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The UK Hydrological Outlook (UKHO) is a seasonal forecast of future river flows and groundwater levels. The UKHO contains both presentations of outputs from models simulating future conditions and a high-level summary. The summary is produced by an expert panel of forecasters that considers the model outputs together with other recent hydrological and meteorological information. Whilst the skill and uncertainty of the individual models have been explored and published, this study sets out to establish the performance of the high-level summary, and presents such an assessment of the river flow forecasts at the 1-month timescale. Both qualitative and quantitative assessments are presented and compared with two naïve forecasting methods. The UKHO summary is found to have a similar Gerrity skill score to a "same as last month" forecast, an outcome that generates suggestions for improvements in how the different model outputs should be considered and presented in the high-level summary. [ABSTRACT FROM AUTHOR]

Background: Approximately one-third of patients with isolated traumatic brain injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated with increased morbidity and mortality. Its effects on long-term functional and cognitive outcomes are not as well characterized.Methods: Data from the Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively. Exclusion criteria were renal failure or malignancy, and any extracranial injury severity score >3. ATC was defined as INR > 1.3, PTT > 38 s, or platelets < 100 K, determined at baseline, and during the first 7 days of hospitalization.Results: Six hundred forty-seven patients were included; 21 % were found to have ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of ATC patients had a GCS < 8, compared with 11.3 % of non-ATC patients (p < 0.001). A significantly higher proportion of ATC patients was transfused blood products, required greater than 4L of fluids, demonstrated hyperthermia and hypothermia, were hypotensive and demonstrated elevated lactate when compared to non-ATC patients. In-hospital mortality, mean hospital length of stay, incidence of DVT and seizures were also significantly higher in ATC patients. A significantly lower portion of ATC patients had good outcomes on the GOS-E (i.e., score > 6), and the DRS (i.e., score < 2) at 180 days, for which ATC was found to be an independent predictor with binary logistic regression. ATC patients also performed significantly worse on several components of the CVLT-II at 180 days.Conclusions: ATC accompanying iTBI is associated with worse functional and cognitive outcomes at 180 days. [ABSTRACT FROM AUTHOR]

Objective: The Enhanced Recovery after Surgery Cardiac Society recommends using multimodal analgesia (MMA) for postoperative pain however, evidence-based guidelines have yet to be established. This study examines the impact of a standardized postoperative MMA pathway in reducing opioid consumption and related complications after cardiothoracic surgery (CTS). Methods: Within a multicenter healthcare system, a postoperative MMA pathway was developed and implemented at two CTS intensive care units (ICU) while the other CTS ICU opted to maintain the existing opioid-based pathway. A retrospective chart review was conducted on patients admitted to a CTS ICU within this healthcare system after conventional coronary artery bypass grafting and/or valve surgery from September 1, 2018, to June 30, 2019. Comparative analysis was conducted on patients prescribed MMA versus those managed with an opioid-based pathway. The primary outcome was total opioid consumption, converted to morphine milligram equivalents, 72-h post-surgery. Secondary outcomes included mobility within one-day post-surgery, ICU length of stay (LOS), time to first bowel movement (BM), and time to first zero Richmond Agitation-Sedation Scale (RASS). Results: Seven hundred sixty-two adults were included for final analysis. The MMA group had a higher body mass index, higher percentage of females, were more likely classified as African American and had higher scores for risk-adjusted complications. General Linear Model analysis revealed higher opioid consumption in the MMA group (Est. 0.22, p < 0.0009); however, this was not statistically significant after adjusting for differences in fentanyl usage. The MMA group was more likely to have mobility within one-day post-surgery (OR 0.44, p < 0.0001), have longer time to first BM (OR 1.93, p = 0.0011), and longer time to first zero RASS (OR 1.62, p = 0.0071). The analgesia groups were not a predictor for ICU LOS. Conclusions: Opioid consumption was not reduced secondary to this postoperative MMA pathway. The MMA group was more likely to have mobility within one-day post-surgery. Patients in the MMA group were also more likely to have prolonged time to first BM and first zero RASS. Development and evaluation of a perioperative MMA pathway should be considered. [ABSTRACT FROM AUTHOR]

