, suggesting a potential role in tumorigenesis. However, detailed regulation and function of SUB1 has not been elucidated. In this study, we show elevated expression of SUB1 in aggressive prostate cancer. Knockdown of SUB1 in prostate cancer cells resulted in reduced cell proliferation, invasion and migration in vitro, and tumor growth and metastasis in vivo. Gene expression analyses coupled with chromatin immunoprecipitation revealed that SUB1 binds to the promoter regions of several oncogenes such as PLK1 (Polo-like kinase 1), C-MYC, serine-threonine kinase BUB1B and regulates their expression. Additionally, we observed SUB1 downregulated CDKN1B expression. PLK1 knockdown or use of PLK1 inhibitor can mitigate oncogenic function of SUB1 in benign prostate cancer cells. Thus, our study suggests that miR-101 loss results in increased SUB1 expression and subsequent activation of known oncogenes driving prostate cancer progression and metastasis. This study therefore demonstrates functional role of SUB1 in prostate cancer, and identifies its regulation and potential downstream therapeutic targets of SUB1 in prostate cancer., Competing Interests: of Potential Conflicts of Interest The authors declare no competing financial interests. Correspondence and requests for materials should be addressed to S.V.

Purpose: To identify which patients and canines are involved in dog bites of the head and neck, and how they impact health systems., Materials and Methods: This is a single center, retrospective cohort study conducted from January 2012 to June 2013 in an academic, tertiary care center situated between multiple suburban and urban communities. Patients were identified by queried search for all bite-related diagnoses codes., Results: 334 unique dog bites were identified, of which 101 involved the head and neck. The mean patient age was 15.1±18.1years. Of the more than 8 different breeds identified, one-third were caused by pit bull terriers and resulted in the highest rate of consultation (94%) and had 5 times the relative rate of surgical intervention. Unlike all other breeds, pit bull terriers were relatively more likely to attack an unknown individual (+31%), and without provocation (+48%). Injuries of the head and neck had an average follow-up of 1.26±2.4 visits, and average specialty follow-up of 3.1±3.5 visits., Conclusions: The patients most likely to suffer dog bite injuries of the head and neck are children. Although a number of dog breeds were identified, the largest group were pit bull terriers, whose resultant injuries were more severe and resulted from unprovoked, unknown dogs. More severe injuries required a greater number of interventions, a greater number of inpatient physicians, and more outpatient follow-up encounters. Healthcare utilization and costs associated with dog bites warrant further investigation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose of Review: To examine the current literature regarding application of cochlear implantation in patients with single-sided deafness for improvement in sound localization., Recent Findings: As familiarity of the technical and biological capabilities of cochlear implantation improves and criteria for use broaden, investigators have begun examining usage of cochlear implantation in patients with single-sided deafness as a viable solution in attempts to improve sound localization and speech perception. Although studies of such application are limited, from the available published literature, modest benefits have been described in both sound localization and speech perception. Patients consistently report improvement in quality of life after cochlear implantation for single-sided deafness., Summary: Although single-sided deafness is not a currently approved indication for cochlear implantation, limited investigational studies to date have demonstrated patient improvement in both sound localization and speech perception.

We present results from the OP3 campaign in Sabah during 2008 that allow us to study the impact of local emission changes over Borneo on atmospheric composition at the regional and wider scale. OP3 constituent data provide an important constraint on model performance. Treatment of boundary layer processes is highlighted as an important area of model uncertainty. Model studies of land-use change confirm earlier work, indicating that further changes to intensive oil palm agriculture in South East Asia, and the tropics in general, could have important impacts on air quality, with the biggest factor being the concomitant changes in NO(x) emissions. With the model scenarios used here, local increases in ozone of around 50 per cent could occur. We also report measurements of short-lived brominated compounds around Sabah suggesting that oceanic (and, especially, coastal) emission sources dominate locally. The concentration of bromine in short-lived halocarbons measured at the surface during OP3 amounted to about 7 ppt, setting an upper limit on the amount of these species that can reach the lower stratosphere.

