Using remote sensing to assess peatland resilience by estimating soil surface moisture and drought recovery.

Peatland areas provide a range of ecosystem services, including biodiversity, carbon storage, clean water, and flood mitigation, but many areas of peatland in the UK have been degraded through human land use including drainage. Here, we explore whether remote sensing can be used to monitor peatland resilience to drought. We take resilience to mean the rate at which a system recovers from perturbation; here measured literally as a recovery timescale of a soil surface moisture proxy from drought lowering. Our objectives were (1) to assess the reliability of Sentinel-1 Synthetic Aperture Radar (SAR) backscatter as a proxy for water table depth (WTD); (2) to develop a method using SAR to estimate below-ground (hydrological) resilience of peatlands; and (3) to apply the developed method to different sites and consider the links between resilience and land management. Our inferences of WTD from Sentinel-1 SAR data gave results with an average Pearson's correlation of 0.77 when compared to measured WTD values. The 2018 summer drought was used to assess resilience across three different UK peatland areas (Dartmoor, the Peak District, and the Flow Country) by considering the timescale of the soil moisture proxy recovery. Results show clear areas of lower resilience within all three study sites, which often correspond to areas of high drainage and may be particularly vulnerable to increasing drought severity/events under climate change. This method is applicable to monitoring peatland resilience elsewhere over larger scales, and could be used to target restoration work towards the most vulnerable areas.

Predicting 30-day mortality after hip fracture surgery: Evaluation of the National Hip Fracture Database case-mix adjustment model.

OBJECTIVES: The National Hip Fracture Database (NHFD) publishes hospital-level risk-adjusted mortality rates following hip fracture surgery in England, Wales and Northern Ireland. The performance of the risk model used by the NHFD was compared with the widely-used Nottingham Hip Fracture Score. METHODS: Data from 94 hospitals on patients aged 60 to 110 who had hip fracture surgery between May 2013 and July 2013 were analysed. Data were linked to the Office for National Statistics (ONS) death register to calculate the 30-day mortality rate. Risk of death was predicted for each patient using the NHFD and Nottingham models in a development dataset using logistic regression to define the models' coefficients. This was followed by testing the performance of these refined models in a second validation dataset. RESULTS: The 30-day mortality rate was 5.36% in the validation dataset (n = 3861), slightly lower than the 6.40% in the development dataset (n = 4044). The NHFD and Nottingham models showed a slightly lower discrimination in the validation dataset compared with the development dataset, but both still displayed moderate discriminative power (c-statistic for NHFD = 0.71, 95% confidence interval (CI) 0.67 to 0.74; Nottingham model = 0.70, 95% CI 0.68 to 0.75). Both models defined similar ranges of predicted mortality risk (1% to 18%) in assessment of calibration. CONCLUSIONS: Both models have limitations in predicting mortality for individual patients after hip fracture surgery, but the NHFD risk adjustment model performed as well as the widely-used Nottingham prognostic tool and is therefore a reasonable alternative for risk adjustment in the United Kingdom hip fracture population.Cite this article: Bone Joint Res 2017;6:550-556.

Understanding mortality rates after hip fracture repair using ASA physical status in the National Hip Fracture Database.

Hip fracture is the most common reason for older patients to need emergency anaesthesia and surgery. Up to one-third of patients die in the year after hip fracture, but this view of outcome may encourage therapeutic nihilism in peri-operative decisions and discussions. We used a multicentre national dataset to examine relative and absolute mortality rates for patients presenting with hip fracture, stratified by ASA physical status. We analysed ASA physical status, dates of surgery, death and hospital discharge for 59,369 out of 64,864 patients in the 2015 National Hip Fracture Database; 3914 (6.6%) of whom died in hospital. Rates of death in hospital were 1.8% in ASA 1-2 patients compared with 16.5% in ASA 4 patients. Survival rates for ASA 4 patients on each of the first three postoperative days were: 98.8%, 99.1% and 99.1% (compared with figures of > 99.9% in ASA 1-2 patients over these days). Survival on postoperative day 6 was 99.4% for ASA 4 patients. Nearly half (48.6%) of the 1427 patients who did not have surgery died in hospital. Although technically sound, a focus on cumulative and relative risk of mortality may frame discussions in an unduly negative fashion, discouraging surgeons and anaesthetists from offering an operation, and deterring patients and their loved ones from agreeing to it. A more optimistic and pragmatic explanation that over 98% of ASA 4 patients survive both the day of surgery and the day after it, may be more appropriate.