Abstract: The River Kennet in southern England shows a clear diurnal signal in both water temperature and dissolved oxygen concentrations through the summer months. The water quality model QUESTOR was applied in a stepwise manner (adding modelled processes or additional data) to simulate the flow, water temperature and dissolved oxygen concentrations along a 14km reach. The aim of the stepwise model building was to find the simplest process-based model which simulated the observed behaviour accurately. The upstream boundary used was a diurnal signal of hourly measurements of water temperature and dissolved oxygen. In the initial simulations, the amplitude of the signal quickly reduced to zero as it was routed through the model; a behaviour not seen in the observed data. In order to keep the correct timing and amplitude of water temperature a heating term had to be introduced into the model. For dissolved oxygen, primary production from macrophytes was introduced to better simulate the oxygen pattern. Following the modifications an excellent simulation of both water temperature and dissolved oxygen was possible at an hourly resolution. It is interesting to note that it was not necessary to include nutrient limitation to the primary production model. The resulting model is not sufficiently proven to support river management but suggests that the approach has some validity and merits further development. [Copyright &y& Elsevier]

One achievement of the UK Land–Ocean Interaction Study (LOIS) was to link dynamic biogeochemical models of different domains, e.g. rivers, estuaries and coastal waters, and to use the linked model to investigate possible changes from the current status that might occur in the future, for example as the result of climate change. The Climate, Hydrochemistry and Economics of Surface-water Systems (CHESS) project has taken the LOIS methodology forward by exploring possible impacts of climate change on the water quality of European rivers, with the purpose of informing future catchment management. This was achieved by the application of a standard modelling framework to a set of five European catchments located in Finland (River Vantaa), United Kingdom (Yorkshire Ouse), Belgium (Dender), Italy (Enza) and Greece (Pinios). Baseline conditions were simulated using existing meteorological data from the period 1961–1990, and in all cases the modelling framework was able to reproduce key features of the flow and water quality regimes of the study catchments. The modelling framework comprised two models. The Soil Water Assessment Tool (SWAT) was used to simulate water and chemical fluxes, primarily nutrients and sediment, generated from diffuse areas and thereby provide sub-catchment inputs to an in-stream water quality model, the Quality Evaluation and Simulation Tool for River Systems (QUESTOR). QUESTOR integrated the diffuse runoff along the channel network, together with point source discharges from industry and sewage treatment works, and water abstractions for public supply, industry and agriculture. The modelling framework has been used for the baseline conditions, along with a set of six climate scenarios. These comprised four scenarios derived from different general circulation models (GCMs) representing the 2050s, and three scenarios from the same GCM representing the 2020s, 2050s and 2080s, with one scenario in both groups. Results have been explored using a range of measures to reflect the different stakeholder interests within and beyond the catchment. The results reflect the variability in present day conditions (e.g. climate, soils, agriculture and industry), and the variability in the climate scenarios, both between-catchment and between-scenario. Specific examples are: the loss of the spring snowmelt causing high flows on the Vantaa; a decrease in the already very low summer flows on the Pinios; and significant seasonal changes in nutrient losses, even though the annual change is small. [Copyright &y& Elsevier]

The catchment and river modelling undertaken within the UK Land Ocean Interaction Study programme represents the most extensive consistent exercise of this type undertaken in the UK. The calibrated model provides a quantitative assessment of the water and chemical fluxes transported by the rivers Derwent, Yorkshire Ouse, Wharfe, Aire, Don and Trent into the Humber estuary. These fluxes have been partitioned according to source (diffuse or point) for each basin, and a number of determinands. Total nitrogen from diffuse sources ranged from 92% on the largely agricultural Derwent to 38% from the industrial Don catchment. Even on catchments dominated by diffuse sources, point sources can contribute most during summer months. A quantitative assessment of the effect of in-stream processes suggests that denitrification can remove up to 40% of the total nitrogen entering the river system. A climate change scenario representing the 2050s revealed major changes in flow patterns, with all rivers showing a faster return to zero soil moisture deficit in the autumn and increased winter runoff, but a mixed picture of enhanced and reduced summer flows. Many associated fluxes may also increase, but long-term mean concentrations reduce because of the increased flows. The effect of the scenario on a river ecosystem classification was minor. Fertilizer reduction scenarios showed that even a large reduction in N applied as fertilizer (50%) resulted in much smaller reductions in the load delivered to the Humber estuary (6–16%). [Copyright &y& Elsevier]