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital condition in which a genetic female is born with vaginal agenesis and a rudimentary to absent uterus. This condition affects a woman's ability to menstruate, to engage in penile-vaginal intercourse, and to bear children. Much has been published about how best to create a neovagina in women with MRKH, but little has been written about the psychological impact of MRKH and quality of life outcomes for women with the condition. A review of the extant literature published from 1955 to 2007 supports that (1) surgical or non-surgical creation of a neovagina alone does not ensure a successful psychological outcome, (2) psychological support at critical times can be helpful, and (3) how professionals use language to discuss the condition may positively or negatively influence a female's experience of MRKH. This article discusses the implications that existing knowledge has on future research and on clinical practice. Understanding how women with MRKH cope with and adjust to the condition will help healthcare professionals provide optimal care.

Studies of adolescent female sexuality often focus on coitus to the exclusion of noncoital behaviors, the relational context of sexual interactions, and adolescent women's subjective perceptions of their experiences. In this study, 38 undergraduate women's retrospective accounts of their adolescent heterosexual experiences were examined. Generalized estimating equation models were used to test the relation of diverse heterosexual behaviors and relationship types to participants' subjective perceptions of desire, wanting, and pleasure. Of the sexual behaviors, coitus was the strongest predictor of participants' subjective perceptions. Compared to coitus, erotic touching, manual stimulation, and fellatio were significantly less predictive; there were no differences between coitus and cunnilingus or coitus and kissing. Of the relationships (serious, dating, "friends with benefits" [FWBs], and "hookups"), FWBs was the strongest predictor of participants' desire, wanting, and pleasure; in comparison, hookups were significantly less predictive. These findings offer insight into the sexual behaviors and preferences of young women, as well as distinctions between types of non-romantic sexual relationships.

Progressive immune dysfunction and AIDS develop in most cases of human immunodeficiency virus type 1 (HIV-1) infection but in only 25 to 30% of persons with HIV-2 infection. However, the natural history and immunologic responses of individuals with dual HIV-1 and HIV-2 infection are largely undefined. Based on our previous findings, we hypothesized that among patients with dual infection the control of HIV-1 is associated with the ability to respond to HIV-2 Gag epitopes and to maintain HIV-specific CD4(+) T-cell responses. To test this, we compared the HIV-specific ex vivo IFN-gamma enzyme-linked immunospot (ELISPOT) assay responses of 19 dually infected individuals to those of persons infected with HIV-1 or HIV-2 only. Further, we assessed the functional profile of HIV Gag-specific CD4(+) and CD8(+) T cells from nine HIV dually infected patients by using a multicolor intracellular cytokine staining assay. As determined by ELISPOT assay, the magnitude and frequency of IFN-gamma-secreting T-cell responses to gene products of HIV-1 were higher than those to gene products of HIV-2 (2.64 versus 1.53 log(10) IFN-gamma spot-forming cells/10(6) cells [90% versus 63%, respectively].) Further, HIV-1 Env-, Gag-, and Nef- and HIV-2 Gag-specific responses were common; HIV-2 Nef-specific responses were rare. HIV-specific CD4(+) T helper responses were detected in nine of nine dually infected subjects, with the majority of these T cells producing gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and, to a lesser extent, interleukin-2. The HIV-1 plasma viral load was inversely correlated with HIV-2 Gag-specific IFN-gamma-/TNF-alpha-secreting CD4(+) and HIV-2 Gag-specific IFN-gamma-secreting CD8(+) T cells. In conclusion, the T-cell memory responses associated with containment of single HIV-1 and HIV-2 infection play a similar significant role in the immune control of dual HIV-1 and HIV-2 infection.

