Southeast Asian Dipterocarp origin and diversification driven by Africa-India floristic interchange.

The evolution and diversification of ancient megathermal angiosperm lineages with Africa-India origins in Asian tropical forests is poorly understood because of the lack of reliable fossils. Our palaeobiogeographical analysis of pollen fossils from Africa and India combined with molecular data and fossil amber records suggest a tropical-African origin of Dipterocarpaceae during the mid-Cretaceous and its dispersal to India during the Late Maastrichtian and Paleocene, leading to range expansion of aseasonal dipterocarps on the Indian Plate. The India-Asia collision further facilitated the dispersal of dipterocarps from India to similar climatic zones in Southeast Asia, which supports their out-of-India migration. The dispersal pathway suggested for Dipterocarpaceae may provide a framework for an alternative biogeographic hypothesis for several megathermal angiosperm families that are presently widely distributed in Southeast Asia.

Complex Foot Infection Treated With Surgical Debridement and Antibiotic Loaded Calcium Sulfate-A Retrospective Cohort Study of 137 Cases.

Complex foot infections involving bone and soft tissue in patients with co-morbidities such as diabetes and peripheral arterial disease (PAD) are a cause of significant hospital admission. They are associated with substantial economic costs to health services worldwide. Historically, severe foot infection has been treated with surgical debridement and prolonged courses of systemic antibiotics. Prolonged systemic antibiotic use increases the risk of drug side effects, antimicrobial resistance and Clostridium difficile infection. The purpose of this study was to investigate whether surgical debridement and implantation of antibiotic loaded calcium sulfate is effective in the resolution of foot infection and wound healing. A retrospective cohort study of 137 consecutive cases of osteomyelitis (127) or significant soft tissue infection (10) over 62 months from 02/2013 to 04/2018 was conducted following local ethical approval. All cases of infection were treated with surgical debridement and local antibiotic-loaded calcium sulfate. The primary outcomes of infection resolution, time to healing and duration of postoperative antibiotics were measured. In 137 cases, 88.3% of infections resolved. Infection was eradicated in 22 patients without postoperative systemic antibiotics. About 82.5% of wounds healed, with an average healing time of 11.3 weeks. Healing time was significantly increased for the co-morbidities of diabetes and PAD (p =< .05) and for those requiring prolonged systemic postoperative antibiotics. Conservative surgical debridement and implantation of local antibiotic impregnated calcium sulfate is safe and effective in managing complex foot infections. We advocate early surgical intervention before deeper tissue involvement to help preserve lower limb structure and function.

Susceptibility of monomicrobial or polymicrobial biofilms derived from infected diabetic foot ulcers to topical or systemic antibiotics in vitro.

Diabetic foot ulcers can become chronic and non-healing despite systemic antibiotic treatment. The penetration of systematically-administered antibiotics to the site of infection is uncertain, as is the effectiveness of such levels against polymicrobial biofilms. We have developed an in vitro model to study the effectiveness of different treatments for infected diabetic foot ulcers in a wound-like environment and compared the activity of systemic levels of antibiotics with that for topically applied antibiotics released from calcium sulfate beads. This is the first study that has harvested bacteria from diabetic foot infections and recreated similar polymicrobial biofilms to those present in vivo for individual subjects. After treatment with levels of gentamicin attained in serum after systemic administration (higher than corresponding tissues concentrations) we measured a 0-2 log reduction in bacterial viability of P. aeruginosa, S. aureus or a polymicrobial biofilm. Conversely, addition of gentamicin loaded calcium sulfate beads resulted in 5-9 log reductions in P. aeruginosa, S aureus and polymicrobial biofilms derived from three subjects. We conclude that systemically administered antibiotics are likely to be inadequate for successfully treating these infections, especially given the vastly increased concentrations required to inhibit cells in a biofilm, and that topical antibiotics provide a more effective alternative.

Biotic interchange between the Indian subcontinent and mainland Asia through time.

Biotic interchange after the connection of previously independently evolving floras and faunas is thought to be one of the key factors that shaped global biodiversity as we see it today. However, it was not known how biotic interchange develops over longer time periods of several million years following the secondary contact of different biotas. Here we present a novel method to investigate the temporal dynamics of biotic interchange based on a phylogeographical meta-analysis by calculating the maximal number of observed dispersal events per million years given the temporal uncertainty of the underlying time-calibrated phylogenies. We show that biotic influx from mainland Asia onto the Indian subcontinent after Eocene continental collision was not a uniform process, but was subject to periods of acceleration, stagnancy and decrease. We discuss potential palaeoenvironmental causes for this fluctuation.