The catchment and river modelling undertaken within the UK Land Ocean Interaction Study (LOIS) programme represents the most extensive consistent exercise of this type undertaken in the UK. The calibrated model provides a quantitative assessment of the water and chemical fluxes transported by the rivers Derwent, Yorkshire Ouse, Wharfe, Aire, Don and Trent into the Humber estuary, i.e. a total drainage area of almost 18 000 km2 (almost 15% of the area of England) with 2088 km of modelled river. The model simulated flow, temperature, pH, suspended sediment, dissolved oxygen, biochemical oxygen demand, particulate organic nitrogen, ammonium, ammonia, nitrite, nitrate, zinc (dissolved and particulate), lindane and atrazine. For all rivers, except the Trent, simulations were for the period 1985–1995; the simulation period for the Trent was 1998–1995. The modelling used routine monitoring data collect by the England and Wales Environment Agency, for both calibration and validation, with other data sets mainly collated by the LOIS River-Atmosphere Coastal Study (RACS) data centre (e.g. land use, soils, river network). A stepwise model development started with a basic water quality model driven by observed in-stream water quality, and resulted in the development of a LOIS specific version of the in-stream model Quality Evaluation and Simulation Tool for River-systems that could be used to explore scenarios. The performance of the model was demonstrated by the reproduction of long-term statistics describing loads and concentrations, together with graphical output in the form of time series and distributions. The simulations were subsequently used to drive a linked catchment-river-estuary-coast-sea model covering the full domain of the RACS area. [Copyright &y& Elsevier]

Background/Importance: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. Objective: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. Evidence Review: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non‐pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. Findings: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy‐induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS‐I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N‐acetyl‐cysteine (2), acetyl‐l‐carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha‐lipoic acid (1), l‐carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha‐lipoic acid (5 studies), vitamin B12 (3), acetyl‐l‐carnitine (3), vitamin E (1), vitamin D (2), and a low‐fat plant‐based diet (1). Vitamin C was studied to treat CRPS‐I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. Conclusions: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N‐acetyl‐cysteine, l‐carnosine, crocin, and magnesium is warranted. Acetyl‐l‐carnitine was found to be likely ineffective or harmful. Alpha‐lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha‐lipoic acid, acetyl‐l‐carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS‐I also seems promising. Further research is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Refractory hypoxemia during veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) may require an additional cannula (VV-V ECMO) to improve oxygenation. This intervention includes risk of recirculation and other various adverse events (AEs) such as injury to the lung, cannula malpositioning, bleeding, circuit or cannula thrombosis requiring intervention (i.e., clot), or cerebral injury. During the study period, 23 of 142 V-V ECMO patients were converted to VV-V utilizing two separate cannulas for bi-caval drainage with an additional upper extremity cannula placed for return. Of those, 21 had COVID-19. In the first 24 h after conversion, ECMO flow rates were higher (5.96 vs 5.24 L/min, p = .002) with no significant change in pump speed (3764 vs 3630 revolutions per minute [RPMs], p = .42). Arterial oxygenation (PaO2) increased (87 vs 64 mmHg, p < .0001) with comparable pre-oxygenator venous saturation (61 vs 53.3, p = .12). By day 5, flows were similar to pre-conversion values at lower pump speed but with improved PaO2. Unadjusted survival was similar in those converted to VV-V ECMO compared to V-V ECMO alone (70% [16/23] vs 66.4% [79/119], p = .77). In a mixed effect regression model, any incidence of AEs, demonstrated a negative impact on PaO2 in the first 48 h but not at day 5. VV-V ECMO improved oxygenation with increasing flows without a significant difference in AEs or pump speed. AEs transiently impacted oxygenation. VV-V ECMO is effective and feasible strategy for refractory hypoxemia on VV-ECMO allowing for higher flow rate and unchanged pump speed. [ABSTRACT FROM AUTHOR]

