Activated carbon amendment of sand in the base of a permeable pavement reduces total nitrogen and nitrate leaching.

Urban runoff from impermeable surfaces contains various pollutants. Stormwater samples were collected for one year from car parks on the campus of Newcastle University, located in northeast England, to monitor seasonal variation in stormwater properties and leachate quality following stormwater percolation through pilot-scale, outdoor permeable pavements. The pilot study compared an innovative 'pollution munching' permeable pavement with 2 % activated carbon (AC) amendment in the sand base with a conventional, un-amended sand base permeable pavement. Faecal coliforms were detected in stormwater at an average value of 3.75 ± 0.79 log10 CFUs per 100 mL. The permeable pavements without and with AC had mean log removal values of 0.81 ± 0.35 and 0.70 ± 0.35 for these faecal bacteria. The absence of genetic markers for human host associated Bacteroides (HF183) in eleven out of twelve stormwater samples showed that the faecal bacteria were mainly from animal sources. 16S rRNA gene sequencing results confirmed the presence of nitrifying bacteria from the genera Nitrosomonas, Nitrobacter, Nitrosococcus, Nitrospira, and Nitrosospira in stormwater. Nitrification and nitrate leaching was more notable for the conventional permeable pavement and may pose a groundwater pollution risk. Two percent AC amendment of the sand base reduced nitrate and total nitrogen leaching significantly compared with the conventional permeable pavement, by 57 ± 15 % and 40 ± 20 %, respectively. The AC amendment also resulted in significantly reduced Cu and DOC leaching, and lesser accumulation of PAHs by passive samplers embedded in the permeable pavement base. Hydraulic tests showed that the AC amended base layer still met the design specifications for permeable pavements, making it a promising proposition for pollution reduction in Sustainable Drainage Systems (SuDS).

Effective removal of iron, nutrients, micropollutants, and faecal bacteria in constructed wetlands cotreating mine water and sewage treatment plant effluent.

Regulators in England and Wales have set new targets under the Environment Act 2021 for freshwater quality by 2038 that include halving the length of rivers polluted by harmful metals from abandoned mines and reducing phosphorus loadings from treated wastewater by 80%. In this context, an intriguing win-win opportunity exists in the removal of iron from abandoned mines and phosphate from small sewage treatment plants by coprecipitation in constructed wetlands (CWs). We investigated such a CW located at Lamesley, Northeast England, which cotreats abandoned coal mine and secondary-treated sewage treatment plant effluents. We assessed the removal of nutrients, heavy metals, organic micropollutants, and faecal coliforms by the CW, and characterized changes in the water bacteriology comprehensively using environmental DNA. The CW effectively removed ammonium-nitrogen, phosphorus, iron, and faecal coliforms by an average of 86, 74, 98, and 75%, respectively, to levels below or insignificantly different from those in the receiving river. The CW also effectively removed micropollutants such as acetaminophen, caffeine, and sulpiride by 70-100%. Molecular microbiology methods showed successful conversion of sewage and mine water microbiomes into a freshwater microbiome. Overall, the CW significantly reduced impacts on the rural water environment with minimal operational requirements.

Determining the neuronal ensembles underlying sex-specific social impairments following adolescent intermittent ethanol exposure.

Binge drinking during adolescence can have behavioral and neurobiological consequences. We have previously found that adolescent intermittent ethanol (AIE) exposure produces sex-specific social alterations indexed via decreases of social investigation and/or social preference in rats. The prelimbic cortex (PrL) regulates social interaction, and alterations within the PrL resulting from AIE may contribute to social alterations. The current study sought to determine whether AIE-induced PrL dysfunction underlies decreases in social interaction evident in adulthood. We first examined social interaction-induced neuronal activation of the PrL and several other regions of interest (ROIs) implicated in social interaction. Adolescent male and female cFos-LacZ rats were exposed to water (control) or ethanol (4 g/kg, 25% v/v) via intragastric gavage every other day between postnatal day (P) 25 and 45 (total 11 exposures). Since cFos-LacZ rats express ß-galactosidase (ß-gal) as a proxy for Fos, activated cells that express of ß-gal can be inactivated by Daun02. In most ROIs, expression of ß-gal was elevated in socially tested adult rats relative to home cage controls, regardless of sex. However, decreased social interaction-induced ß-gal expression in AIE-exposed rats relative to controls was evident only in the PrL of males. A separate cohort underwent PrL cannulation surgery in adulthood and was subjected to Daun02-induced inactivation. Inactivation of PrL ensembles previously activated by social interaction reduced social investigation in control males, with no changes evident in AIE-exposed males or females. These findings highlight the role of the PrL in male social investigation and suggest an AIE-associated dysfunction of the PrL that may contribute to reduced social investigation following adolescent ethanol exposure.

