Biocompatibility of Antifogging SiO-doped Diamond-Like Carbon Laparoscope Coatings.

Laparoscopes can suffer from fogging and contamination difficulties, resulting in a reduced field of view during surgery. A series of diamond-like carbon films, doped with SiO, were produced by pulsed laser deposition for evaluation as biocompatible, antifogging coatings. DLC films doped with SiO demonstrated hydrophilic properties with water contact angles under 40°. Samples subjected to plasma cleaning had improved contact angle results, with values under 5°. Doping the DLC films with SiO led to an average 40% decrease in modulus and 60% decrease in hardness. Hardness of the doped films, 12.0 - 13.2 GPa, was greater than that of the uncoated fused silica substrate, 9.2 GPa. The biocompatibility was assessed through CellTiter-Glo assays, with the films demonstrating statistically similar levels of cell viability when compared to the control media. The absence of ATP released by blood platelets in contact with the DLC coatings suggests in vivo hemocompatibility. The SiO doped films displayed improved transparency levels in comparison to undoped films, achieving up to an average of 80% transmission over the visible spectrum and an attenuation coefficient of 1.1 × 104 cm-1 at the 450 nm wavelength. The SiO doped DLC films show promise as a method of fog prevention for laparoscopes.

Voluntary sustainability standards could significantly reduce detrimental impacts of global agriculture.

Voluntary sustainability standards (VSS) are stakeholder-derived principles with measurable and enforceable criteria to promote sustainable production outcomes. While institutional commitments to use VSS to meet sustainable procurement policies have grown rapidly over the past decade, we still have relatively little understanding of the (i) direct environmental benefits of large-scale VSS adoption; (ii) potential perverse indirect impacts of adoption; and (iii) implementation pathways. Here, we illustrate and address these knowledge gaps using an ecosystem service modeling and scenario analysis of Bonsucro, the leading VSS for sugarcane. We find that global compliance with the Bonsucro environmental standards would reduce current sugarcane production area (-24%), net tonnage (-11%), irrigation water use (-65%), nutrient loading (-34%), and greenhouse gas emissions from cultivation (-51%). Under a scenario of doubled global sugarcane production, Bonsucro adoption would further limit water use and greenhouse gas emissions by preventing sugarcane expansion into water-stressed and high-carbon stock ecosystems. This outcome was achieved via expansion largely on existing agricultural lands. However, displacement of other crops could drive detrimental impacts from indirect land use. We find that over half of the potential direct environmental benefits of Bonsucro standards under the doubling scenario could be achieved by targeting adoption in just 10% of global sugarcane production areas. However, designing policy that generates the most environmentally beneficial Bonsucro adoption pathway requires a better understanding of the economic and social costs of VSS adoption. Finally, we suggest research directions to advance sustainable consumption and production.

Comparing steam-flaked and pelleted barley grain in a feed-first guided-flow automated milking system for Holstein cows.

Provision of a palatable feed in automated milking systems (AMS) is considered an essential motivating factor to encourage voluntary visits to the milking stall. Although the quantity and composition of AMS concentrates have been previously investigated, the form of the concentrate has not been extensively evaluated. The objective of this study was to evaluate the effects of feeding pelleted (PB; 132.9 ± 56 DIM, 47.4 ± 9.51 kg/d milk yield) versus steam-flaked barley (SFB; 133.0 ± 63 DIM, 40.5 ± 8.23 kg/d milk yield) in an AMS on dry matter intake, AMS visits, milk and milk component yield, and partial mixed ration (PMR) feeding behavior. Twenty-nine Holstein cows of varying parities were enrolled in this study. Cows were housed in freestall housing with a feed-first guided-flow barn design; 7 cows were housed in a separate freestall pen to enable individual PMR intake and feeding behavior monitoring. This study was conducted as a 2-way crossover, with two 21-d periods in which each cow received the same basal PMR but was offered 2 kg/d (dry matter basis) of PB or SFB in the AMS. Cows receiving the SFB had fewer voluntary AMS visits (2.71 vs. 2.90 ± 0.051, no./d), tended to have a longer interval between milkings (541.7 vs. 505.8 ± 21.02 min), spent more time in the holding pen before entering the AMS (139.9 vs. 81.2 ± 11.68 min/d), and had lower total box time (19.7 vs. 21.4 ± 0.35 min/d) than cows fed PB. Despite changes in AMS attendance, there were no differences for average milk (44.0 kg/d), fat (1.62 kg/d), and protein (1.47 kg/d) yields or AMS concentrate intake (2.02 kg/d). These behavioral changes indicate that offering SFB as an alternative to PB may reduce motivation for cows to voluntarily enter the AMS.