Diabetes among African American women is a pressing health concern, yet there are few evaluated culturally relevant prevention programs for this population. This article describes a case study of the Eat Well Live Well Nutrition Program, a community-based, culturally specific diabetes prevention nutrition program for African American women. The stages of change theory and principles from community organization guided the development of the program. Health education strategies, including participatory development and program delivery by peer educators, were applied to promote cultural relevance. Results indicated that overall participants (90%) believed the program to be culturally relevant and were very satisfied with the program (82%). Cultural relevancy was significantly associated with greater program satisfaction and changes in dietary patterns when controlling for the number of sessions attended. Conclusions suggest that participatory strategies can be effective in designing culturally specific prevention programs for African American women.

Family participation is a core system of care value that is supported by previous research in medical, child welfare, and mental health settings. However, many parents with children receiving out-of-home mental health treatment experience restrictions on contact. This cross-sectional study examines the experiences of families (N = 102) regarding parent-child contact in relation to examples of national accreditation standards. Results of the national survey found that most respondents (79.4%) reported restrictions on contact, including limits based on behavioral contingencies (65.7%) and point and level systems (52.5%).

Quantitative in vitro autoradiography has identified high density ACE and AT(1) receptor binding at sites of cardiac injury in the adult rat, implicating Ang II, generated de novo at these sites (tissue Ang II) in contributing to repair. This hypothesis remains to be tested. In the study reported here we used a time-dependent rat model of cardiac injury wherein plasma levels of renin and Ang II are chronically suppressed by means of continuous treatment with aldosterone (0.75 microg/h) and 1% dietary NaCl. To further address a role for tissue Ang II in tissue repair, we administered oral valsartan (10 mg/kg/day) in combination with aldosterone/NaCl. On days 20 and 30 of each regimen, hearts were examined. In coronal sections, we assessed transcription factor NFkappaB activation (RelA subunit), inflammatory-cell infiltration and appearance of myofibroblasts by immunohistochemistry; mRNA expression of several inflammatory (NFkappaB-related) and fibrogenic (type I collagen) mediators of repair, using quantitative in situ hybridization; and ACE binding density, detected with quantitative in vitro autoradiography. Blood pressure was measured with a tail cuff. Untreated age- and sex-matched rats served as controls. On day 20, we found no evidence of cardiac injury, inflammation, or repair with aldosterone/NaCl treatment, with or without valsartan. In contrast, on day 30 of aldosterone/NaCl treatment, inflammatory cells and alpha-SMA-positive myofibroblasts colocalized with high-density ACE binding and histochemical evidence of fibrillar collagen accumulation at sites of microscopic scarring and perivascular fibrosis of intramyocardial coronary arteries that appeared in both right and left ventricles. The activation of NFkappaB and the increased mRNA expression of ICAM-1, MCP-1, TNF-alpha, TGF-beta(1), PAI-1, and type I collagen were also observed at these sites. Expression of vascular cell adhesion molecule-1 was unchanged. Valsartan significantly reduced (P <.01) the expression of these mediators and attenuated the expression of MCP-1. It reduced microscopic evidence of tissue damage and the extent of fibrosis. Blood pressure was increased in aldosterone-treated rats on days 20 and 30; this increase was suppressed by valsartan. We thus show that in this rat model of long-term aldosterone/NaCl administration, in which circulating Ang II is suppressed, AT(1) receptor-mediated actions of tissue Ang II are involved in regulating the expression of mediators of repair at vascular and nonvascular sites of cardiac injury, thereby implicating autocrine/paracrine properties of tissue Ang II in inflammatory and healing responses.

This study assesses attitudes toward elderly nursing home clients as interviewed by 255 aides from three Black cultural groups: Afro-Americans; English-speaking Caribbeans; and Haitians. Results indicate that aides from all three groups had generally positive attitudes toward the elderly and the English-speaking Caribbean group expressed the most positive attitudes. Aides did express some negative attitudes toward the families of the elderly residents for not taking care of the elderly at home. Results were interpreted as reflecting the cultural norms of the three groups which included the infrequent placement of elderly persons in nursing homes. Findings indicated a need for inservice workshops in cultural diversity for aides who serve clients from different cultural groups. Social work curricula should prepare graduate social workers to conduct such experiences.