Fixed-bed biofilter for polluted surface water treatment using chitosan impregnated-coconut husk biochar.

Pelletizing biochar enables its use as a biofilter medium for polluted canal water treatment. Coconut husk biochar pellets and their modification with chitosan (CHC) were compared with conventional activated carbon pellets and gravel. The biofilter columns with these media were operated with a hydraulic loading rate of 0.1 m3/m2∙h. CHC showed the highest potential to reduce phosphate and nitrogen, via the adsorption process in the first week of filtration and later enhanced by biodegradation, to achieve removal efficiencies of 61.70 and 54.37% for these two key nutrients, respectively, over five weeks of biofilter operation. The predominant bacteria in the biofilter communities were characterized at the end of the experiments by next generation sequencing and quantitative polymerase chain reaction analysis. The biofilter communities included ammonium oxidizing, nitrite oxidizing, denitrifying, polyphosphate accumulating and denitrifying phosphate-accumulating bacteria that benefit nutrient removal. The CHC biofilter also effectively removed micropollutants, including pharmaceuticals.

Environmental DNA clarifies impacts of combined sewer overflows on the bacteriology of an urban river and resulting risks to public health.

There is no reference of microbiological water quality in the European Union's Water Framework Directive, adapted into English law, and consequently microbial water quality is not routinely monitored in English rivers, except for two recently designated bathing water sites. To address this knowledge gap, we developed an innovative monitoring approach for quantitative assessment of combined sewer overflow (CSO) impacts on the bacteriology of receiving rivers. Our approach combines conventional and environmental DNA (eDNA) based methods to generate multiple lines of evidence for assessing risks to public health. We demonstrated this approach by investigating spatiotemporal variation in the bacteriology of the Ouseburn in northeast England for different weather conditions in the summer and early autumn of the year 2021 across eight sampling locations that comprised rural, urban, and recreational land use settings. We characterized pollution source attributes by collecting sewage from treatment works and CSO discharge at the peak of a storm event. CSO discharge was characterized by log10 values per 100 mL (average ± stdev) of 5.12 ± 0.03 and 4.90 ± 0.03 for faecal coliforms and faecal streptococci, and 6.00 ± 0.11 and 7.78 ± 0.04 for rodA and HF183 genetic markers, for E. coli and human host associated Bacteroides, respectively, indicating about 5 % sewage content. SourceTracker analysis of sequencing data attributed 72-77 % of bacteria in the downstream section of the river during a storm event to CSO discharge sources, versus only 4-6 % to rural upstream sources. Data from sixteen summer sampling events in a public park exceeded various guideline values for recreational water quality. Quantitative microbial risk assessment (QMRA) predicted a median and 95th percentile risk of 0.03 and 0.39, respectively, of contracting a bacterial gastrointestinal disease when wading and splashing around in the Ouseburn. We show clearly why microbial water quality should be monitored where rivers flow through public parks, irrespective of their bathing water designation.

Determining the neuronal ensembles underlying sex-specific social impairments following adolescent intermittent ethanol exposure.