Large-displacement, hydrothermal frictional properties of DFDP-1 fault rocks, Alpine Fault, New Zealand: Implications for deep rupture propagation.

The Alpine Fault, New Zealand, is a major plate-bounding fault that accommodates 65-75% of the total relative motion between the Australian and Pacific plates. Here we present data on the hydrothermal frictional properties of Alpine Fault rocks that surround the principal slip zones (PSZ) of the Alpine Fault and those comprising the PSZ itself. The samples were retrieved from relatively shallow depths during phase 1 of the Deep Fault Drilling Project (DFDP-1) at Gaunt Creek. Simulated fault gouges were sheared at temperatures of 25, 150, 300, 450, and 600°C in order to determine the friction coefficient as well as the velocity dependence of friction. Friction remains more or less constant with changes in temperature, but a transition from velocity-strengthening behavior to velocity-weakening behavior occurs at a temperature of T = 150°C. The transition depends on the absolute value of sliding velocity as well as temperature, with the velocity-weakening region restricted to higher velocity for higher temperatures. Friction was substantially lower for low-velocity shearing (V < 0.3 µm/s) at 600°C, but no transition to normal stress independence was observed. In the framework of rate-and-state friction, earthquake nucleation is most likely at an intermediate temperature of T = 300°C. The velocity-strengthening nature of the Alpine Fault rocks at higher temperatures may pose a barrier for rupture propagation to deeper levels, limiting the possible depth extent of large earthquakes. Our results highlight the importance of strain rate in controlling frictional behavior under conditions spanning the classical brittle-plastic transition for quartzofeldspathic compositions.

Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).

We re-analysed prospective data collected by anaesthetists in the Anaesthesia Sprint Audit of Practice (ASAP-1) to describe associations with linked outcome data. Mortality was 165/11,085 (1.5%) 5 days and 563/11,085 (5.1%) 30 days after surgery and was not associated with anaesthetic technique (general vs. spinal, with or without peripheral nerve blockade). The risk of death increased as blood pressure fell: the odds ratio (95% CI) for mortality within five days after surgery was 0.983 (0.973-0.994) for each 5 mmHg intra-operative increment in systolic blood pressure, p = 0.0016, and 0.980 (0.967-0.993) for each mmHg increment in mean pressure, p = 0.0039. The equivalent odds ratios (95% CI) for 30-day mortality were 0.968 (0.951-0.985), p = 0.0003 and 0.976 (0.964-0.988), p = 0.0001, respectively. The lowest systolic blood pressure after intrathecal local anaesthetic relative to before induction was weakly correlated with a higher volume of subarachnoid bupivacaine: r(2) -0.10 and -0.16 for hyperbaric and isobaric bupivacaine, respectively. A mean 20% relative fall in systolic blood pressure correlated with an administered volume of 1.44 ml hyperbaric bupivacaine. Future research should focus on refining standardised anaesthesia towards administering lower doses of spinal (and general) anaesthesia and maintaining normotension.

The influence of socioeconomic status on the incidence, outcome and mortality of fractures of the hip.

This is the first study to use the English Indices of Multiple Deprivation 2007, the Government's official measure of multiple deprivation, to analyse the effect of socioeconomic status on the incidence of fractures of the hip and their outcome and mortality. Our sample consisted of all patients admitted to hospital with a fracture of the hip (n = 7511) in Nottingham between 1999 and 2009. The incidence was 1.3 times higher (p = 0.038) in the most deprived populations than in the least deprived; the most deprived suffered a fracture, on average, 1.1 years earlier (82.0 years versus 83.1 years, p < 0.001). The mortality rate proved to be significantly higher in the most deprived population (log-rank test, p = 0.033), who also had a higher number of comorbidities (p = 0.001). This study has shown an increase in the incidence of fracture of the hip in the most deprived population, but no association between socioeconomic status and mortality at 30 days. Preventative programmes aimed at reducing the risk of hip fracture should be targeted towards the more deprived if they are to make a substantial impact.

Judet decortication and compression plate fixation of long bone non-union: Is bone graft necessary?