Adherence to osteoporosis therapy after an upper extremity fracture: a pre-specified substudy of the C-STOP randomized controlled trial.

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor. INTRODUCTION: To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture. METHODS: Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients. RESULTS: By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not. CONCLUSION: While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01401556.

Cost-effectiveness of first-trimester screening with early preventative use of aspirin in women at high risk of early-onset pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11-13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada. METHODS: A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (< 16 weeks) use of low-dose aspirin in those at high risk was simulated and compared with current practice using decision-tree analysis. The probabilities at each decision point and associated costs of utilized resources were calculated based on published literature and public databases. RESULTS: Of the theoretical 387 516 births per year, the estimated prevalence of early PE based on first-trimester screening and aspirin use was 705 vs 1801 cases based on the current practice. This was associated with an estimated total cost of C$9.52 million with the first-trimester screening program compared with C$23.91 million with current practice for the diagnosis and management of women with early-onset PE. This equals an annual cost saving to the Canadian healthcare system of approximately C$14.39 million. CONCLUSIONS: The implementation of a first-trimester screening program for PE and early intervention with aspirin in women identified as high risk for early PE has the potential to prevent a significant number of early-onset PE cases with a substantial associated cost saving to the healthcare system in Canada. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes.

We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a ß-blocker-based strategy (ß-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis P=5.3 × 10-8). rs11124945 G allele carriers had lower odds for NOD when exposed to the ß-blocker strategy compared with the CCB strategy (Odds ratio OR=0.38(0.24-0.60), P=4.0 × 10-5), whereas A/A homozygotes exposed to the ß-blocker strategy had increased odds for NOD compared with the CCB strategy (OR=2.02(1.39-2.92), P=2.0 × 10-4). eQTL annotation of the 2p21 locus provides functional support for regulating gene expression.

History of mood or anxiety disorders and risk of gestational diabetes mellitus in a population-based cohort.

AIM: To examine the association between mood and anxiety disorders and the development of gestational diabetes mellitus in a retrospective population-based cohort study. METHODS: Clinical data from a provincial perinatal health registry were linked to physician claims, hospitalization records and emergency visits to identify any diagnoses of mood or anxiety disorders in the 2 years prior to pregnancy and a subsequent diagnosis of gestational diabetes during pregnancy. The study population included all singleton pregnancies in the Canadian province of Alberta from 1 April 2000 to 31 March 2010. Generalized estimating equations were used to determine the adjusted odds ratio of gestational diabetes, comparing women with and without a history of mood or anxiety disorders. RESULTS: Among 373 674 pregnancies from 253 911 women, 25.7% had a history of mood or anxiety disorders, and 3.8% developed gestational diabetes. The multivariate-adjusted odds of developing gestational diabetes were higher among women with a history of mood or anxiety disorders (odds ratio 1.10, 95% CI 1.06-1.14). CONCLUSIONS: Women with a history of mood or anxiety disorders had a moderately increased risk of developing gestational diabetes.

Risk of prostate cancer across different racial/ethnic groups in men with diabetes: a retrospective cohort study.