Climate change increases the occurrence and severity of droughts due to increasing temperatures, altered circulation patterns, and reduced snow occurrence. While Europe has suffered from drought events in the last decade unlike ever seen since the beginning of weather recordings, harmonized long-term datasets across the continent are needed to monitor change and support predictions. Here we present soil moisture data from 66 cosmic-ray neutron sensors (CRNSs) in Europe (COSMOS-Europe for short) covering recent drought events. The CRNS sites are distributed across Europe and cover all major land use types and climate zones in Europe. The raw neutron count data from the CRNS stations were provided by 24 research institutions and processed using state-of-the-art methods. The harmonized processing included correction of the raw neutron counts and a harmonized methodology for the conversion into soil moisture based on available in situ information. In addition, the uncertainty estimate is provided with the dataset, information that is particularly useful for remote sensing and modeling applications. This paper presents the current spatiotemporal coverage of CRNS stations in Europe and describes the protocols for data processing from raw measurements to consistent soil moisture products. The data of the presented COSMOS-Europe network open up a manifold of potential applications for environmental research, such as remote sensing data validation, trend analysis, or model assimilation. The dataset could be of particular importance for the analysis of extreme climatic events at the continental scale. Due its timely relevance in the scope of climate change in the recent years, we demonstrate this potential application with a brief analysis on the spatiotemporal soil moisture variability. The dataset, entitled "Dataset of COSMOS-Europe: A European network of Cosmic-Ray Neutron Soil Moisture Sensors", is shared via Forschungszentrum Jülich: 10.34731/x9s3-kr48 (Bogena and Ney, 2021). [ABSTRACT FROM AUTHOR]

Human-caused climate change increases the occurrence and severity of droughts due to increasing temperatures, altered circulation patterns and reduced snow occurrence. For example, Europe has suffered from drought events in the last decade like never since the beginning of weather recording. Here we present soil moisture data from 65 Cosmic-ray neutron sensors (CRNS) in Europe (COSMOS-Europe for short) covering recent drought events. The CRNS sites are distributed across Europe and cover all major land use types and climate zones in Europe. The raw neutron count data from the CRNS stations were provided by 23 research institutions and processed using state-of-the-art methods. The harmonised processing included correction of the raw neutron counts, and a harmonised methodology for the conversion into soil moisture based on available in-situ information. In addition, information on the data uncertainty is provided with the dataset, information that is particularly useful for remote sensing and modelling applications. This paper presents the current spatiotemporal coverage of CRNS stations in Europe and describes the protocols for data processing from raw measurements to consistent soil moisture products as well as first results on how the recent drought events have been captured by the CRNS network. This harmonised European soil moisture dataset will help both hydrologists and climate scientists to study individual drought events, to understand their causes, to evaluate and improve their modelling, and to estimate the extremity of current events. The dataset, entitled “Dataset of COSMOS-Europe: A European network of Cosmic-Ray Neutron Soil Moisture Sensors”, is shared via Forschungszentrum Jülich: https://doi.org/10.34731/x9s3-kr48 (Bogena and Ney, 2021). [ABSTRACT FROM AUTHOR]