Calcium sulphate as a drug delivery system in a deep diabetic foot infection.

Treating diabetic foot infection is costly, time consuming and challenging for the patient and clinician alike. It requires a multidisciplinary approach to provide a favourable outcome but all too often results in amputation. We present a patient with Type 2 diabetes who attended clinic with a limb threatening foot infection complicated by osteomyelitis and requiring emergency surgery and antibiotic administration. Our patient underwent surgery by means of an incision and drainage procedure with local antibiotic administration to augment systemic antibiotics. The wound was packed with calcium sulphate (Stimulan(®) Biocomposites Ltd.) impregnated with gentamicin and vancomycin to enable high antibiotic concentrations at the site of infection. The patient made a full recovery at four months requiring only minimal bone excision to maintain a functional foot. This case demonstrates an alternative route for antibiotic administration to overcome some of the limitations of systemic administration including penetration at the site of infection, systemic toxicity, prolonged hospital admission and cost. This route of administration is being increasingly used as an alternative to systemic antibiotics at our centre.

Evaluation of an Inexpensive Growth Medium for Direct Detection of Escherichia coli in Temperate and Sub-Tropical Waters.

The cost and complexity of traditional methods for the detection of faecal indicator bacteria, including E. coli, hinder widespread monitoring of drinking water quality, especially in low-income countries and outside controlled laboratory settings. In these settings the problem is exacerbated by the lack of inexpensive media for the detection of E. coli in drinking water. We developed a new low-cost growth medium, aquatest (AT), and validated its use for the direct detection of E. coli in temperate and sub-tropical drinking waters using IDEXX Quanti-Tray®. AT was compared with IDEXX Colilert-18® and either EC-MUG or MLSB for detecting low levels of E. coli from water samples from temperate (n = 140; Bristol, UK) and subtropical regions (n = 50, Pretoria/Tshwane, South Africa). Confirmatory testing (n = 418 and 588, respectively) and the comparison of quantitative results were used to assess performance. Sensitivity of AT was higher than Colilert-18® for water samples in the UK [98.0% vs. 86.9%; p<0.0001] and South Africa [99.5% vs. 93.2%; p = 0.0030]. There was no significant difference in specificity, which was high for both media (>95% in both settings). Quantitative results were comparable and within expected limits. AT is reliable and accurate for the detection of E. coli in temperate and subtropical drinking water. The composition of the new medium is reported herein and can be used freely.

High-bolus dose tirofiban compared with abciximab in primary percutaneous coronary intervention: a propensity score-matched outcome study.

AIMS: The objective of this study was to analyse the outcomes of patients treated with high-bolus dose (HBD) tirofiban compared with abciximab at the time of primary PCI (PPCI) for ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: Data from two large UK tertiary centres, with differing protocols for glycoprotein IIb/IIIa inhibitor use during PPCI, were pooled. Propensity scores were calculated based on important covariates, and HBD tirofiban-treated patients were matched to abciximab-treated controls on a one-to-one basis. This resulted in 942 well matched pairs. Survival analysis demonstrated no significant difference in mortality between HBD tirofiban and abciximab either at 30 days (HBD tirofiban 3.7% vs. abciximab 3.2%; HR 1.01 [95% CI: 0.92-1.10], p=0.96) or at three years (HBD tirofiban 9.4% vs. abciximab 9.3%; HR 1.15 [95% CI: 0.79-1.67], p=0.45). Rates of stent thrombosis at 30 days were also similar (HBD tirofiban 12 [1.3%] vs. abciximab 8 [0.8%], p=0.50) but thrombocytopaenia was more common with abciximab (HBD tirofiban 3 [0.3%] vs. abciximab 17 [1.8%], p=0.001). CONCLUSIONS: In this observational study of adjunctive GP IIb/IIIa inhibitor treatment in PPCI, we found no difference in survival between HBD tirofiban-treated patients compared with propensity score-matched abciximab-treated controls up to three-year follow-up.

Borneo and Indochina are major evolutionary hotspots for Southeast Asian biodiversity.