The Perceptions of the Elderly Scale (PES) was administered to a sample of 246 aides working in nursing homes in the New York Metropolitan Area. The aides represented three Black American cultural groups: African Americans, English-speaking Caribbean Blacks (including Jamaicans, Trinidadians, and Barbadians) and Haitians. Members of these groups make up the overwhelming majority of nursing home aides in New York City. The results indicated that aides from all three groups had generally favorable attitudes toward the elderly, but the English-speaking Caribbean groups expressed significantly more favorable attitudes than aides in either of the two other groups. The observed differences were attributed to the traditional role of the older individual within West Indian culture as disciplinarian and authority figure. Implications for in-service education are discussed.

Seeds of Phaseolus vulgaris L. ev. Nerina were hand-sown inside open-top chambers (OTCs) in which the plants were exposed to charcoal-filtered air (CF treatment), ambient air (NF), or ambient air with added 6, 12, 18, 25 or 30 nl 1 -1 of ozone (NF6, NF12, NF18, NF25 and NF30 treatments, respectively). Exposure commenced as the crop emerged and continued on a daily basis until the end of the season. Ozone (O 3 ) was added between 10.00 and 18.00 h GMT. The seasonal 7 h mean O 3 concentrations ranged from 10 nl l -1 in the CF treatment to 50 nl l -1 in the NF30 treatment. The growth and yield of P. vulgaris ev. Nerina demonstrated two distinct responses to O 3 depending upon concentration. At seasonal 7 h means of 20, 26 and 32 nl l -1 (NF, NF6 and NF12 treatments respectively), the yield increased relative to that of the CF treatment. The increase in yield peaked at 48% in the NF6 treatment (P < 0.05), and was associated with a 55 % increase in the maximum leaf number, longer retention of the canopy, and a 45 % increase in the number of pods present at the final harvest. In contrast, seasonal 7 h mean O 3 concentrations of 38, 45 and 50 nl l -1 (NF18, NF25 and NF30 treatments) caused 26-42 % reductions in the yield of P. vulgaris. The leaves of such plants developed extensive symptoms of O 3 injury and were prematurely abscised from the plants. The reductions in yield were due to a decrease in the numbers of seeds per pod and in the weights of individual seeds.

Limited proteolysis of catalytic and regulatory subunits of cyclic AMP-dependent protein kinase (A-pk), cyclic AMP phosphodiesterase, glycogen synthase, and histones by fungal protease (type XIX) was analyzed by the digested peptide bands in SDS polyacrylamide gel electrophoresis. The modulatory effects on proteolysis by nucleotides, polypeptides, and phospholipids may greatly depend on the intrinsic nature of substrates. The proteolysis of the regulatory subunit of A-pk and glycogen synthase was not regulated by nucleotides and nucleic acids. In comparison, phosphatidyl serine, cardiolipin, and pepstatin A stimulated the proteolysis of the catalytic subunit of A-pk. Whereas, lambda DNA (Hind III digest), t-RNA, GTP-, phosphatidyl serine, sphingosine inhibited the proteolysis of cyclic AMP phosphodiesterase. Moreover, MS2 RNA, lambda DNA, t-RNA, dGTP, Phosphatidyl serine, phosphatidyl inositol, antipain, and chymostatin exerted inhibitory proteolytic effect on histone VIII-S. Some of these agents also had similar inhibitory effect on other types of histones (types III-S and VII-S). The inhibitory effect of phosphatidyl serine on proteolysis of histone may be due to their interaction which was monitored by the drastic increase of uv absorbance.

Sephadex G-200 gel filtration of DNA cellulose-treated crude extracts of rat skeletal muscle, revealed a broad peak-fraction of tRNA-inhibitory protein kinases (PK) coeluted endogenous substrates. In comparison, the elution profile of baker's yeast exhibited multiple peak-fractions of tRNA-inhibiting PK. Various tRNA all showed inhibition to PK. In the presence of regulatory subunit of cyclic AMP-dependent protein kinase, tRNA did not exert synergetic inhibition on PK. Moreover, the interaction of tRNA with active muscle PK fractions could not be monitored by the increment of absorbance at 340 nm. tRNA had no significant regulatory effect on the phosphorylation of actin and myosin.