The COSMOS-UK observation network has been providing field-scale soil moisture and hydrometeorological measurements across the UK since 2013. At the time of publication a total of 51 COSMOS-UK sites have been established, each delivering high-temporal resolution data in near-real time. Each site utilizes a cosmic-ray neutron sensor, which counts epithermal neutrons at the land surface. These measurements are used to derive field-scale near-surface soil water content, which can provide unique insight for science, industry, and agriculture by filling a scale gap between localized point soil moisture and large-scale satellite soil moisture datasets. Additional soil physics and meteorological measurements are made by the COSMOS-UK network including precipitation, air temperature, relative humidity, barometric pressure, soil heat flux, wind speed and direction, and components of incoming and outgoing radiation. These near-real-time observational data can be used to improve the performance of hydrological models, validate remote sensing products, improve hydro-meteorological forecasting, and underpin applications across a range of other scientific fields. The most recent version of the COSMOS-UK dataset is publically available at 10.5285/b5c190e4-e35d-40ea-8fbe-598da03a1185 (Stanley et al., 2021). [ABSTRACT FROM AUTHOR]

Targeted overexpression of an ornithine decarboxylase (ODC) transgene to mouse skin (the K6/ ODC mouse) significantly enhances susceptibility to carcinogenesis. While in most strain backgrounds the predominant tumor type resulting from initiation-promotion protocols is benign squamous papilloma, K6/ODC mice on a FVB/N background develop malignant squamous cell carcinomas (SCCs) rapidly and in high multiplicity after carcinogen treatment. We have investigated the utility of polyamine-based therapy against SCCs in this model using the ODC inhibitor 2- difluoromethylornithine delivered orally. At a 2% concentration in drinking water, DFMO caused rapid tumor regression, but in most cases, tumors eventually regrew rapidly even in the presence of DFMO. The tumors that regrew were spindle cell carcinomas, an aggressive undifferentiated variant of SCC. At 1% DFMO in the drinking water, tumors also responded rapidly, but tumor regrowth did not occur. The majority of DFMO-treated SCCs were classified as complete responses, and in some cases, apparent tumor cures were achieved. The enzymatic activity of ODC, the target of DFMO, was substantially reduced after treatment with 1% DFMO and the high SCC polyamine levels, especially putrescine, were also significantly lowered. Based on the results of BrdUrd labeling and TUNEL assays, the effect of DFMO on SCC growth was accompanied by a significant reduction in tumor proliferation with no increase in the apoptotic index. These results demonstrate that SCCs, at least in the mouse, are particularly sensitive to polyamine-based therapy. [ABSTRACT FROM AUTHOR]

The COSMOS-UK observation network has been providing field scale soil moisture and hydrometeorological measurements across the UK since 2013. At the time of publication a total of 51 COSMOS-UK sites have been established, each delivering high temporal resolution data in near-real time. Each site utilises a cosmic-ray neutron sensor, which counts fast neutrons at the land surface. These measurements are used to derive field scale near-surface soil water content, which can provide unique insight for science, industry, and agriculture by filling a scale gap between localised point soil moisture and large-scale satellite soil moisture datasets. Additional soil physics and meteorological measurements are made by the COSMOS-UK network including precipitation, air temperature, relative humidity, barometric pressure, soil heat flux, wind speed and direction, and components of incoming and outgoing radiation. These near-real time observational data can be used to improve the performance of hydrological models, validate remote sensing products, improve hydro-meteorological forecasting and underpin applications across a range of other scientific fields. The most recent version of the COSMOS-UK dataset is publically available at https://doi.org/10.5285/37702a54-b7a4-40ff-b62e-d14b161b69ca (Stanley et al., 2020). [ABSTRACT FROM AUTHOR]

Objective. We aim to study the impact of preoperative opioid dosage on postoperative length of stay (LOS) in patients undergoing thoracic spinal cord stimulator (SCS) placement surgery as a primary objective. Secondary objectives of this study include investigating patient-controlled analgesia (PCA) usage and postoperative complications like fever in relation to patients' preoperative opioid dosage and postoperative LOS. Methods. A total of 47 patients who underwent thoracic SCS for first time were retrospectively studied through chart review. These patients were categorized into two groups, with Group I patients taking a morphine equivalent dose (MED) of less than 100mg and Group II patients taking an MED of more than 100mg preoperatively. Results. Group I had 22 patients, and Group II had 25 patients. The average age in Group I was 53.45 years, and the average age in Group II was 50.16 years. There were seven males (38%) and 15 females (62%) in Group I, and in Group II there were 11 males (44%) and 14 females (56%). The average LOS in both groups was two days. In Group I, there were 16 patients (73%) who had an LOS of one day and six patients (27%) who had an LOS of more than one day, and in Group II there were 11 patients (44%) who had an LOS of less than one day and 14 patients (56%) who had an LOS of more than one day, with a P value of 0.047. On univariate analysis, postoperative fever and PCA usage correlated with longer hospital stay, with a P value of < 0.001. Conclusion. Patients on high-dose chronic opioid therapy, defined as an MED greater than 100 mg, who undergo thoracic spinal cord stimulator surgery tend to have longer postoperative hospital stays compared with patients on lower-dose opioid therapy. [ABSTRACT FROM AUTHOR]