AIM: To examine the associations between prostate cancer, diabetes and race/ethnicity. METHODS: Using administrative data from British Columbia, Canada for the period 1994 to 2012, we identified men aged ≥50 years with and without diabetes. Validated surname algorithms identified men as Chinese, Indian or of other race/ethnicity. Multivariable Cox regression was used to estimate adjusted risks of prostate cancer according to diabetes status and race/ethnicity. RESULTS: Our cohort of 160 566 men had a mean (sd) age of 64.7 (9.4) years and a median of 9 years' follow-up. The incidence rates of prostate cancer among those with and without diabetes were 177.4 (171.7-183.4) and 216.0 (209.7-222.5) per 1000 person-years, respectively. The incidence among Chinese men was 120.9 (109.2-133.1), among Indian men it was 144.1 (122.8-169.0) and in men of other ethnicity it was 204.8 (200.2-209.5). Diabetes was independently associated with a lower risk of prostate cancer (adjusted hazard ratio 0.82, 95% CI 0.78-0.86), as was Chinese (adjusted hazard ratio 0.54, 95% CI 0.46,0.63) and Indian (adjusted hazard ratio 0.66, 95% CI 0.49,0.89) race/ethnicity; however, there was no statistically significant interaction between diabetes status and race/ethnicity (all P>0.1). CONCLUSION: Diabetes and Chinese and Indian race/ethnicity were each independently associated with a lower risk of prostate cancer.

Transverse technique: complementary approach to measurement of first-trimester uterine artery Doppler.

OBJECTIVES: To define a protocol for the first-trimester assessment of uterine artery pulsatility index (UtA-PI) using the new transverse technique, to evaluate UtA-PI measured using the transverse approach vs that obtained using the conventional sagittal approach and to determine if accelerated onsite training (in both methods) of inexperienced sonographers can achieve reproducible UtA-PI measurements comparable with those obtained by an experienced sonographer. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for routine combined first-trimester screening at 11 to 13 + 6 weeks' gestation. The study consisted of two parts, each conducted at a different center (Part 1 in Calgary, Canada and Part 2 in Hong Kong). In Part 1, UtA-PI measurements were performed using the transverse and sagittal techniques by four sonographers trained in both methods, in 10 cases each, and measurement indices (PI), time required and subjective difficulty in obtaining satisfactory measurements were compared. The one sample t-test and Wilcoxon signed rank test were used when appropriate. Bland-Altman plots were used to assess measurement agreement, and intraclass correlation coefficient (ICC) was used to evaluate measurement reliability. A target plot was used to assess measures of central tendency and dispersion. In Part 2, one experienced and three inexperienced sonographers prospectively measured UtA-PI using both approaches in 42 and 35 women, respectively. Inexperienced sonographers underwent accelerated onsite training by the experienced sonographer. Measurement approach and sonographer order were on a random basis. ICC, Bland-Altman and Passing-Bablok analyses were performed to assess measurement agreement and reliability and effect of accelerated training. RESULTS: In Part 1, no difference was observed between the two techniques in mean time to acquire the measurements (118 s for sagittal vs 106 s for transverse; P = 0.38). The four sonographers reported that the transverse technique was subjectively easier to perform (P = 0.04). Bias and ICC for mean UtA-PI between sagittal and transverse measurements were -0.05 (95% limits of agreement, -0.48 to 0.37) and 0.94, respectively. Measurements obtained using the transverse technique after correcting for gestational age were significantly closer to the expected distribution than those obtained using the sagittal technique. In Part 2, there were no significant differences in median UtA-PI measured using the different approaches for both experienced and inexperienced sonographers (P > 0.05 for all sonographers). Mean UtA-PI measurement reliability between approaches was high for the experienced (ICC = 0.92) and inexperienced (ICC > 0.80) sonographers. UtA-PI measurement approaches did not deviate from linearity, while bias ranged from -0.10 to 0.07. The median time required was similar between the techniques (56.1 s for sagittal vs 49.3 s for transverse; P = 0.054). CONCLUSIONS: This novel transverse approach for the measurement of UtA-PI in the first trimester appears to be comparable with the sagittal approach in terms of reliability, reproducibility and time required, and may be easier to perform. Providing accelerated onsite training can be helpful for improving the reliability of UtA-PI measurements and could potentially facilitate the broad implementation of first-trimester pre-eclampsia screening. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Effects of substance use screening and brief intervention on health-related quality of life.