Binge drinking during adolescence can have behavioral and neurobiological consequences. We have previously found that adolescent intermittent ethanol (AIE) exposure produces a sex-specific social impairment in rats. The prelimbic cortex (PrL) regulates social behavior, and alterations within the PrL resulting from AIE may contribute to social impairments. The current study sought to determine whether AIE-induced PrL dysfunction underlies social deficits in adulthood. We first examined social stimulus-induced neuronal activation of the PrL and several other regions of interest implicated in social behavior. Male and female cFos-LacZ rats were exposed to water (control) or ethanol (4 g/kg, 25% v/v) via intragastric gavage every other day between postnatal day (P) 25 and 45 (total 11 exposures). Since cFos-LacZ rats express ß-galactosidase (ß-gal) as a proxy for cFos, activated cells that express of ß-gal can be inactivated by Daun02. ß-gal expression in most ROIs was elevated in socially tested adult rats relative to home cage controls, regardless of sex. However, differences in social stimulus-induced ß-gal expression between controls and AIE-exposed rats was evident only in the PrL of males. A separate cohort underwent PrL cannulation surgery in adulthood and were subjected to Daun02-induced inactivation. Inactivation of PrL ensembles previously activated by a social stimulus led to a reduction of social behavior in control males, with no changes evident in AIE-exposed males or females. These findings highlight the role of the PrL in male social behavior and suggest an AIE-associated dysfunction of the PrL may contribute to social deficits following adolescent ethanol exposure.

Mobilization of arsenic from As-containing iron minerals under irrigation: Effects of exogenous substances, redox condition, and intermittent flow.

Irrigation activities can cause strong geochemical and hydrological fluctuations in the unsaturated zone, and affect arsenic (As) migration and transformation. The As geochemical cycle in the unsaturated zone is coupled with that of iron minerals through sorption-desorption, coprecipitation and redox processes. Dynamic batch experiments and wetting-drying cycling column experiments were conducted to evaluate As mobilization behaviors under the effects of exogenous substances, redox condition and intermittent flow. Our results show that As release under exogenous substances carried by irrigation (e.g., phosphate, carbonate, fulvic acid, humic acid, etc.) followed three trends with the types of exogenous inputs. Inorganic anions and organic matter resulted in opposite trends of arsenate release in different redox conditions. In anoxic environments, As(V) release was favored by the addition of phosphate and carbonate, while in oxic environments, the mobilization of As(V) was promoted by the addition of fulvic acid (FA). Further, intermittent irrigation promoted the reductive dissolution of Fe oxides and the mobilization of As. The addition of humic acid (HA) resulted in the mobilization of arsenate as As-Fe-HA ternary complexes. The mechanism of arsenic mobilization under irrigation has importance for prevention of arsenic exposure through soil to food chain transfer in typical high arsenic farmland.

Attenuation of bacterial hazard indicators in the subsurface of an informal settlement and their application in quantitative microbial risk assessment.

Pit latrines provide essential onsite sanitation services to over a billion people, but there are concerns about their role in infectious disease transmission, and impacts on groundwater resources. We conducted fieldwork in an informal settlement in Dar es Salaam, where cholera is endemic. We combined plate counting with portable MinION sequencing and quantitative polymerase chain reaction (qPCR) methods for characterization of bacteria in pit latrine sludge, leachate, shallow and deep groundwater resources. Pit latrine sludge was characterized by log10 marker gene concentrations per 100 mL of 11.2 ± 0.2, 9.9 ± 0.9, 6.0 ± 0.3, and 4.4 ± 0.8, for total bacteria (16S rRNA), E. coli (rodA), human-host-associated Bacteroides (HF183), and Vibrio cholerae (ompW), respectively. The ompW gene observations suggested 5 % asymptomatic Vibrio cholerae carriers amongst pit latrine users. Pit leachate percolation through one-meter-thick sand beds attenuated bacterial hazard indicators by 1 to 4 log10 units. But first-order removal rates derived from these data substantially overestimated the longer-range hazard attenuation in the sand aquifers. Cooccurrence of human sewage marker gene HF183 in all shallow groundwater samples testing positive for ompW genes demonstrated the human origin of Vibrio cholerae hazards in the subsurface. All borehole water samples tested negative for ompW and HF183 genes, but 16S rRNA gene sequencing data suggested ingress of faecal pollution into boreholes at the peak of the "long rainy season". Quantitative microbial risk assessment (QMRA) predicted a gastrointestinal disease burden of 0.05 DALY per person per year for the community, well above WHO targets of 10-4-10-6 DALY for disease related to drinking water.