This paper describes the development of the first operational seasonal hydrological forecasting service for the UK, the Hydrological Outlook UK (HOUK). Since June 2013, this service has delivered monthly forecasts of streamflow and groundwater levels, with an emphasis on forecasting hydrological conditions over the next three months, accompanied by outlooks over longer time horizons. This system is based on three complementary approaches combined to produce the outlooks: (i) national-scale modelling of streamflow and groundwater levels based on dynamic seasonal rainfall forecasts, (ii) catchment-scale modelling where streamflow and groundwater level models are driven by historical meteorological forcings (i.e. the Ensemble Streamflow Prediction, ESP, approach), and (iii) a catchment-scale statistical method based on persistence and historical analogues. This paper provides the background to the Hydrological Outlook, describes the various component methods in detail and then considers the impact and usefulness of the product. As an example of a multi-method, operational seasonal hydrological forecasting system, it is hoped that this overview provides useful information and context for other forecasting initiatives around the world. [ABSTRACT FROM AUTHOR]

Objective Intracranial monitoring is fundamental to epilepsy surgery, with reported complication rates of 3-17%. We aimed to assess the differences in complication rates between subdural and depth electrodes. Methods We conducted a retrospective review of 317 electrode implantation procedures. All documented abnormal postoperative findings were recorded in our study. Those that resulted in a significant alteration of treatment course, including neurologic deficit, long-term medication use, reoperation, or hospital readmission, were deemed clinically significant. When possible, findings were attributed to a particular electrode type based on relative location to each electrode. Results Postoperative abnormalities were associated with SDE placement in 152 (47.9%) procedures and 40 (25.2%) DE placements (p < 0.001). Twenty-nine (9.1%) clinically significant complications were seen in the subdural electrode ( SDE) group compared to 10 associated with DEs (6.3%, p = 0.37). SDEs were associated with increased rates of any postoperative hemorrhage (p < 0.001) or extraaxial collection (p = 0.007). Subdural grid placement was associated with an increased risk of any extraaxial collection (odds ratio [ OR 2.42), as well as clinically significant collections ( OR 9.47). Previous craniotomy was found to be associated with any abnormal postoperative finding ( OR 1.71) as well as radiographic hemorrhage ( OR 1.99). Concurrent resection is also associated with abnormal findings ( OR 1.83) and extraaxial collections ( OR 2.37). The overall complication rate was 9.1%, with 13 procedures (4.1%) resulting in neurologic deficit. However, only two patients (0.6%) had permanent neurologic sequelae resulting from lead placement. Significance Subdural electrodes appear to have an increased rate of abnormal postoperative findings, including hemorrhage and extraaxial collections; however, there was no difference in clinically significant findings. Subdural grids also appear to be associated with symptomatic extraaxial collections, and previous craniotomy increases the risk of hemorrhage. Overall, intracranial monitoring remains a safe and effective procedure for localization of operative seizure foci. Patient selection and risk education for various modalities is an essential aspect of preoperative evaluation. [ABSTRACT FROM AUTHOR]

