Behavior, synaptic mitochondria, and microglia are differentially impacted by chronic adolescent stress and repeated endotoxin exposure in male and female rats.

Early life adversity and chronic inflammation have both been associated with cognitive impairment and neural compromise. In this study, we investigated the interactions between a history of chronic adolescent stress (CAS) and repeated endotoxin exposure on behavior, synaptic mitochondria, and microglia in adult male and female Wistar rats. Adult rats from chronic stress and control conditions were exposed to either repeated endotoxin (lipopolysaccharide; LPS) or saline injections every 3 days for 9 weeks. In both sexes, repeated LPS, regardless of stress history, impaired working memory in the Y maze. Regarding spatial memory, LPS impaired function for females; whereas, CAS altered function in males. Although males had an increase in anxiety-like behavior shortly after CAS, there were no long-term effects on anxiety-like behavior or social interaction observed in males or females. Stress did not alter synaptic mitochondrial function in either sex. Repeated LPS altered synaptic mitochondrial function such that ATP production was increased in females only. There were no observed increases in IBA-1 positive cells within the hippocampus for either sex. However, LPS and CAS altered microglia morphology in females. Impact of repeated LPS was evident at the terminal endpoint with increased spleen weight in both sexes and decreased adrenal weight in males only. Circulating cytokines were not impacted by repeated LPS at the terminal endpoint, but evidence of CAS effects on cytokines in females were evident. These data suggest a long-term impact of chronic stress and an impact of repeated endotoxin challenge in adulthood; however, not all physiological and behavioral metrics examined were impacted by the paradigm employed in this study and the two environmental challenges rarely interacted.

Chronic stress beginning in adolescence decreases spatial memory following an acute inflammatory challenge in adulthood.

Prolonged stress beginning in adolescence can contribute to the dysregulation of the neuroendocrine system in adulthood. As the neuroendocrine and neuroimmune systems participate in bi-directional regulatory control, adolescent stress can prime the neuroimmune system to future inflammatory insults. Previous work from our group demonstrates that stress exaggerates the hippocampal response to inflammation, which can lead to deficits in learning and memory. In the current study, we sought to interrogate the interaction between an acute peripheral challenge of lipopolysaccharide (LPS) in male and female Wistar rats with a history of stress beginning in adolescence (CAS). Males from the CAS group were more vulnerable to the peripheral effects of LPS compared to non-stressed males including porphyrin staining and ruffled fur. In contrast, LPS generated similar peripheral effects in females regardless of adolescent stress history. Learning and memory were differentially impacted by LPS as a function of stress history and effects manifested differently when stratified by sex. Males with a history of adolescent stress exhibited deficits in initial learning. Females from the CAS group performed similar to controls during acquisition but exhibited a slight impairment during reversal learning. Males and females with a history of stress displayed memory impairment during the probe assessments as compared to their same-sex control group. We conclude that while stress beginning in adolescence enhanced the vulnerability of learning and memory to an inflammatory challenge, the phenotype of this effect manifested differently in males and females. These data demonstrate a sustained impact of adolescent stress on the neuroimmune system which is sufficient to influence cognitive performance in both sexes.

Chronic adolescent stress causes sustained impairment of cognitive flexibility and hippocampal synaptic strength in female rats.