PURPOSE: Screening, brief intervention, and referral to treatment interventions have been shown to positively impact alcohol use. These programs utilize motivational interviewing techniques in an effort to reduce risky substance use among those at elevated risk of developing a disorder. However, there is a dearth of research assessing positive impacts above and beyond changes in alcohol use. This study examines potential benefits of brief interventions, utilizing motivation interviewing, on mental and physical quality of life. METHODS: The present quasi-experimental study examined changes in health-related quality of life among individuals presenting at urban emergency departments. The analyses included the use of propensity score matching to minimize potential biases resulting from differences between groups at baseline. RESULTS: The results indicated that the intervention group experienced significant increases in perceptions of mental health over those of the comparison group, regardless of changes in substance use. CONCLUSIONS: These findings have implications for practice, as they suggest that brief substance abuse interventions delivered in the emergency department settings may have effects beyond those targeted by the intervention. Specifically, brief substance abuse interventions may positively impact mental health, thus enhancing the quality of life among targets of the intervention.

Understanding fragility fracture patients' decision-making process regarding bisphosphonate treatment.

We aimed to understand how patients 50 years and older decided to persist with or stop osteoporosis (OP) treatment. Processes related to persisting with or stopping OP treatments are complex and dynamic. The severity and risks and harms related to untreated clinical OP and the favorable benefit-to-risk profile for OP treatments should be reinforced. INTRODUCTION: Older adults with fragility fracture and clinical OP are at high risk of recurrent fracture, and treatment reduces this risk by 50 %. However, only 20 % of fracture patients are treated for OP and half stop treatment within 1 year. We aimed to understand how older patients with new fractures decided to persist with or stop OP treatment over 1 year. METHODS: We conducted a grounded theory study of patients 50 years and older with upper extremity fracture who started bisphosphonates and then reported persisting with or stopping treatment at 1 year. We used theoretical sampling to identify patients who could inform emerging concepts until data saturation was achieved and analyzed these data using constant comparison. RESULTS: We conducted 21 interviews with 12 patients. Three major themes emerged. First, patients perceived OP was not a serious health condition and considered its impact negligible. Second, persisters and stoppers differed in weighting the risks vs benefits of treatments, where persisters perceived less risk and more benefit. Persisters considered treatment "required" while stoppers often deemed treatment "optional." Third, patients could change treatment status even 1-year post-fracture because they re-evaluated severity and impact of OP vs risks and benefits of treatments over time. CONCLUSIONS: The processes and reasoning related to persisting with or stopping OP treatments post-fracture are complex and dynamic. Our findings suggest two areas of leverage for healthcare providers to reinforce to improve persistence: (1) the severity and risks and harms related to untreated clinical OP and (2) the favorable benefit-to-risk profile for OP treatments.

Ultrafast Formation of a Charge Density Wave State in 1T-TaS_{2}: Observation at Nanometer Scales Using Time-Resolved X-Ray Diffraction.

Femtosecond time-resolved x-ray diffraction is used to study a photoinduced phase transition between two charge density wave (CDW) states in 1T-TaS_{2}, namely the nearly commensurate (NC) and the incommensurate (I) CDW states. Structural modulations associated with the NC-CDW order are found to disappear within 400 fs. The photoinduced I-CDW phase then develops through a nucleation and growth process which ends 100 ps after laser excitation. We demonstrate that the newly formed I-CDW phase is fragmented into several nanometric domains that are growing through a coarsening process. The coarsening dynamics is found to follow the universal Lifshitz-Allen-Cahn growth law, which describes the ordering kinetics in systems exhibiting a nonconservative order parameter.

Validation of administrative data case definitions for gestational diabetes mellitus.

AIM: To examine, using administrative data, the validity of two algorithms for identifying gestational diabetes mellitus: 1) the current National Diabetes Surveillance System algorithm for excluding gestational diabetes cases and 2) gestational diabetes-specific ICD codes in the delivery-related hospitalization. METHODS: This was a retrospective study of all women, aged 18-54 years, residing in Alberta, Canada, with singleton deliveries between 1 April 1999 and 31 March 2010. We linked Alberta Perinatal Health Program data on all deliveries to administrative claims data from Alberta Health using the mother's personal health number. For both gestational diabetes algorithms, we calculated the sensitivity, specificity, positive predictive value, negative predictive value and agreement, using gestational diabetes identified in the Alberta Perinatal Health Program as the 'gold standard'. RESULTS: Our study sample consisted of 411 390 deliveries for 273 152 women. The mean (sd) age was 29.1 (5.6) years and 82.3% of the women were white. Crude rates of gestational diabetes were 3.9% (16 215 cases), 1.3% (5189 cases) and 4.0% (16 440 cases) according to the Alberta Perinatal Health Program, National Diabetes Surveillance System and ICD code-based algorithms, respectively. Compared with the Alberta Perinatal Health Program database, the National Diabetes Surveillance System algorithm had a sensitivity of 25% and specificity of 100%, whereas the gestational diabetes-specific ICD code-based algorithm had a sensitivity of 86% and specificity of 99%. CONCLUSIONS: The National Diabetes Surveillance System algorithm underestimates the number of gestational diabetes cases. A more valid mechanism to identify gestational diabetes prevalence using health administrative data is the use of gestational diabetes-specific ICD-9/10 codes in the delivery hospitalization.