A prognostic model for failure and worsening after lumbar microdiscectomy: a multicenter study from the Norwegian Registry for Spine Surgery.

OBJECTIVE: To develop a prognostic model for failure and worsening 1 year after surgery for lumbar disc herniation. METHODS: This multicenter cohort study included 11,081 patients operated with lumbar microdiscectomy, registered at the Norwegian Registry for Spine Surgery. Follow-up was 1 year. Uni- and multivariate logistic regression analyses were used to assess potential prognostic factors for previously defined cut-offs for failure and worsening on the Oswestry Disability Index scores 12 months after surgery. Since the cut-offs for failure and worsening are different for patients with low, moderate, and high baseline ODI scores, the multivariate analyses were run separately for these subgroups. Data were split into a training (70%) and a validation set (30%). The model was developed in the training set and tested in the validation set. A prediction (%) of an outcome was calculated for each patient in a risk matrix. RESULTS: The prognostic model produced six risk matrices based on three baseline ODI ranges (low, medium, and high) and two outcomes (failure and worsening), each containing 7 to 11 prognostic factors. Model discrimination and calibration were acceptable. The estimated preoperative probabilities ranged from 3 to 94% for failure and from 1 to 72% for worsening in our validation cohort. CONCLUSION: We developed a prognostic model for failure and worsening 12 months after surgery for lumbar disc herniation. The model showed acceptable calibration and discrimination, and could be useful in assisting physicians and patients in clinical decision-making process prior to surgery.

Endoscopic hemostasis makes the difference: Angiographic treatment in patients with lower gastrointestinal bleeding.

BACKGROUND: The large majority of gastrointestinal bleedings subside on their own or after endoscopic treatment. However, a small number of these may pose a challenge in terms of therapy because the patients develop hemodynamic instability, and endoscopy does not achieve adequate hemostasis. Interventional radiology supplemented with catheter angiography (CA) and transarterial embolization have gained importance in recent times. AIM: To evaluate clinical predictors for angiography in patients with lower gastrointestinal bleeding (LGIB). METHODS: We compared two groups of patients in a retrospective analysis. One group had been treated for more than 10 years with CA for LGIB (n = 41). The control group had undergone non-endoscopic or endoscopic treatment for two years and been registered in a bleeding registry (n = 92). The differences between the two groups were analyzed using decision trees with the goal of defining clear rules for optimal treatment. RESULTS: Patients in the CA group had a higher shock index, a higher Glasgow-Blatchford bleeding score (GBS), lower serum hemoglobin levels, and more rarely achieved hemostasis in primary endoscopy. These patients needed more transfusions, had longer hospital stays, and had to undergo subsequent surgery more frequently (P < 0.001). CONCLUSION: Endoscopic hemostasis proved to be the crucial difference between the two patient groups. Primary endoscopic hemostasis, along with GBS and the number of transfusions, would permit a stratification of risks. After prospective confirmation of the present findings, the use of decision trees would permit the identification of patients at risk for subsequent diagnosis and treatment based on interventional radiology.

Trunk Muscle Endurance in Individuals With and Without a History of Anterior Cruciate Ligament Reconstruction.

ABSTRACT: Werner, DM and Barrios, JA. Trunk muscle endurance in individuals with and without a history of anterior cruciate ligament reconstruction. J Strength Cond Res 35(1): 118-123, 2021-Anterior cruciate ligament (ACL) rupture is one of the most common knee injuries and often leads to surgery. Second injury after an ACL reconstruction (ACLR) is a major risk after rehabilitation, and may be linked to persistent postoperative deficits in muscular strength and endurance. Trunk muscle endurance has not been well studied after ACLR. Therefore, the purpose of this study was to compare trunk endurance using the established McGill testing battery in 20 individuals who had previously undergone ACLR at least 1 year before with 20 controls matched for sex frequency, limb dominance, age, body mass index, and activity level. Four static positional holds to failure were performed in random order, with time in seconds recorded as the primary dependent variable. Mann-Whitney U tests using an alpha level of 0.05 were conducted comparing hold times for all positions between groups. Effect sizes were also calculated between groups. Deficits in trunk extension endurance were observed in the surgical group. The results of this study suggest that contemporary rehabilitation schemes after ACLR do not fully address trunk endurance deficits. Health care professionals delivering postoperative rehabilitation after ACLR may consider direct assessment of trunk endurance and targeted exercise training to address potential deficits.