Females that experience chronic stress during development, particularly adolescence, are the most vulnerable group to stress-induced disease. While considerable attention has been devoted to stress-induced manifestation of anxiety, depression, and PTSD, evidence indicates that a history of chronic stress is also a risk factor for cognitive decline and dementia - with females again in a higher risk group. This interplay between sex and stress history indicates specific mechanisms drive neural dysfunction across the lifespan. The presence of sex and stress steroid receptors in the hippocampus provides a point of influence for these variables to drive changes in cognitive function. Here, we used a rodent model of chronic adolescent stress (CAS) to determine the extent to which CAS modifies glutamatergic signaling resulting in cognitive dysfunction. Male and female Wistar rats born in-house remained non-stressed (NS), unmanipulated aside from standard cage cleaning, or were exposed to either physical restraint (60 min) or social defeat (CAS) each day (6 trials each), along with social isolation, throughout the adolescent period (PND 35-47). Cognition was assessed in adult (PND 80-130) male and female rats (n = 10-12) using the Barnes Maze task and the Attention Set-Shift task. Whole hippocampi were extracted from a second cohort of male and female rats (NS and CAS; n = 9-10) and processed for RNA sequencing. Brain tissue from the first cohort (n = 6) was processed for density of glutamatergic synaptic markers (GluA1, NMDA1a, and synaptophysin) or whole-cell patch clamping (n = 4) to determine glutamatergic activity in the hippocampus. Females with a history of chronic stress had shorter latencies to locate the goal box than NS controls during acquisition learning but showed an increased latency to locate the new goal box during reversal learning. This reversal deficit persisted across domains as females with a history of stress required more trials to reach criterion during the reversal phases of the Attention Set-Shift task compared to controls. Ovariectomy resulted in greater performance variability overall during reversal learning with CAS females showing worse performance. Males showed no effects of CAS history on learning or memory performance. Bioinformatic prediction using gene ontology categorization indicated that in females, postsynaptic membrane gene clusters, specifically genes related to glutamatergic synapse remodeling, were enriched with a history of stress. Structural analysis indicated that CAS did not alter glutamate receptor density in females. However, functionally, CAS females had a decreased AMPA/NMDA-dependent current ratio compared to controls indicating a weakening in synaptic strength in the hippocampus. Males showed only a slight change in density of NMDA1a labeling in the CA3 region with a history of stress. The data observed here suggest that females are at risk for impaired cognitive flexibility following a history of adolescent stress, possibly driven by changes in glutamatergic signaling.

The mechanics of setting up a COVID-19 response: Experiences of the COVID-19 epidemic from Groote Schuur Hospital, Cape Town, South Africa.

The SARS-CoV-2 pandemic has challenged the provision of healthcare in ways that are unprecedented in our lifetime. Planning for the sheer numbers expected during the surge has required public hospitals to de-escalate all non-essential clinical services to focus on COVID-19. Western Cape Province was the initial epicentre of the COVID-19 epidemic in South Africa (SA), and the Cape Town metro was its hardest-hit geographical region. We describe how we constructed our COVID-19 hospital-wide clinical service at Groote Schuur Hospital, the University of Cape Town's tertiary-level teaching hospital. By describing the barriers and enablers, we hope to provide guidance rather than a blueprint for hospitals elsewhere in SA and in low-resource countries that face similar challenges now or during subsequent waves.

Costs of potentially inappropriate medication use in residential aged care facilities.

BACKGROUND: The potential harms of some medications may outweigh their potential benefits (inappropriate medication use). Despite recommendations to avoid the use of potentially inappropriate medications (PIMs) in older adults, the prevalence of PIM use is high in different settings including residential aged care. However, it remains unclear what the costs of these medications are in this setting. The main objective of this study was to determine the costs of PIMs in older adults living in residential care. A secondary objective was to examine if there was a difference in costs of PIMs in a home-like model of residential care compared to an Australian standard model of care. METHODS: Participants included 541 participants from the Investigation Services Provided in the Residential Environment for Dementia (INSPIRED) Study. The INSPIRED study is a cross-sectional study of 17 residential aged care facilities in Australia. 12 month medication costs were determined for the participants and PIMs were identified using the 2015 updated Beers Criteria for older adults. RESULTS: Of all of the medications dispensed in 1 year, 15.9% were PIMs and 81.4% of the participants had been exposed to a PIM. Log-linear models showed exposure to a PIM was associated with higher total medication costs (Adjusted ß = 0.307, 95% CI 0.235 to 0.379, p < 0.001). The mean proportion (±SD) of medication costs that were spent on PIMs in 1 year was 17.5% (±17.8) (AUD$410.89 ± 479.45 per participant exposed to a PIM). The largest PIM costs arose from proton-pump inhibitors (34.4%), antipsychotics (21.0%) and benzodiazepines (18.7%). The odds of incurring costs from PIMs were 52% lower for those residing in a home-like model of care compared to a standard model of care. CONCLUSIONS: The use of PIMs for older adults in residential care facilities is high and these medications represent a substantial cost which has the potential to be lowered. Further research should investigate whether medication reviews in this population could lead to potential cost savings and improvement in clinical outcomes. Adopting a home-like model of residential care may be associated with reduced prevalence and costs of PIMs.

International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010.