Tropical Southeast (SE) Asia harbors extraordinary species richness and in its entirety comprises four of the Earth's 34 biodiversity hotspots. Here, we examine the assembly of the SE Asian biota through time and space. We conduct meta-analyses of geological, climatic, and biological (including 61 phylogenetic) data sets to test which areas have been the sources of long-term biological diversity in SE Asia, particularly in the pre-Miocene, Miocene, and Plio-Pleistocene, and whether the respective biota have been dominated by in situ diversification, immigration and/or emigration, or equilibrium dynamics. We identify Borneo and Indochina, in particular, as major "evolutionary hotspots" for a diverse range of fauna and flora. Although most of the region's biodiversity is a result of both the accumulation of immigrants and in situ diversification, within-area diversification and subsequent emigration have been the predominant signals characterizing Indochina and Borneo's biota since at least the early Miocene. In contrast, colonization events are comparatively rare from younger volcanically active emergent islands such as Java, which show increased levels of immigration events. Few dispersal events were observed across the major biogeographic barrier of Wallace's Line. Accelerated efforts to conserve Borneo's flora and fauna in particular, currently housing the highest levels of SE Asian plant and mammal species richness, are critically required.

Soils on exposed Sunda shelf shaped biogeographic patterns in the equatorial forests of Southeast Asia.

The marked biogeographic difference between western (Malay Peninsula and Sumatra) and eastern (Borneo) Sundaland is surprising given the long time that these areas have formed a single landmass. A dispersal barrier in the form of a dry savanna corridor during glacial maxima has been proposed to explain this disparity. However, the short duration of these dry savanna conditions make it an unlikely sole cause for the biogeographic pattern. An additional explanation might be related to the coarse sandy soils of central Sundaland. To test these two nonexclusive hypotheses, we performed a floristic cluster analysis based on 111 tree inventories from Peninsular Malaysia, Sumatra, and Borneo. We then identified the indicator genera for clusters that crossed the central Sundaland biogeographic boundary and those that did not cross and tested whether drought and coarse-soil tolerance of the indicator genera differed between them. We found 11 terminal floristic clusters, 10 occurring in Borneo, 5 in Sumatra, and 3 in Peninsular Malaysia. Indicator taxa of clusters that occurred across Sundaland had significantly higher coarse-soil tolerance than did those from clusters that occurred east or west of central Sundaland. For drought tolerance, no such pattern was detected. These results strongly suggest that exposed sandy sea-bed soils acted as a dispersal barrier in central Sundaland. However, we could not confirm the presence of a savanna corridor. This finding makes it clear that proposed biogeographic explanations for plant and animal distributions within Sundaland, including possible migration routes for early humans, need to be reevaluated.

Impact of implementation of evidence-based strategies to reduce door-to-balloon time in patients presenting with STEMI: continuous data analysis and feedback using a statistical process control plot.

BACKGROUND: Strategies to reduce DTB (door-to-balloon) time have been previously described. However, there is no well-established data-monitoring system that can be used for prompt feedback. The aims of this study were to use statistical process control (SPC) methodology to measure current processes, to provide real-time feedback on the impact of a change in service delivery and to identify individual outliers for specific investigation. METHODS: A prospective study was conducted in a tertiary centre in North England. Data were collected for 841 consecutive STEMI patients from the local district undergoing PPCI. The impact on median DTB time after changes in protocols were prospectively determined. RESULTS: Median DTB times fell significantly as a result of changes in protocol. The upper control limit (UCL) decreased from 209 to 86 min and narrower control limits indicated improved performance. The main outliers included patients presenting to the Accident and Emergency department and patients who developed STEMI while being treated in non-cardiology wards for other reasons (18.3% of the study population). CONCLUSIONS: SPC provides a statistically robust mechanism for assessing the effect of process redesign interventions, and in this context provides a clear visual representation of DTB times for individual patients. Identification of significant outliers allows investigation of any variation with a special cause. It allows a unit to identify when a system of service delivery, albeit stable, is inadequate and needs redesign and can monitor the impact of changes in protocol.

The current refugial rainforests of Sundaland are unrepresentative of their biogeographic past and highly vulnerable to disturbance.