Can a Successful Outcome After Surgery for Lumbar Disc Herniation Be Defined by the Oswestry Disability Index Raw Score?

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To investigate (1) the discriminative ability and cutoff estimates for success 12 months after surgery for lumbar disc herniation on the Oswestry Disability Index (ODI) raw score compared with a change and a percentage change score and (2) to what extent these clinical outcomes depend on the baseline disability. METHODS: A total of 6840 patients operated for lumbar disc herniation from the Norwegian Registry for Spine Surgery (NORspine) were included. In receiver operating characteristic (ROC) curve analyses, a global perceived effect (GPE) scale (1-7) was used an external anchor. Success was defined as categories 1-2, "completely recovered" and "much better." Cutoffs for success for subgroups with different preoperative disability were also estimated. RESULTS: When defining success after surgery for lumbar disc herniation, the accuracy (sensitivity, specificity, area under the curve, 95% CI) for the ODI raw score (0.83, 0.87, 0.930, 0.924-0.937) was comparable to the ODI percentage change score (0.85, 0.85, 0.925, 0.918-0.931), and higher than the ODI change score (0.79, 0.73, 0.838, 0.830-0.852). The cutoff for success was highly dependent on the amount of baseline disability (low-high), with cutoffs ranging from 13 to 28 for the ODI raw score and 39% to 66% for ODI percentage change. The ODI change score (points) was not as accurate. CONCLUSION: The 12-month ODI raw score, like the ODI percentage change score, can define a successful outcome with excellent accuracy. Adjustment for the baseline ODI score should be performed when comparing outcomes across groups, and one should consider using cutoffs according to preoperative disability (low, medium, high ODI scores).

Predicted Impact of Climate Change on Trihalomethanes Formation in Drinking Water Treatment.

Quantitative predictions of impacts on public water supplies are essential for planning climate change adaptations. Monitoring data from five full-scale Scottish drinking water treatment plants (DWTPs) showed that significant correlations exist between conditionally carcinogenic trihalomethanes (THMs) levels, water temperature (r = 0.812, p = 0.0013) and dissolved organic carbon (DOC) (r = 0.892, p < 0.0001), respectively. The strong seasonality of these parameters demonstrated how climate can influence THMs formation. We quantified with laboratory experiments the sensitivity of THMs formation to changes in water temperature and DOC concentration. The laboratory data accurately reproduced real-world THM formation in the DWTPs. We then combined these validated relationships with information from the literature about future trends in mean summer temperatures and surface water DOC in the British Isles, to estimate future global warming impacts on THMs formation in DWTPs that use chlorine for disinfection. An increase in mean summer temperatures will likely increase THM formation, with a 1.8 °C temperature increase and 39% THMs increase by 2050 representing our mid-range scenario. Such an increase has major implications to potable water around the world, either an increased health risk or increased water treatment costs to maintain an equivalent quality potable supply.

Flow-cytometric quantification of microbial cells on sand from water biofilters.