STUDY QUESTION: What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010? SUMMARY ANSWER: Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates. WHAT IS KNOWN ALREADY: ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010. PARTICIPANTS, SETTING, METHODS: Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level. MAIN RESULTS AND THE ROLE OF CHANCE: For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010. LIMITATIONS, REASON FOR CAUTION: The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity. WIDER IMPLICATIONS OF FINDINGS: The ICMART World Reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment and embryo transfer practices warrant attention by clinicians and policy makers. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Reproductive Technology; Government of Canada (Research grant), Ferring Pharmaceuticals (Grant unrelated to World Reports). TRIAL REGISTRATION: not applicable.

High-efficiency superconducting nanowire single-photon detectors fabricated from MoSi thin-films.

We report on MoSi SNSPDs which achieved high system detection efficiency (87.1 ± 0.5% at 1542 nm) at 0.7 K and we demonstrate that these detectors can also be operated with saturated internal efficiency at a temperature of 2.3 K in a Gifford-McMahon cryocooler. We measured a minimum system jitter of 76 ps, maximum count rate approaching 10 MHz, and polarization dependence as low as 3.3 ± 0.1%. The performance of MoSi SNSPDs at 2.3 K is similar to the performance of WSi SNSPDs at < 1 K. The higher operating temperature of MoSi SNSPDs makes these devices promising for widespread use due to the simpler and less expensive cryogenics required for their operation.

Factors influencing the pharmacological management of osteoporosis after fragility fracture: results from the Ontario Osteoporosis Strategy's fracture clinic screening program.

UNLABELLED: Potential mediating factors in the pathway to initiation of osteoporosis treatment following a fragility fracture were evaluated. Patients' perceived need for treatment, mediated by their perception of bone density test results, was central to treatment initiation. Interventions focusing on patients' perceptions of need and test results may improve treatment rates. INTRODUCTION: We tested a hypothesized pathway to osteoporosis (OP) pharmacotherapy initiation in fragility fracture patients. We hypothesized that bone mineral density (BMD) testing is strongly associated with treatment initiation and perception of BMD test results would inform patients' perceived need for treatment, which would mediate the effect between BMD testing and treatment initiation. METHODS: A longitudinal cohort study followed patients, ≥50 years of age, screened for fragility fracture in 31 fracture clinics in Ontario, Canada who had no prior diagnosis of or treatment for OP. At screening, OP risk factors, baseline-patient perception of OP risk, OP knowledge, and perceived benefits of medication were reported by patients. Patients were followed up within 6 months of fracture to determine BMD testing and prescription of and adherence to first-line OP pharmacotherapy. Structural equation modeling tested the hypothesized pathway. Significance and magnitude of the coefficients and indicators of overall model fit were used to test our model. RESULTS: The direct path from BMD testing to OP treatment initiation was non-significant. The pathway to treatment initiation was mediated by patients' perception of their need, which was influenced by their self-reported BMD results. Baseline fracture risk factors, knowledge of OP, and perceived benefits of treatment-predicted patient-perceived need for treatment at follow-up and initiation of OP treatment. CONCLUSIONS: Patient perceptions were central factors in the path to initiation of OP pharmacotherapy. Interventions to facilitate accurate patient perceptions of BMD test results and OP risk status could prove helpful in improving OP treatment initiation.

Acute sphenoid sinusitis leading to contralateral cavernous sinus thrombosis: a case report.

INTRODUCTION: The objective of this article was to report a case of isolated, acute, right-sided sphenoid sinusitis that progressed to contralateral cavernous sinus thrombosis in an 18-year-old male patient. We describe the atypical presentation of this case and discuss the relevant anatomy, pathogenesis, presentation, diagnostic evaluation and treatment. CASE REPORT: A case report of sphenoid sinusitis leading to contralateral cavernous sinus thrombosis was reviewed and presented along with a comprehensive literature review of the relevant anatomy, pathophysiology, microbiology, diagnostic work-up and treatment options. CONCLUSION: Cavernous sinus thrombosis is a rare clinical entity in the antibiotic era. However, limited sphenoid sinusitis may progress to cavernous sinus thrombosis in spite of maximal medical treatment, as highlighted in this case report. The mainstay of treatment includes early diagnosis allowing aggressive intravenous antibiotics and appropriate surgical management.

Derivation of freshwater quality criteria for zinc using interspecies correlation estimation models to protect aquatic life in China.