Various agents were tested for their effects on microbial proteases, which activity was monitored by the analysis of cleaved peptide bands in SDS-polyacrylamide gel electrophoresis. Using casein as a substrate, fungal protease (type XIX) was inhibited by the phenyl methyl sulphonyl fluoride, chymostatin, antipain and leupeptin, while bacterial protease (type XXVI) was inhibited by phosphatidyl glycerol, phosphatidyl inositol and sphingosine. MS2 RNA exerted minor inhibition on the bacterial proteolysis of regulatory subunits of cyclic AMP-dependent protein kinase (A-PK). The cleavage of DNA binding protein by both proteases was inhibited, in the presence of MS2 RNA and lambda DNA. In comparison, phosphatidyl serine slightly stimulated the fungal protease on the cleavage of ribonuclease T1. RNA polymerase is a good substrate of the bacterial protease as indicated by the generation of multiple cleaved peptide fragments, whereas alkaline phosphatase is not susceptible to proteolysis.

Two groups of patients admitted to psychiatric hospital in Dumfries were studied, drawn from the periods 1880-1889 and 1970-1979. Feighner criteria were applied to make three diagnostic categories - depression, mania and schizophrenia - and the occurrence and content of delusions were noted for each. A significant decline in the prevalence of delusional depressive illness was found between the two periods, and a similar trend was noted for delusional manic illness. In contrast, the prevalence of delusional schizophrenic illness was stable. This decline is taken to reflect a change in the phenomenology of affective illness since last century in South West Scotland. The content of delusions is also discussed.

The uptake of [3H]acetyl-labelled hyaluronic acid (HA) was examined in the liver, spleen and kidney of the rat after i.v. injection. 3H-activity was located by light- and electron-microscopic autoradiography after measurement by scintillation counting of tissue digests. In the liver, approximately 90% of the radioactivity was located in the sinusoidal endothelial cells, with autoradiographic grains distributed throughout the cytoplasm; 50% of the grains overlay vacuoles 0.3 to 1.2 micron in diameter. A few grains (4%) were located in Disse's space or nearby in the cytoplasm of hepatocytes. No grains were found in Kupffer cells. The remainder were randomly scattered across the sections in a pattern indicating nonspecific background activity. These observations are in accordance with the selective uptake of HA exhibited by dissociated liver cells in vitro. HA concentrations in the spleen and kidney were too low for detection by autoradiography. Splenic concentrations were much lower than in rabbits or mice; in this respect the uptake of circulating HA in the rat resembles that reported for chondroitin 4-sulphate.

Injury and poisoning episodes at the Regional Poisoning Treatment Centre, Edinburgh, were compared for the years 1980-1986. Injury was more likely to be associated with youth, male sex and single status. When these demographic differences were controlled for, injury was found to be associated with the following clinical variables: personality disorder, previous psychiatric inpatient status, use of alcohol at the time of parasuicide and alcohol problems, and the social variables-violence against others and received from relatives in the preceding 5 years, criminal record and unemployment. These have been consistently associated with repetition of parasuicide. A history of injury as a putative marker of repetition and the clinical implication of its association with alcohol problems are discussed.

The point-prevalence of tardive dyskinesia in schizophrenics from a discrete geographical area (Nithsdale, in Dumfries and Galloway Region) in 1981, 1982, and 1984 was 31%, 27%, and 30% respectively. This suggests that the prevalence of tardive dyskinesia in a community of schizophrenics has reached a plateau. In 12% of patients there was persistent dyskinesia, i.e. abnormal involuntary movements were present at all three assessments. Persistent dyskinesia was more common in older patients. The severity of tardive dyskinesia fluctuated between assessments in 41% of patients, indicating that it is only a transient feature in some cases.