Validation of administrative and clinical case definitions for gestational diabetes mellitus against laboratory results.

AIM: To examine the validity of International Classification of Disease, version 10 (ICD-10) codes for gestational diabetes mellitus in administrative databases (outpatient and inpatient), and in a clinical perinatal database (Alberta Perinatal Health Program), using laboratory data as the 'gold standard'. METHODS: Women aged 12-54 years with in-hospital, singleton deliveries between 1 October 2008 and 31 March 2010 in Alberta, Canada were included in the study. A gestational diabetes diagnosis was defined in the laboratory data as ≥2 abnormal values on a 75-g oral glucose tolerance test or a 50-g glucose screen ≥10.3 mmol/l. RESULTS: Of 58 338 pregnancies, 2085 (3.6%) met gestational diabetes criteria based on laboratory data. The gestational diabetes rates in outpatient only, inpatient only, outpatient or inpatient combined, and Alberta Perinatal Health Program databases were 5.2% (3051), 4.8% (2791), 5.8% (3367) and 4.8% (2825), respectively. Although the outpatient or inpatient combined data achieved the highest sensitivity (92%) and specificity (97%), it was associated with a positive predictive value of only 57%. The majority of the false-positives (78%), however, had one abnormal value on oral glucose tolerance test, corresponding to a diagnosis of impaired glucose tolerance in pregnancy. CONCLUSIONS: The ICD-10 codes for gestational diabetes in administrative databases, especially when outpatient and inpatient databases are combined, can be used to reliably estimate the burden of the disease at the population level. Because impaired glucose tolerance in pregnancy and gestational diabetes may be managed similarly in clinical practice, impaired glucose tolerance in pregnancy is often coded as gestational diabetes.

Patterns of glucose-lowering therapies and neonatal outcomes in the treatment of gestational diabetes in Canada, 2009-2014.

AIM: To examine patterns of use of different glycaemic control agents for treating gestational diabetes mellitus. METHODS: This was a large, retrospective, population-based cohort study of pregnant women with gestational diabetes from Alberta, Canada. We linked data from the Alberta Vital Statistics - Birth database with administrative claims data. Alberta Vital Statistics - Birth data were used to identify births that occurred between 1 January 2009 and 31 December 2014. We used International Classification of Diseases version 9/10 codes to identify women with gestational diabetes, and we excluded women with pre-existing diabetes. RESULTS: Our cohort consisted of 16 857 women with gestational diabetes, with a total of 18 761 birth events between 2009 and 2014. Over the study period, the proportion of women with gestational diabetes who were treated with glycaemic control therapies increased from 25.0% to 31.4% (P<0.0001). The number of pregnancies treated with insulin only increased (from 23.6% to 28.3%; P<0.0001), as did the number treated with metformin, +/- insulin (from 1.4% to 3.2%; P<0.0001). Rates of large-for-gestational-age infants were significantly higher among pregnancies treated with insulin only (17%) or metformin (16.5%) than among pregnancies that did not receive any pharmacological treatment (12.8%). CONCLUSIONS: Our findings show increasing use of insulin and metformin in women with gestational diabetes. Rates of large-for-gestational-age infants were similar among pregnant women receiving either pharmacological treatment, and higher than among pregnant women who did not receive any pharmacological treatment. Future research should explore the long-term outcomes and safety of metformin as an alternative for treating gestational diabetes.

A large outbreak of acute gastroenteritis in Shippensburg, Pennsylvania, 1972 revisited: evidence for common source exposure to a recombinant GII.Pg/GII.3 norovirus.