Species sensitivity distributions (SSDs) are usually used in the development of water quality criteria and require a large number of toxicity values to define a hazard level to protect the majority of species. However, some toxicity data for certain chemicals are limited, especially for endangered and threatened species. Thus, it is important to predict the unknown species toxicity data using available toxicity data. To address this need, interspecies correlation estimation (ICE) models were developed by US EPA to predict acute toxicity of chemicals to diverse species based on a more limited data set of surrogate species toxicity data. Use of SSDs generated from ICE models allows for the prediction of protective water quality criteria, such as the HC5 (hazard concentration, 5th percentile). In the present study, we tested this concept using toxicity data collected for zinc. ICE-based-SSDs were generated using three surrogate species (common carp (Cyprinus carpio), rainbow trout (Oncorhynchus mykiss), and Daphnia magna) and compared with the measured-based SSD and corresponding HC5. The results showed that no significant differences were observed between the ICE- and the measured-based SSDs and HC5s. Furthermore, the examination of species placements within the SSDs indicated that the most sensitive species to zinc were invertebrates, especially crustaceans. Given the similarity of SSD and HC5s for zinc, the use of ICE to derive potential water quality criteria for diverse chemicals in China is proposed. Further, a combination of measured and ICE-derived data will prove useful for assessing water quality and chemical risks in the near future.

The economic impact of infertility on women in developing countries ­ a systematic review.

BACKGROUND: It is the responsibility of health systems to provide quality health care and to protect consumers against impoverishing health costs. In the case of infertility in developing countries, quality care is often lacking and treatment costs are usually covered by patients. Additional financial hardship may be caused by various social consequences. The economic implications of infertility and its treatment have not been systematically explored. METHODS: A systematic MEDLINE search was conducted to identify English language publications providing original data from developing countries on out-of-pocket payment (OoPP) for infertility treatment and on other economic consequences of involuntary childlessness. FINDINGS: Twenty one publications were included in this review. Information on OoPP was scant but suggests that infertility treatment is associated with a significant risk of catastrophic expenditure, even for basic or ineffective interventions. Other economic disadvantages, which may be profound, are caused by loss of access to child labour and support, divorce, as well as customary laws or negative attitudes which discriminate against infertile individuals. Women in particular are affected. CONCLUSION: Pertinent data on OoPP and other economic disadvantages of infertility in developing countries are limited. According to the evidence available, infertility may cause impoverishing health costs as well as economic instability or deprivation secondary to social consequences. Health systems in developing countries do not appear to meet their responsibilities vis-à-vis infertile patients.

SU-E-I-86: Image Fusion Verification Using a Vendor-Independent Phantom.

PURPOSE: To evaluate the image fusion accuracy of a hybrid PET/CT or SPECT/CT system using a recently developed vendor-independent phantom. METHODS: The basic design of the fusion verification phantom is a 10 cm urethane cube with three 1 mm diameter channels each fitted with standard Luer connection designed to be filled with a radioactive solution. The channels also have a 0.4 mm diameter steel wire inserted in each channel. There are two versions of this cube phantom with different orientations of the wire/liquid filled channels. There is the perpendicular cube with three channels each parallel to the x, y and z axes. The second cube orientation has two opposing angled channels and one that is perpendicular to the cube base. When imaged with either a PET/CT or SPECT/CT device the wire yields a high contrast image against a high signal target of the radioisotope filled channel. Both phantoms are scanned on various vendor and model hybrid systems. RESULTS: Three plane reconstructed data of the perpendicular fusion phantom generates images with point source like targets of the emission and transmission data for quick visual evaluation of registration accuracy for x, y and z shifts. A series of axial reconstructed images can be used to evaluate alignment when using the opposing ramp fusion phantom. The unique utility of the opposing ramps allows for verification of a z-axis offset from the single axial image data. Alignment data are presented from a number of PET/CT and SPECT/CT systems. CONCLUSIONS: The use of either the perpendicular or opposing ramp fusion phantom provides a convenient QC vendor independent tool for evaluation of image alignment accuracy of hybrid imaging systems. The design supports a simple 3D processing with a straightforward visual interpretation of alignment.

The use of 137Cs to establish longer-term soil erosion rates on footpaths in the UK.