Rapid quantification of absolute microbial cell abundances is important for a comprehensive interpretation of microbiome surveys and crucial to support theoretical modelling and the design of engineered systems. In this paper, we propose a protocol specifically optimised for the quantification of microbial abundances in water biofilters using flow cytometry (FCM). We optimised cell detachment from sand biofilter particles for FCM quantification through the evaluation of five chemical dispersants (NaCl, Triton-X100, CaCl2, sodium pyrophosphate (PP), Tween 80 combined with PP), different mechanical pre-treatments (low and high energy sonication and shaking) and two fixation methods (glutaraldehyde and ethanol). The developed protocol was cross-compared using other established and commonly employed methods for biomass quantification in water filter samples (adenosine triphosphate (ATP) quantification, real-time quantitative PCR (qPCR) and volatile solids (VS)). The highest microbial count was obtained by detaching the biofilm from biofilter grains and dispersing clusters into singles cells using Tween 80 and sodium pyrophosphate combined with four steps of high energy sonication (27W, for 80 s each step); glutaraldehyde was shown to be the best fixative solution. The developed protocol was reliable and highly reproducible and produced results that are comparable to data from alternative quantification methods. Indeed, high correlations were found with trends obtained through ATP and qPCR (ρ = 0.98 and ρ = 0.91) measurements. The VS content was confirmed as an inaccurate method to express biomass in sand samples since it correlated poorly with all the other three methods (ρ = 0.005 with FCM, 0.002 with ATP and 0.177 with qPCR). FCM and ATP showed the strongest agreement between absolute counts with a slope of the correlation equal to 0.7, while qPCR seemed to overestimate cell counts by a factor of ten. The rapidity and reproducibility of the method developed make its application ideal for routine quantification of microbial cell abundances on sand from water biofilters and thus useful in revealing the ecological patterns and quantifying the metabolic kinetics involved in such systems.

Endoscopic and angiographic management of lower gastrointestinal bleeding: Review of the published literature.

Lower gastrointestinal bleeding is common and occurs often in elderly patients. In rare cases it is associated with hemorrhagic shock. A large number of such bleedings, which are often caused by colon diverticula, subside spontaneously. Alternatively they can be treated by endoscopic procedures successfully. Given the aging population of our society, the rising incidence of lower gastrointestinal tract bleeding and new anticoagulant therapies, some of the bleedings tend to be severe. Colonoscopy is the established standard procedure for the diagnosis and treatment of lower gastrointestinal bleeding. However, a small number of patients experience re-bleeding or shock; their bleeding does not resolve spontaneously and cannot be treated successfully by endoscopic procedures. In such patients, interventional radiology is very useful for the detection of bleeding and the achievement of hemostasis. Against this background we performed a literature search using PubMed to identify all relevant studies focused on the endoscopic and radiological management of lower gastrointestinal bleeding and present recent conclusions on the subject.

Surgery for Herniated Lumbar Disc in Daily Tobacco Smokers: A Multicenter Observational Study.

OBJECTIVE: To compare clinical outcomes at 1 year following single-level lumbar microdiscectomy in daily tobacco smokers and nonsmokers. METHODS: Data were collected through the Norwegian Registry for Spine Surgery. The primary endpoint was a change in the Oswestry Disability Index (ODI) at 1 year. Secondary endpoints were change in quality of life measured with EuroQol 5 Dimensions (EQ-5D), leg and back pain measured with a numerical rating scale (NRS), and rates of surgical complications. RESULTS: A total of 5514 patients were enrolled, including 3907 nonsmokers and 1607 smokers. A significant improvement in ODI was observed for the entire cohort (mean, 31.1 points; 95% confidence interval [CI], 30.4-31.8; P < 0.001). Nonsmokers experienced a greater improvement in ODI at 1 year compared with smokers (mean, 4.1 points; 95% CI, 2.5-5.7; P < 0.001). Nonsmokers were more likely to achieve a minimal important change (MIC), defined as an ODI improvement of ≥10 points, compared with smokers (85.5% vs. 79.5%; P < 0.001). Nonsmokers experienced greater improvements in EQ-5D (mean difference, 0.068; 95% CI, 0.04-0.09; P < 0.001), back pain NRS (mean difference, 0.44; 95% CI, 0.21-0.66; P < 0.001), and leg pain NRS (mean difference, 0.54; 95% CI, 0.31-0.77; P < 0.001). There was no difference between smokers and nonsmokers in the overall complication rate (6.2% vs. 6.7%; P = 0.512). Smoking was identified as a negative predictor for ODI change in a multiple regression analysis (P < 0.001). CONCLUSIONS: Nonsmokers reported a greater improvement in ODI at 1 year following microdiscectomy, and smokers were less likely to experience an MIC. Nonetheless, significant improvement was also found among smokers.