Understanding the historical dynamics of forest communities is a critical element for accurate prediction of their response to future change. Here, we examine evergreen rainforest distribution in the Sunda Shelf region at the last glacial maximum (LGM), using a spatially explicit model incorporating geographic, paleoclimatic, and geologic evidence. Results indicate that at the LGM, Sundaland rainforests covered a substantially larger area than currently present. Extrapolation of the model over the past million years demonstrates that the current "island archipelago" setting in Sundaland is extremely unusual given the majority of its history and the dramatic biogeographic transitions caused by global deglaciation were rapid and brief. Compared with dominant glacial conditions, lowland forests were probably reduced from approximately 1.3 to 0.8 x 10(6) km(2) while upland forests were probably reduced by half, from approximately 2.0 to 1.0 x 10(5) km(2). Coastal mangrove and swamp forests experienced the most dramatic change during deglaciations, going through a complete and major biogeographic relocation. The Sundaland forest dynamics of fragmentation and contraction and subsequent expansion, driven by glacial cycles, occur in the opposite phase as those in the northern hemisphere and equatorial Africa, indicating that Sundaland evergreen rainforest communities are currently in a refugial stage. Widespread human-mediated reduction and conversion of these forests in their refugial stage, when most species are passing through significant population bottlenecks, strongly emphasizes the urgency of conservation and management efforts. Further research into the natural process of fragmentation and contraction during deglaciation is necessary to understand the long-term effect of human activity on forest species.

Funnel plots for comparing performance of PCI performing hospitals and cardiologists: demonstration of utility using the New York hospital mortality data.

BACKGROUND: The New York State Department of Health collects and reports outcome data on the hospitals and cardiologists who perform percutaneous coronary intervention (PCI) to allow them to examine their quality of care. Results are provided in tabular form. However funnel plots are the display method of choice for comparison of institutions and operators, using the principles of statistical process control (SPC). We aimed to demonstrate that funnel plots, which aid a meaningful interpretation of the results, can be derived from the New York PCI dataset. METHODS: The risk-adjusted mortality rates for 48 hospitals and cardiologists performing PCI were used for this analysis. Funnel plots (with control limits at 3 and 2 sigma) of all hospitals and operators performing PCI procedures were generated. Separate plots for emergency and nonemergency PCI procedures were derived. RESULTS: 149,888 patients underwent PCI procedures between January 1, 2002 and December 31, 2004. The 3-year risk-adjusted mortality rates for all PCI patients ranged from 0.00 to 1.37%. The funnel plots show risk-adjusted mortality rates against the denominator for that percentage (number of cases), displayed as a scatter plot and compared with the binomial funnel plot calculated around the mean for all cases reported. The risk-adjusted mortality rates of all hospitals were within 3 sigma (99.8%) upper control limits. The risk-adjusted mortality rates for three hospitals were above or on the upper warning limit (2 sigma control limit, equating to the 95% confidence interval) and three hospitals had risk-adjusted mortality rates below the 2 and 3 sigma control limits. CONCLUSION: The SPC funnel plot is an easy-to-interpret, risk-adjusted means of identifying units whose performance, in terms of mortality, diverges significantly from the population mean. Funnel plots may be applied to a complex dataset and allow a visual comparison of data derived from multiple healthcare units. Variation is readily identified permitting hospitals and cardiologists to appraise their practices so that effective quality improvement may take place.

Interactions of some common pathogenic bacteria with Acanthamoeba polyphaga.

Protozoan grazing is a major trophic pathway whereby the biomass re-enters the food web. Nonetheless, not all bacteria are digested by protozoa and the number known to evade digestion, resulting in their environmental augmentation, is increasing. We investigated the interactions of Bacillus cereus, Enterococcus faecalis, Enteropathogenic Escherichia coli (EPEC), Listeria monocytogenes, Salmonella enterica serovar Typhimurium, and methicillin-sensitive Staphylococcus aureus (MSSA), with the amoeba, Acanthamoeba polyphaga. There was evidence of predation of all bacterial species except L. monocytogenes and S. aureus, where extracellular numbers were significantly higher when cultured with amoebae compared with growth in the absence of amoebae. Intracellular growth kinetic experiments and fluorescent confocal microscopy suggest that S. aureus survived and may even multiply within A. polyphaga, whereas there was no apparent intra-amoebal replication of L. monocytogenes and higher numbers were likely sustained on metabolic waste products released during coculture.

Cumulative funnel plots for the early detection of interoperator variation: retrospective database analysis of observed versus predicted results of percutaneous coronary intervention.