Historical outbreaks can be an important source of information in the understanding of norovirus evolution and epidemiology. Here, we revisit an outbreak of undiagnosed gastroenteritis that occurred in Shippensburg, Pennsylvania in 1972. Nearly 5000 people fell ill over the course of 10 days. Symptoms included diarrhea, vomiting, stomach cramps, and fever, lasting for a median of 24 h. Using current techniques, including next-generation sequencing of full-length viral genomic amplicons, we identified an unusual norovirus recombinant (GII.Pg/GII.3) in nine of 15 available stool samples from the outbreak. This particular recombinant virus has not been reported in recent decades, although GII.3 and GII.Pg genotypes have been detected individually in current epidemic strains. The consensus nucleotide sequences were nearly identical among the four viral genomes analysed, although each strain had three to seven positions in the genome with heterogenous non-synonymous nucleotide subpopulations. Two of these resulting amino acid polymorphisms were conserved in frequency among all four cases, consistent with common source exposure and successful transmission of a mixed viral population. Continued investigation of variant nucleotide populations and recombination events among ancestral norovirus strains such as the Shippensburg virus may provide unique insight into the origin of contemporary strains.

Palaeoecological records of coral community development on a turbid, nearshore reef complex: baselines for assessing ecological change.

Understanding past coral community development and reef growth is crucial for placing contemporary ecological and environmental change within appropriate reef-building timescales. On Australia's Great Barrier Reef (GBR), coral reefs situated within coastal inner-shelf zones are a particular priority. This is due to their close proximity to river point sources, and therefore susceptibility to reduced water quality discharged from coastal catchments, many of which have been modified following European settlement (ca. 1850 AD). However, the extent of water-quality decline and its impacts on the GBR's inner-shelf reefs remain contentious. In this study, palaeoecological coral assemblage records were developed for five proximal coral reefs situated within a nearshore turbid-zone reef complex on the central GBR. A total of 29 genera of Scleractinia were identified from the palaeoecological inventory of the reef complex, with key contributions to reef-building made by Acropora, Montipora, and Turbinaria. Discrete intervals pre- and post-dating European settlement, but associated with equivalent water depths, were identified using Bayesian age-depth modelling, enabling investigation of competing ideas of the main drivers of nearshore coral assemblage change. Specifically, we tested the hypotheses that changes in the composition of nearshore coral assemblages are: (1) intrinsically driven and linked to vertical reef development towards sea level, and (2) the result of changes in water quality associated with coastal river catchment modification. Our records found no discernible evidence of change in the generic composition of coral assemblages relative to European settlement. Instead, two distinctive depth-stratified assemblages were identified. This study demonstrates the robust nature of nearshore coral communities under reported water-quality decline and provides a useful context for the monitoring and assessment of ecological change on reefs located within the most nearshore turbid-zone environments of the central GBR.

Contrasting evolutionary histories of MHC class I and class II loci in grouse--effects of selection and gene conversion.

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

Thinking outside the shunt-sterile CSF malabsorption in pilocytic astrocytomas: case series and review of the literature.

INTRODUCTION: Ventriculoperitoneal (VP) shunt insertion is the most common cerebrospinal fluid (CSF) diversionary procedure used for the treatment of chronic hydrocephalus. Sterile CSF ascites is a rare complication of VP shunt insertion. This can arise from either an overproduction of CSF or inadequate filtration of CSF at the level of the peritoneum. By either mechanism, the development of CSF ascites requires an intact VP shunt. OBJECTIVE: The authors discuss two paediatric cases diagnosed with suprasellar pilocytic astrocytomas treated with platinum-based chemotherapy, who subsequently developed sterile CSF ascites. We review the literature with regard to CSF malabsorption and discuss it as a contributing factor to shunt malfunction. CONCLUSION: CSF malabsorption with resultant ascites is a rare complication of VP shunting with many etiologies. Two common predisposing factors included the use of platinum-based chemotherapeutic agents, as well as the specific neuropathology. Further analysis of these two entities is needed in order to elucidate their role in contributing to the development of CSF ascites in this patient cohort.

Widespread correction of central nervous system disease after intracranial gene therapy in a feline model of Sandhoff disease.

Sandhoff disease (SD) is caused by deficiency of N-acetyl-ß-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.