Criteria for failure and worsening after surgery for lumbar disc herniation: a multicenter observational study based on data from the Norwegian Registry for Spine Surgery.

PURPOSE: In clinical decision-making, it is crucial to discuss the probability of adverse outcomes with the patient. A large proportion of the outcomes are difficult to classify as either failure or success. Consequently, cutoff values in patient-reported outcome measures (PROMs) for "failure" and "worsening" are likely to be different from those of "non-success". The aim of this study was to identify dichotomous cutoffs for failure and worsening, 12 months after surgical treatment for lumbar disc herniation, in a large registry cohort. METHODS: A total of 6840 patients with lumbar disc herniation were operated and followed for 12 months, according to the standard protocol of the Norwegian Registry for Spine Surgery (NORspine). Patients reporting to be unchanged or worse on the Global Perceived Effectiveness (GPE) scale at 12-month follow-up were classified as "failure", and those considering themselves "worse" or "worse than ever" after surgery were classified as "worsening". These two dichotomous outcomes were used as anchors in analyses of receiver operating characteristics (ROC) to define cutoffs for failure and worsening on commonly used PROMs, namely, the Oswestry Disability Index (ODI), the EuroQuol 5D (EQ-5D), and Numerical Rating Scales (NRS) for back pain and leg pain. RESULTS: "Failure" after 12 months for each PROM, as an insufficient improvement from baseline, was (sensitivity and specificity): ODI change <13 (0.82, 0.82), ODI% change <33% (0.86, 0.86), ODI final raw score >25 (0.89, 0.81), NRS back-pain change <1.5 (0.74, 0.86), NRS back-pain % change <24 (0.85, 0.81), NRS back-pain final raw score >5.5 (0.81, 0.87), NRS leg-pain change <1.5 (0.81, 0.76), NRS leg-pain % change <39 (0.86, 0.81), NRS leg-pain final raw score >4.5 (0.91, 0.85), EQ-5D change <0.10 (0.76, 0.83), and EQ-5D final raw score >0.63 (0.81, 0.85). Both a final raw score >48 for the ODI and an NRS >7.5 were indicators for "worsening" after 12 months, with acceptable accuracy. CONCLUSION: The criteria with the highest accuracy for defining failure and worsening after surgery for lumbar disc herniation were an ODI percentage change score <33% for failure and a 12-month ODI raw score >48. These cutoffs can facilitate shared decision-making among doctors and patients, and improve quality assessment and comparison of clinical outcomes across surgical units. In addition to clinically relevant improvements, we propose that rates of failure and worsening should be included in reporting from clinical trials.

Climatic, Geographic and Operational Determinants of Trihalomethanes (THMs) in Drinking Water Systems.

Trihalomethanes (THMs) are conditionally carcinogenic compounds formed during chlorine disinfection in water treatment processes around the world. THMs occur especially when source waters are subject to marine influences, high and-or regular precipitation, and elevated levels of organic matter. THMs formation is then rooted in geographic, operational and climatic factors, the relative importance of which can only be derived from large datasets and may change in the future. Ninety three full-scale Scottish water treatment plants (WTPs) were assessed from Jan 2011 to Jan 2013 to identify factors that promote THMs formation. Correlation analysis showed that ambient temperature was the primary THMs formation predictor in potable water (r2 = 0.66, p < 0.05) and water distribution systems (r2 = 0.43, p = 0.04), while dissolved organic carbon (r2 = 0.55, p < 0.001) and chloride (indicating marine influence; r2 = 0.41, p < 0.001) also affected THMs formation. GIS mapping of median THMs levels indicated brominated THMs were most prevalent in coastal areas and on islands. This real-world dataset confirms both geographic and climatic factors are key to THMs formation. If ambient temperatures increase, THMs control will become more challenging, substantiating concerns about the impact of global warming on water quality.

Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure.

Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIß subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIß P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults.

Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.