Non-union occurs in 5-10% of all fractures and is caused by a variety of mechanical and biological factors. Stable fixation is essential and many authors recommend the addition of bone graft. Our aim was to evaluate the results of internal fixation using Judet decortication and compression plating for long bone fractures and assess the impact of bone grafting on union rates. Our study group comprised all the patients undergoing compression plate fixation under a single surgeon over a fourteen year period (n=96). AO principles were used and the standard technique involved Judet decortication, compression plating and lag screws. Autologous bone graft was harvested from the iliac crest. The mean age was 45 years and 62% were male. The fracture site was the clavicle (n=20); humerus (n=23); radius and ulna (n=5); femur (n=31) and tibia (n=17). The primary fracture treatment was non-operative (n=41); IM nail (n=22); plate fixation (n=28) and external fixation (n=5). Deep infection was present in 6 cases. Bone graft was used in 40 cases. 91/96 non-unions treated with compression plating healed (95%). Bone grafting was used in all cases for the initial part of the series but its use declined as the surgeon became more confident that the non-unions would heal without the use of bone graft. The case mix and complexity remained constant throughout the study period and the union rate also remained constant. The mean time to radiological union was 6.4 months. In those treated with a compression plate without bone graft the union rate was 94.6% whilst the addition of bone graft resulted in a union rate of 95% (p=0.67). From our study we concluded that the routine use of autologous bone graft may not be necessary and, based upon the union rates observed in this study, a prospective randomised study to evaluate the use of bone graft in non-union surgery would need a sample size of 194,000 to detect a significant increase in union with 80% power. In terms of Numbers Needed Treat (NNT), we would need to give 1179 patients a bone graft to prevent one additional failure of healing.

Epidemiology and outcome of fracture of the hip in women aged 65 years and under: a cohort study.

We examined prospectively collected data from 6782 consecutive hip fractures and identified 327 fractures in 315 women aged ≤65 years. We report on their demographic characteristics, treatment and outcome and compare them with a cohort of 4810 hip fractures in 4542 women aged > 65 years. The first significant increase in age-related incidence of hip fracture was at 45, rather than 50, which is when screening by the osteoporosis service starts in most health areas. Hip fractures in younger women are sustained by a population at risk as a result of underlying disease. Mortality of younger women with hip fracture was 46 times the background mortality of the female population. Smoking had a strong influence on the relative risk of 'early' (≤ 65 years of age) fracture. Lag screw fixation was the most common method of operative treatment. General complication rates were low, as were re-operation rates for cemented prostheses. Kaplan-Meier implant survivorship of displaced intracapsular fractures treated by reduction and lag screw fixation was 71% (95% confidence interval 56 to 81) at five years. The best form of treatment remains controversial.

Ward-based rather than team-based junior surgical doctors reduce mortality for patients with a fracture of the proximal femur: results from a two-year observational study.

We performed a retrospective study of a departmental database to assess the efficacy of a new model of orthopaedic care on the outcome of patients with a fracture of the proximal femur. All 1578 patients admitted to a university teaching hospital with a fracture of the proximal femur between December 2007 and December 2009 were included. The allocation of Foundation doctors years 1 and 2 was restructured from individual teams covering several wards to pairs covering individual wards. No alterations were made in the numbers of doctors, their hours, out-of-hours cover, or any other aspect of standard patient care. Outcome measures comprised 30-day mortality and cause, complications and length of stay. Mortality was reduced from 11.7% to 7.6% (p = 0.007, Cox's regression analysis); adjusted odds ratio was 1.559 (95% confidence interval 1.128 to 2.156). Reductions were seen in Clostridium difficile colitis (p = 0.017), deep wound infection (p = 0.043) and gastrointestinal haemorrhage (p = 0.033). There were no differences in any patient risk factors (except the prevalence of chronic obstructive pulmonary disease), cause of death and length of stay before and after intervention. The underlying mechanisms are unclear, but may include improved efficiency and medical contact time. These findings may have implications for all specialties caring for patients on several wards, and we believe they justify a prospective trial to further assess this effect.

What is the financial cost of treating periprosthetic hip fractures?