There is increasing awareness of the damage caused to valuable and often unique sensitive habitats by people pressure as degradation causes a loss of plant species, disturbance to wildlife, on-site and off-site impacts of soil movement and loss, and visual destruction of pristine environments. This research developed a new perspective on the problem of recreational induced environmental degradation by assessing the physical aspects of soil erosion using the fallout radionuclide caesium-137 ((137)Cs). Temporal sampling problems have not successfully been overcome by traditional research methods monitoring footpath erosion and, to date, the (137)Cs technique has not been used to estimate longer-term soil erosion in regard to sensitive recreational habitats. The research was based on-sites within Dartmoor National Park (DNP) and the South West Coast Path (SWCP) in south-west England. (137)Cs inventories were reduced on the paths relative to the reference inventory (control), indicating loss of soil from the path areas. The Profile Distribution Model estimated longer-term erosion rates (ca. 40 years) based on the (137)Cs data and showed that the combined mean soil loss for all the sites on 'paths' was 1.41 kg m(-2) yr(-1) whereas the combined 'off path' soil loss was 0.79 kg m(-2) yr(-1), where natural (non-recreational) soil redistribution processes occur. Recreational pressure was shown to increase erosion in the long-term, as greater soil erosion occurred on the paths, especially where there was higher visitor pressure.

Use of watershed factors to predict consumer surfactant risk, water quality, and habitat quality in the upper Trinity River, Texas.

Surfactants are high production volume chemicals that are used in a wide assortment of "down-the-drain" consumer products. Wastewater treatment plants (WWTPs) generally remove 85 to more than 99% of all surfactants from influents, but residual concentrations are discharged into receiving waters via wastewater treatment plant effluents. The Trinity River that flows through the Dallas-Fort Worth metropolitan area, Texas, is an ideal study site for surfactants due to the high ratio of wastewater treatment plant effluent to river flow (>95%) during late summer months, providing an interesting scenario for surfactant loading into the environment. The objective of this project was to determine whether surfactant concentrations, expressed as toxic units, in-stream water quality, and aquatic habitat in the upper Trinity River could be predicted based on easily accessible watershed characteristics. Surface water and pore water samples were collected in late summer 2005 at 11 sites on the Trinity River in and around the Dallas-Fort Worth metropolitan area. Effluents of 4 major waste water treatment plants that discharge effluents into the Trinity River were also sampled. General chemistries and individual surfactant concentrations were determined, and total surfactant toxic units were calculated. GIS models of geospatial, anthropogenic factors (e.g., population density) and natural factors (e.g., soil organic matter) were collected and analyzed according to subwatersheds. Multiple regression analyses using the stepwise maximum R(2) improvement method were performed to develop prediction models of surfactant risk, water quality, and aquatic habitat (dependent variables) using the geospatial parameters (independent variables) that characterized the upper Trinity River watershed. We show that GIS modeling has the potential to be a reliable and inexpensive method of predicting water and habitat quality in the upper Trinity River watershed and perhaps other highly urbanized watersheds in semi-arid regions.

Environmental properties of long-chain alcohols. Part 2: Structure-activity relationship for chronic aquatic toxicity of long-chain alcohols.

Daphnia magna reproduction tests were performed with C(10), C(12), C(14) and C(15) alcohols to establish a structure-activity relationship of chronic effects of long-chain alcohols. The data generation involved substantial methodological efforts due to the exceptionally rapid biodegradability of the test substances and the need to test as close as possible to their water solubility limits. Test concentrations were determined by GC-MS before and after test solution renewal. Whereas apparent toxicity based on survival and reproduction increased with increasing C-chain lengths up to C(14), observations of toxicity to C(15) alcohol were not in line with lower chain lengths due to the lack of toxicity below the level of water solubility. When omitting C(15), the slope of most (Q)SARs approach -1, being consistent with the expectation of a non-polar narcotic mode of action. Further testing at higher chain lengths is not sensible due to progressively lower solubility, at remaining biodegradability. Effects on mortality and reproduction are not expected below the level of water solubility.

Assessment of the environmental risk of long-chain aliphatic alcohols.