OBJECTIVE: To use funnel plots and cumulative funnel plots to compare in-hospital outcome data for operators undertaking percutaneous coronary interventions with predicted results derived from a validated risk score to allow for early detection of variation in performance. DESIGN: Analysis of prospectively collected data. SETTING: Tertiary centre NHS hospital in the north east of England. PARTICIPANTS: Five cardiologists carrying out percutaneous coronary interventions between January 2003 and December 2006. MAIN OUTCOME MEASURES: In-hospital major adverse cardiovascular and cerebrovascular events (in-hospital death, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accident) analysed against the logistic north west quality improvement programme predicted risk, for each operator. Results are displayed as funnel plots summarising overall performance for each operator and cumulative funnel plots for an individual operator's performance on a case series basis. RESULTS: The funnel plots for 5198 patients undergoing percutaneous coronary interventions showed an average observed rate for major adverse cardiovascular and cerebrovascular events of 1.96% overall. This was below the predicted risk of 2.06% by the logistic north west quality improvement programme risk score. Rates of in-hospital major adverse cardiovascular and cerebrovascular events for all operators were within the 3sigma upper control limit of 2.75% and 2sigma upper warning limit of 2.49%. CONCLUSION: The overall in-hospital major adverse cardiovascular and cerebrovascular events rates were under the predicted event rate. In-hospital rates after percutaneous coronary intervention procedure can be monitored successfully using funnel and cumulative funnel plots with 3sigma control limits to display and publish each operator's outcomes. The upper warning limit (2sigma control limit) could be used for internal monitoring. The main advantage of these charts is their transparency, as they show observed and predicted events separately. By this approach individual operators can monitor their own performance, using the predicted risk for their patients but in a way that is compatible with benchmarking to colleagues, encapsulated by the funnel plot. This methodology is applicable regardless of variations in individual operator case volume and case mix.

Secondary prevention following coronary artery bypass grafting has improved but remains sub-optimal: the need for targeted follow-up.

A focused review of secondary preventive medication following revascularisation provides an opportunity to ensure optimal use of these agents. A retrospective analysis of our in-house cardiothoracic surgical database was performed to identify patients undergoing non-emergency, elective surgical revascularisation discharged on four secondary preventive medications: aspirin; beta-blockers; ACE-inhibitors and statins. Of 2749 patients studied, 2302 underwent isolated coronary artery bypass grafting (CABG), mean age 65.5 years (S.D. 9.15). Overall, 2536 (92%) patients were prescribed aspirin. Beta-blockers were prescribed in 2171 (79%) patients overall, in 1096/1360 (81%) of patients with a history of myocardial infarction and in 465/619 (75%) of patients with left ventricular systolic dysfunction (LVSD). Overall, 1518 (55%) patients were prescribed an ACE-inhibitor and 179 (6.5%) an angiotensin receptor blocker (ARB); one of these agents was prescribed in 446/619 (72%) patients with LVSD and 915/1360 (67%) patients with a history of previous myocardial infarction. Overall, 2518 (92%) patients were prescribed a statin. Secondary preventive therapies are prescribed more commonly on discharge after CABG than in previous studies, but there is a continuing under-utilisation of ACE-inhibitors. To maximise the potential benefits of these agents, further study is required to understand why they are not prescribed.

Fast wavelet estimation of weak biosignals.

Wavelet-based signal processing has become commonplace in the signal processing community over the past decade and wavelet-based software tools and integrated circuits are now commercially available. One of the most important applications of wavelets is in removal of noise from signals, called denoising, accomplished by thresholding wavelet coefficients in order to separate signal from noise. Substantial work in this area was summarized by Donoho and colleagues at Stanford University, who developed a variety of algorithms for conventional denoising. However, conventional denoising fails for signals with low signal-to-noise ratio (SNR). Electrical signals acquired from the human body, called biosignals, commonly have below 0 dB SNR. Synchronous linear averaging of a large number of acquired data frames is universally used to increase the SNR of weak biosignals. A novel wavelet-based estimator is presented for fast estimation of such signals. The new estimation algorithm provides a faster rate of convergence to the underlying signal than linear averaging. The algorithm is implemented for processing of auditory brainstem response (ABR) and of auditory middle latency response (AMLR) signals. Experimental results with both simulated data and human subjects demonstrate that the novel wavelet estimator achieves superior performance to that of linear averaging.

Foot pressures during level walking are strongly associated with pressures during other ambulatory activities in subjects with diabetic neuropathy.