A total of 146 patients were identified from a prospective database of all hip fractures over a 10-year period at a United Kingdom teaching hospital. The financial costs were calculated and analysed and then compared with the money recovered through the tariff produced by Payment by Results.A total of 62% of the study group were female; mean age of 79 years; mean length of stay of 39 days.Fractures occurred around total hip replacement (THR) in 63 cases, revision THR in 27 cases and hemiarthroplasty in 56 cases. Fixation of the fracture was performed in 61 cases, revision arthroplasty in 62 cases and 23 were treated non-operatively.The mean cost of treatment was £23,469 per patient (range £615­£223,000; median £18,031). Ward costs were responsible for 80.3%, theatre costs 5.7%, implants 6.7% and investigations 7.3%. The difference in cost was statistically significant when further surgery was required (p = 0.01) and length of stay was greater than 30 days (p < 0.0001), and when compared with the money recovered by the Trust(mean £3702; p < 0.0001). These results reveal the significant economic impact of treating this group of patients at specialist centres.

Hip fracture audit: the Nottingham experience.

The hip fracture audit in Nottingham started in May 1999. Using our data, we have developed the Nottingham Hip Fracture score and are able to predict long-term survival. High quality data collection is best achieved by trained staff dedicated to data collection and analysis. We have found it very cost-effective to train audit clerks in basic data analysis and statistical techniques, allowing for rapid analysis of data. We have developed a pre-operative scoring system to predict 30-day mortality for patients undergoing hip fracture surgery and the score is calculated for all patients over 65 years. In 2008, our audit data were used to assess mortality associated with hip fractures in the geriatric population at 5 years, and to identify the influence of pre-operative age, cognitive state, mobility and residential status on long-term survival. This study allows us to identify patients with a higher chance of long-term survival and consider surgical management that may provide a better long-term outcome. The prevalence of hip fracture in our population has steadily increased over the past decade and we are able to report a fall in the 30-day mortality and the 1-year mortality with time. Using the Nottingham Hip Fracture score which identifies patients pre-operatively that are at high risk of mortality has proved extremely useful in clinical practise. The United Kingdom National Hip Fracture Database was established in 2007 to improve the quality and cost-effectiveness of care for hip fracture patients. Variation in quality of care should be reduced between units and best practise adopted throughout the health service.

Age-specific incidence of first and second fractures of the hip.

We determined the age-specific incidence of a second fracture of the hip and compared it with that of a primary fracture in a study population drawn from 6331 patients admitted to Nottingham University Hospital with a primary fracture of the hip over a period of 8.5 years. The incidence of a second fracture was determined using survival analysis. The mean age-specific incidence rates of primary hip fracture were calculated using census data. The overall incidence of a second fracture was 2.7% at one year and 7.8% at 8.5 years. That of a primary fracture was 50 per 100 000 in women aged 55 to 64 years rising to 3760 in those aged 84 years and over. The incidence of a second fracture in women aged 55 to 64 years was 2344 per 100 000. Patients of this age had a relative risk of 45 (95% confidence interval 13 to 155) for further fracture when compared with the population at risk of a first fracture. The incidence of a second fracture in women aged > 84 years was 2451 per 100 000 (relative risk 0.7, 95% confidence interval 0.5 to 0.9). A similar trend was seen in men. Patients sustaining a primary fracture of the hip between the ages of 55 and 64 years have a much greater risk of further fracture than the normal population, whereas those over 84 years have a similar risk. These findings have important implications for the provision of fracture prevention services in primary and secondary care.

Metatarsal fractures and sports.

OBJECTIVES: Metatarsal fractures are commonly sustained during sport but little is written about metatarsal fractures in the athletic population. Demographics and definitive treatment in patients who sustained metatarsal fractures through sport were compared with an overall metatarsal fracture population. MATERIALS AND METHODS: We used a prospective cohort study from a teaching hospital fracture clinic. Eighteen months of data were coded from presentation with a metatarsal fracture. Demographics, metatarsal fracture, participating sport and treatment were recorded and analysed. RESULTS: 791 patients presented with metatarsal fractures in an 18 month period with 74 metatarsal fractures sustained through sport. In the overall cohort group, there were 443 females and 348 males with a mean age of 44 (age range 15-91) and in the athletic population there were 6 females and 68 males with a mean age of 26 (age range 15-62). The majority of the metatarsal fractures sustained from sport were from soccer (73%), with the fifth metatarsal being the most commonly fractured. The definitive treatment in both groups appears to be similar, where the mainstay of treatment is conservative with the use of cast or early mobilisation with an elasticated support stocking. CONCLUSION: In this cohort approximately 9% of metatarsal fractures were sustained through sport, with soccer being the most common sport. Following high profile injuries to metatarsals in soccer players, it has been suggested that the incidence of these fractures is rising. Thus, it is recommended that a detailed prospective study be undertaken to specifically study the incidence, aetiology and morbidity of metatarsal fractures in the athletic population.