An environmental assessment of long-chain alcohols (LCOH) has recently been conducted under the OECD SIDS High Production Volume (HPV) Program via the Global International Council of Chemical Associations (ICCA) Aliphatic Alcohols Consortium. LCOH are used primarily as intermediates, as a precursor to alcohol-based surfactants and as alcohol per se in a wide variety of consumer product applications. Global production volume is approximately 1.58 million metric tonnes. The OECD HPV assessment covers linear to slightly branched LCOH ranging from 6 to 22 alkyl carbons (C). LCOH biodegrade exceptionally rapidly in the environment (half-lives on the order of minutes); however, due to continuous use and distribution to wastewater treatment systems, partitioning properties, biodegradation of alcohol-based surfactants, and natural alcohol sources, LCOH are universally detected in wastewater effluents. An environmental risk assessment of LCOH is presented here by focusing on the most prevalent and toxic members of the linear alcohols, specifically, from C(12-15). The assessment includes environmental monitoring data for these chain lengths in final effluents of representative wastewater treatment plants and covers all uses of alcohol (i.e., the use of alcohol as a substance and as an intermediate for the manufacturing of alcohol-based surfactants). The 90th percentile effluent discharge concentration of 1.979microg/L (C(12)-C(15)) was determined for wastewater treatment plants in 7 countries. Chronic aquatic toxicity studies with Daphnia magna demonstrated that between C(13) and C(15) LCOH solubility became a factor and that the structure-activity relationship was characterized by a toxicity maximum between C(13) and C(14). Above C(14) the LCOH was less toxic and become un-testable due to insolubility. Risk quotients based on a toxic units (TU) approach were determined for various scenarios of exposure and effects extrapolation. The global average TU ranged from 0.048 to 0.467 depending on the scenario employed suggesting a low risk to the environment. The fact that environmental exposure calculations include large fractions of naturally derived alcohol from animal, plant, and microbially mediated biotransformations further supports a conclusion of low risk.

Ensembl 2008.

The Ensembl project (http://www.ensembl.org) is a comprehensive genome information system featuring an integrated set of genome annotation, databases and other information for chordate and selected model organism and disease vector genomes. As of release 47 (October 2007), Ensembl fully supports 35 species, with preliminary support for six additional species. New species in the past year include platypus and horse. Major additions and improvements to Ensembl since our previous report include extensive support for functional genomics data in the form of a specialized functional genomics database, genome-wide maps of protein-DNA interactions and the Ensembl regulatory build; support for customization of the Ensembl web interface through the addition of user accounts and user groups; and increased support for genome resequencing. We have also introduced new comparative genomics-based data mining options and report on the continued development of our software infrastructure.

Knowledge and expectations of labour among primigravid women in the public health sector.

OBJECTIVES: We analysed knowledge and expectations of the process and pain of labour in primigravidas attending a local midwifery obstetric unit (MOU). It was anticipated that the results of this study could inform the development of interventions aimed at improving the analgesic care of women delivering at primary health care obstetric units. DESIGN: Qualitative analysis of data obtained from in-depth semi-structured interviews. SETTING: A Cape Town MOU. SUBJECTS: 30 black African, Xhosa-speaking primigravidas. OUTCOME MEASURES: An open-ended interview guide was developed. The themes explored included previous painful experiences, knowledge of labour, expectations of and attitudes towards labour pain, and knowledge of biomedical analgesia. RESULTS: Patients were poorly informed about the process and pain of labour. Most women appeared highly motivated concerning their ability to cope with labour. Most expected pain, but had no concept of the severity or duration of the pain, and knew very little concerning methods available for pain relief in labour. CONCLUSION: Women at this MOU were poorly prepared for the experience of delivery. Antenatal programmes should incorporate sensitive education concerning the process and pain of labour and the methods available to alleviate pain.

Readers should systematically assess methods used to identify, measure and analyze confounding in observational cohort studies.

OBJECTIVE: To describe techniques used to address confounding in published observational studies. STUDY DESIGN AND SETTING: A systematic literature review identified studies using administrative or registry data to investigate health effects of drug therapies. Studies published from January 2001 to December 2005 came from BMJ, New England Journal of Medicine, Lancet, Annals of Internal Medicine, and JAMA. A structured abstraction form was used to collect information about confounding. RESULTS: The search identified 29 studies. Twenty-two studies (76%) had 10,000 or more subjects and 18 (62%) used a mortality outcome. None mentioned use of a literature search to identify confounders, however, 28 (97%) listed confounders included, and 26 (90%) listed confounders not included in the study. Eighteen (62.1%) discussed the validity of confounder data. Most (22, or 76%) studies included a table with the distribution of confounders but none used effect size to assess imbalance between comparison groups. Almost all studies used regression techniques (28, or 97%); fewer used stratification (16, or 55%) or matching (four, or 14%) to address confounding. Eleven (40%) studies discussed sensitivity analyses. CONCLUSION: Published cohort studies routinely include a list of potential confounders but there is room for improvement in confounder identification, measurement, and analysis.