Most sporadic colon adenomas acquire mutations in the adenomatous polyposis coli gene (APC) and show defects in APC-dependent signaling. APC influences the expression of several genes, including the c-myc oncogene and its antagonist Mad1. Ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is a transcriptional target of c-myc and a modifier of APC-dependent tumorigenesis. A single-nucleotide polymorphism exists in intron 1 of the human ODC gene, which lies between two myc-binding domains. This region is known to affect ODC transcription, but no data exist on the relationship of this polymorphism to risk of colorectal neoplasia in humans. We show that individuals homozygous for the minor ODC A-allele who reported using aspirin are ≈0.10 times as likely to have an adenoma recurrence as non-aspirin users homozygous for the major G-allele. Mad1 selectively suppressed the activity of the ODC promoter containing the A-allele, but not the G-allele, in a human colon cancer-derived cell line (HT29). Aspirin (≥10 µM) did not affect ODC allele-specific promoter activity but did activate polyamine catabolism and lower polyamine content in HT29 cells. We propose that the ODC polymorphism and aspirin act independently to reduce the risk of adenoma recurrence by suppressing synthesis and activating catabolism, respectively, of colonic mucosal polyamines. These findings confirm the hypothesis that the ODC polymorphism is a genetic marker for colon cancer risk, and support the use of ODC inhibitors and aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs), in combination as a strategy for colon cancer prevention. [ABSTRACT FROM AUTHOR]

Objective: To determine the rate of change of antimüllerian hormone (AMH) level in the late reproductive years and its associations with time to menopause (TTM). We hypothesized that the rate of change between two measures of AMH reflects follicular atresia and varies among women independent of age.Design: A14-year follow-up.Setting: A randomly identified, population-based cohort (Penn Ovarian Aging Study).Patient(s): Two measures of AMH were evaluated in survival analysis of 293 women.Intervention(s): None.Main Outcome Measure(s): Time to menopause.Result(s): The rate of AMH change was a strong independent predictor of TTM in multivariable analysis after adjusting for AMH baseline, age, and smoking (hazard ratio for 1 SD change = 1.82, 95% confidence interval 1.56-2.14). Among women with similar AMH levels, TTM differed by approximately 2 years when compared between a slow and fast rate of AMH change. A significant interaction of AMH rate of change and age indicated that a faster decrease in AMH level was associated with an increased risk of menopause in women aged 35-39 years (hazard ratio 6.97, 95% confidence interval 3.81-12.72), with less dramatic but significant associations in women aged 40-44 and 45-48 years.Conclusion(s): The AMH rate of change was independently associated with TTM in late reproductive-age women and increased the precision of estimates of TTM when included with an AMH baseline level and age. The rate of AMH change may be a more direct surrogate than age and increases the precision of estimates of TTM during this clinically important time period. [ABSTRACT FROM AUTHOR]

Objective: To determine the rate of change of antimüllerian hormone (AMH) level in the late reproductive years and its associations with time to menopause (TTM). We hypothesized that the rate of change between two measures of AMH reflects follicular atresia and varies among women independent of age. Design: A14-year follow-up. Setting: A randomly identified, population-based cohort (Penn Ovarian Aging Study). Patient(s): Two measures of AMH were evaluated in survival analysis of 293 women. Intervention(s): None. Main Outcome Measure(s): Time to menopause. Result(s): The rate of AMH change was a strong independent predictor of TTM in multivariable analysis after adjusting for AMH baseline, age, and smoking (hazard ratio for 1 SD change = 1.82, 95% confidence interval 1.56–2.14). Among women with similar AMH levels, TTM differed by approximately 2 years when compared between a slow and fast rate of AMH change. A significant interaction of AMH rate of change and age indicated that a faster decrease in AMH level was associated with an increased risk of menopause in women aged 35–39 years (hazard ratio 6.97, 95% confidence interval 3.81–12.72), with less dramatic but significant associations in women aged 40–44 and 45–48 years. Conclusion(s): The AMH rate of change was independently associated with TTM in late reproductive-age women and increased the precision of estimates of TTM when included with an AMH baseline level and age. The rate of AMH change may be a more direct surrogate than age and increases the precision of estimates of TTM during this clinically important time period. [ABSTRACT FROM AUTHOR]