Hip fractures after falls in hospital: a retrospective observational cohort study.

OBJECTIVES: To compare the prevalence and characteristics of hip fractures sustained after inpatient falls (hospital subgroup) to those presenting with a fall in the community (control group). DESIGN: Retrospective observational cohort study. SETTING: University teaching hospital. PARTICIPANTS: 5879 hip fractures occurred over an 8-year period, 327 of these took place after a fall as a hospital inpatient. OUTCOME MEASURES: Comparison of 30-day and 1 year mortality, co-morbidities, length of post-fracture hospital stay, specific complication rates and cognitive function between the hospital and control group. Other specific data on those falling in hospital was also collected. RESULTS: There were significantly higher rates (p<0.001) of cerebrovascular, chronic obstructive airways and renal disease, diabetes, malignancy and polypharmacy in patients suffering falls in hospital. Mini-mental test scores (MTS) were also significantly reduced in this subgroup (p<0.001). 30-day and 1 year mortality rates were 9% and 26%, respectively in the control group and almost double this in the hospital subgroup, being 18% and 47%, respectively (30 days, 95% CI 2.00 (1.54-2.60): p<0.001; 1 year, 95% CI 2.04 (1.73-2.40): p<0.001). There was no statistical difference between post-operative complications or length of stay post-fracture. 55% of falls in hospital took place on medical/geriatric wards with an additional 14% occurring on psychiatric units. DISCUSSION: Patients suffering hip fractures after falls in hospital are frailer with impaired cognitive function and have more co-morbidities than those suffering a fracture in the community. These patients have increased mortality, with almost 50% dead within 1 year of the fall. The majority of hip fractures after falls occur in medical or geriatric wards, but the highest risk group appears to be elderly patients on psychiatric wards. Therefore, falls risk assessment and falls prevention schemes in hospital elderly patients are of paramount importance.

Early infection after hip fracture surgery: risk factors, costs and outcome.

Prospective data on hip fracture from 3686 patients at a United Kingdom teaching hospital were analysed to investigate the risk factors, financial costs and outcomes associated with deep or superficial wound infections after hip fracture surgery. In 1.2% (41) of patients a deep wound infection developed, and 1.1% (39) had a superficial wound infection. A total of 57 of 80 infections (71.3%) were due to Staphylococcus aureus and 39 (48.8%) were due to MRSA. No statistically significant pre-operative risk factors were detected. Length of stay, cost of treatment and pre-discharge mortality all significantly increased with deep wound infection. The one-year mortality was 30%, and this increased to 50% in those who developed an infection (p < 0.001). A deep infection resulted in doubled operative costs, tripled investigation costs and quadrupled ward costs. MRSA infection increased costs, length of stay, and pre-discharge mortality compared with non-MRSA infection.

Mortality and causes of death among patients with isolated limb and pelvic fractures.

Between May 2001 and May 2005, all 8834 adults admitted to our hospital with fractures to the limbs and pelvis were prospectively entered onto a database. Information was cross-referenced with the Office of National Statistics, and all patients who died during the study period were identified. Mortality rates were adjusted for age, gender and type of injury and cause of death was identified from hospital records. Neck of femur fractures accounted for 32% of admissions. Younger patients were more likely to be male and older patients more likely to be female. Overall 30-day and 1-year mortalities were 4.5 and 13%, respectively. Increased mortality was associated with age, male gender and fractures of the femur or pelvis.

Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories.

Recent studies of human oocytes have demonstrated an enrichment for distal exchanges among meiosis I (MI) nondisjunction events and for proximal exchanges among meiosis II (MII) events. Our characterization of 103 cases of spontaneous X chromosome nondisjunction in Drosophila oocytes strongly parallels these observations. The recombinational histories of MI (97/103) and MII (6/103) nondisjunctional ova were strikingly different. MI nondisjunction occurred primarily in oocytes with non-exchange X chromosomes; of the new nondisjoining exchange bivalents, most carried distal crossovers. Thus, spontaneous MI nondisjunction reflects the failure of the achiasmate segregation systems. MII nondisjunction occurred only in oocytes with proximal exchanges. We propose several models to explain how very proximal exchanges might impair proper segregation.