OBJECTIVE: To assess the relationship between foot pressures measured during level walking and other types of ambulatory activity in subjects with diabetes mellitus (DM) and peripheral neuropathy (PN). DESIGN: Descriptive survey with repeated measures. SETTING: University medical center. PARTICIPANTS: Convenience sample of 16 ambulatory subjects with DM and PN. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Peak pressure and pressure-time integral (PTI) at the heel, great toe, first metatarsal head (MT1), and third metatarsal head (MT3) during level walking, ramp climbing, stair climbing, and turning at a self-selected speed. RESULTS: Peak pressure and PTI during level walking correlated highly with pressures during ramp climbing (r range,.85-.97) and turning (r range,.75-.96) at all regions examined and with pressures during stair climbing at MT1 and MT3 (r range,.84-.91). Correlations between pressures during level walking and stair climbing were moderate at the great toe (r range,.46-.57) and poor at the heel (r range, -.12 to -.06). With few exceptions, pressures during ramp climbing, stair climbing, and turning were less than (P<.008) or equal to pressures during level walking. We found no activity-related differences in peak pressure or PTI independent of the effects of preferred walking speed. CONCLUSIONS: Results support the clinical evaluation of peak pressure during level walking as an efficient method to screen for maximum levels of stress on the foot as patients with DM and PN perform their daily activities.

Missing fossils, molecular clocks, and the origin of the Melastomataceae.

In a recent analysis of the historical biogeography of Melastomataceae, Renner, Clausing, and Meyer (2001; American Journal of Botany 88(7): 1290-1300) rejected the hypothesis of a Gondwana origin. Using a fossil-calibrated chloroplast DNA (ndhF) phylogeny, they placed the early diversification of Melastomataceae in Laurasia at the Paleocene/Eocene boundary (ca. 55 Ma) and suggested that long-distance oceanic dispersals in the Oligocene and Miocene (34 to 5 Ma) account for its range expansion into South America, Africa, and Madagascar. Their critical assumption-that oldest northern mid-latitude melastome fossils reflect tribal ages and their geographic origins-may be erroneous, however, because of the sparse fossil record in the tropics. We show that rates of synonymous nucleotide substitutions derived by the Renner et al. (2001) model are up to three times faster than most published rates. Under a Gondwana-origin model advocated here, which includes dispersals from Africa to Southeast Asia via the "Indian ark" and emphasizes filter rather than either sweepstakes dispersal or strict vicariance, rates of nucleotide substitution fall within the range of published rates. We suggest that biogeographic reconstructions need to consider the paucity of Gondwanan fossils and that frequently overlooked interplate dispersal routes provide alternatives to vicariance, boreotropical dispersal, and long-distance oceanic dispersal as explanations for the amphi-oceanic disjunctions of many tropical rain forest plants.

Neocortical seizure termination by focal cooling: temperature dependence and automated seizure detection.

PURPOSE: The therapy for focal neocortical epilepsy remains suboptimal. We have, therefore, worked to develop techniques to cool small regions of the neocortical surface for seizure mapping and, ultimately, for long-term suppression of focal seizures. METHODS: We induced focal neocortical seizures in halothane-anesthetized rats by the microinjection of 4-aminopyridine (4-AP) into the motor cortex. The dura over the injection site was cooled with a Peltier device, and the temperature at the interface between dura and Peltier was measured with a thermocouple. In some experiments, seizures were automatically detected by a computer program that activated the Peltier device. RESULTS: Monopolar EEG indicated that our seizures were focal and suppressed when cooling was applied directly over the injection site. The threshold temperature required to observe any reduction in seizure duration was 24 degrees C. The temperature gradient across the cooled neocortex was sharp, with the temperature increasing to 31 degrees C at 4 mm below the Peltier, which was cooled to 20 degrees C. Automatic seizure detection reduced the total seizure duration from 43.4 +/- 33.6 s to 5.6 +/- 5.3 s. CONCLUSIONS: Cooling terminates neocortical seizures when applied very close to the epileptogenic focus. The threshold for seizure termination (24 degrees C) may be lower than the threshold for termination of normal cortical activity, suggesting that this technique will not dissociate the anticonvulsant effect of cooling from the disruption of normal behavior. However, when coupled with automatic seizure detection, focal cooling remains an attractive option for development as a treatment for focal epilepsy.