Strain-dependent variation in the NADH-dependent diacetyl reductase activities of larger- and alebrewing yeasts.

Significant differences were observed in the zymogram patterns of NAD(+)-dependent ethanol dehydrogenase and acetoin dehydrogenase activity in seven strains of brewer's yeast examined by non-denaturing PAGE. Bottom-fermenting (lager) strains contained quite different activity bands of acetoin dehydrogenase activity compared with top-fermenting (ale) strains. These differences were confirmed when cell-free extracts of ale yeasts were heated at 55 degrees C. This destroyed most of the diacetyl reductase activity, while leaving acetaldehyde reductase and other reductase activities unaffected. In contrast, heating cell-free extracts of lager yeasts at 55 degrees C inactivated diacetyl reductase activity and the other reductase activities at the same rate, and more slowly than with ale strains. Similar distinctions between the two types of yeast could be made by examining the effect of heat on the ratio (activity of the various substrates with NADH as electron donor)/(activity with reduced acetylpyridine-adenine dinucleotide as electron donor). The data show that the acetoin dehydrogenase/diacetyl reductase enzyme present in ale-yeast strains differs in mobility and heat-stability from that of larger strains, and that both can be distinguished from the major alcohol dehydrogenase activity bands.

Nitric oxide-dependent long-term potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase.

The diffusible second messenger, nitric oxide, is synthesised in central neurons in response to activation of glutamate receptors or other stimuli that increase cytosolic Ca2+ concentrations. Among the many roles suggested for nitric oxide in the central nervous system is that of mediating synaptic plasticity. For example, long-term potentiation in the CA1 region of the rat hippocampus was reported to be blocked by inhibitors of nitric oxide synthase and exogenous nitric oxide has been claimed to induce an enduring enhancement of synaptic strength under certain conditions. These findings, however, are controversial and even when a participation of nitric oxide is evident, the transduction mechanism is unclear. A well-known action of nitric oxide is to stimulate the soluble form of guanylyl cyclase, thereby evoking an accumulation of cyclic GMP in target cells but several other mechanisms have been proposed, including stimulation of ADP ribosyltransferase or cyclooxygenase, and nitrosylation of protein thiol residues. The identification of a selective inhibitor of soluble guanylyl cyclase, the oxadiazoloquinoxaline derivative, ODQ, provides, for the first time, the means to investigate the importance of the cyclic GMP pathway in nitric oxide signal transduction. We find that ODQ and the nitric oxide synthase inhibitor, nitroarginine, reduce hippocampal long-term potentiation in an equal and mutually exclusive manner, suggesting that the actions of nitric oxide in this phenomenon are entirely mediated through cyclic GMP. The experiments also show that there is a component of long-term potentiation that involves neither nitric oxide nor cyclic GMP.

Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one.

In brain and other tissues, nitric oxide (NO) operates as a diffusible second messenger that stimulates the soluble form of the guanylyl cylase enzyme and so elicits an accumulation of cGMP in target cells. Inhibitors of NO synthesis have been used to implicate NO in a wide spectrum of physiological and pathophysiological mechanisms in the nervous system and elsewhere. The function of cGMP in most tissues, however, has remained obscure. We have now identified a compound, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), that potently and selectively inhibits NO-stimulated guanylyl cyclase activity. In incubated slices of cerebellum, ODQ reversibly inhibited the NO-dependent cGMP response to glutamate receptor agonists (IC50 approximately nM) but did not affect NO synthase activity. The compound did not affect synaptic glutamate receptor function, as assessed in hippocampal slices, nor did it chemically inactivate NO. ODQ did, however, potentially inhibit cGMP generation in response to NO-donating compounds. An action on NO-stimulated soluble guanylyl cyclase was confirmed in studies with the purified enzyme. ODQ failed to inhibit NO-mediated macrophage toxicity, a phenomenon that is unrelated to cGMP, nor did it affect the activity of particulate guanylyl cyclase or adenylyl cyclase. ODQ is the first inhibitor that acts selectively at the level of a physiological NO "receptor" and, as such, it is likely to prove useful for investigating the function of the cGMP pathway in NO signal transduction.