Timing and climate forcing of volcanic eruptions for the past 2,500 years.

Volcanic eruptions contribute to climate variability, but quantifying these contributions has been limited by inconsistencies in the timing of atmospheric volcanic aerosol loading determined from ice cores and subsequent cooling from climate proxies such as tree rings. Here we resolve these inconsistencies and show that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years. Our results are based on new records of atmospheric aerosol loading developed from high-resolution, multi-parameter measurements from an array of Greenland and Antarctic ice cores as well as distinctive age markers to constrain chronologies. Overall, cooling was proportional to the magnitude of volcanic forcing and persisted for up to ten years after some of the largest eruptive episodes. Our revised timescale more firmly implicates volcanic eruptions as catalysts in the major sixth-century pandemics, famines, and socioeconomic disruptions in Eurasia and Mesoamerica while allowing multi-millennium quantification of climate response to volcanic forcing.

Metrics of salbutamol use as predictors of future adverse outcomes in asthma.

BACKGROUND: Beta-agonist overuse is associated with adverse outcomes in asthma, however, the relationships between different metrics of salbutamol use and future risk are uncertain. OBJECTIVE: To investigate the relationship between metrics of salbutamol use and adverse outcome. METHODS: In a 24-week randomized controlled trial of 303 asthma patients at risk of severe exacerbations which compared the efficacy and safety of combination budesonide/formoterol inhaler according to a single inhaler regimen (SMART) with a fixed-dose regimen with salbutamol as reliever ('Standard'), actual medication use was measured by electronic monitoring (Australian New Zealand Clinical Trials Registry Number ACTRN12610000515099). A nested cohort study explored the relationship between metrics of baseline salbutamol use over 2 weeks and future severe asthma exacerbations, poor asthma control (ACQ-5 ≥ 1.5) or 'extreme' salbutamol overuse (> 32 salbutamol actuations/24-h period). RESULTS: Higher mean daily salbutamol use (per two actuations/day) [Odds ratio (OR) (95% CI) 1.24 (1.06-1.46)], higher days of salbutamol use (per 2 days in 2 weeks) [OR 1.15 (1.00-1.31)] and higher maximal 24-h use (per two actuations/day) [OR 1.09 (1.02-1.16)] were associated with future severe exacerbations. Higher mean daily salbutamol use was associated with future poor asthma control [OR 1.13 (1.02-1.26)]. Higher mean daily salbutamol use [OR 2.73 (1.84-4.07)], number of days of use [OR 1.46 (1.24-1.71)], and maximal daily use [OR 1.57 (1.31-1.89)] were associated with an increased risk of future extreme salbutamol overuse. CONCLUSION AND CLINICAL RELEVANCE: Electronically recorded frequency of current salbutamol use is a strong predictor of risk of future adverse outcomes in asthma, with average daily use performing the best. These findings provide new information for clinicians considering metrics of salbutamol as predictors of future adverse outcomes in asthma.

Changes in nurses' decision making during a 12-h day shift.

BACKGROUND: Although shift work is necessary in many health-care settings, research suggests that it can have detrimental effects on performance in health-care providers. AIMS: To determine if a change in decision-making occurred across a 12-h day shift in a sample of registered nurses. METHODS: The participants were nurses working a 12-h day shift (7 a.m.-7 p.m.) at a large hospital in the south-eastern USA. Participants completed a policy-capturing questionnaire, examining their likelihood of calling a physician in response to specific patient symptoms, at the beginning and end of the shift. They also completed self-report surveys on alertness, stress and sleepiness. RESULTS: Sixty-five nurses completed the study, an overall response rate of 41%. Participants significantly changed their decision-making policies from the beginning to the end of the work shift and also became significantly less alert and more stressed. However, there was no correlation between decision-making and reported alertness and stress. CONCLUSIONS: These results suggest that medical judgment in registered nurses changed from the beginning to the end of a 12-h day shift. One possible underlying mechanism responsible for the changes seen across the shift could be the ability to maintain attention, as suggested by the Controlled Attention Model. The current results expand upon previous research, indicating there are a variety of negative outcomes associated with shift work.

Diagnostic accuracy of small intestine ultrasonography using an oral contrast agent in Crohn's disease: comparative study from the UK.

AIM: To evaluate the usefulness of small intestine contrast-enhanced ultrasonography (SICUS) using an oral contrast agent in routine clinical practice by assessing the level of agreement with the established techniques, small bowel follow-through (SBFT) and computed tomography (CT), and diagnostic accuracy compared with the final diagnosis in the detection of small bowel Crohn's disease (CD) and luminal complications in a regional centre. MATERIALS AND METHODS: All symptomatic known or suspected cases of CD who underwent SICUS were retrospectively reviewed. The level of agreement between SICUS and SBFT, CT, histological findings, and C-reactive protein (CRP) level was assessed using kappa (κ) coefficient. Sensitivity was demonstrated using the final diagnosis as the reference standard defined by the outcome of clinical assessment, follow-up, and results of investigations other than SICUS. RESULTS: One hundred and forty-three patients underwent SICUS of these 79 (55%) were female. Eighty-six (60%) were known to have CD and 57 (40%) had symptoms suggestive of intestinal disease with no previous diagnosis. Forty-six (55%) of the known CD patients had had at least one previous surgical resection. The sensitivity of SICUS in detecting active small bowel CD in known CD and undiagnosed cases was 93%. The kappa coefficient was 0.88 and 0.91 with SBFT and CT, respectively. SICUS detected nine patients who had one or more small bowel strictures and six patients with a fistula all detected by SBFT or CT. CONCLUSION: SICUS is not only comparable to SBFT and CT but avoids radiation exposure and should be more widely adopted in the UK as a primary diagnostic procedure and to monitor disease complications in patients with CD.

Land clearance in the irish neolithic: new evidence and interpretation.

Time scales are derived, from radiocarbon dating of pollen diagrams, for Neolithic land clearance at three Irish sites. Three stages are distinguished beginning in the 4th millennium B.C.: stage A, clearance and farming (possibly arable), 100 to 400 years; stage B, farming (possibly pastoral), 150 to 200 years; and stage C, forest regeneration, 50 to 100 years.

The relation between composite ultrasound measures and the DAS28 score, its components and acute phase markers in adult RA.

OBJECTIVES: Ultrasound (US) provides measurements of synovial morphology and vascularity. However, on an individual joint basis in RA, US measures do not relate well to clinical signs. This study investigates the relationship between composite US measures and the 28-joint disease activity score (DAS28), its components and acute phase markers in adult RA. METHODS: RA synovial disease activity was recorded in 50 patients by: (i) the DAS28 score; (ii) ESR and CRP; and (iii) US using Grey scale (GS) and power Doppler (PD) measures of PIP and MCP joints to derive composite US scores based on abnormal counts and severity. A total of 25 control subjects were studied to define normal US appearances. The relation between each measure of synovial disease was determined by Spearman correlation analysis. RESULTS: There was a significant relation between the DAS28 and the GS joint count (GSJC, Spearman's r = 0.4; P = 0.004) and severity score (GSJS, r = 0.34; P = 0.016) and the PD joint count (PDJC, r = 0.32; P = 0.028). There was a significant relation between the ESR and PDJC (r = 0.37; P = 0.007) and PD joint severity score (PDJS, r = 0.38; P = 0.006) and between the CRP and PDJS (r = 0.29; P = 0.04). The remaining components of the DAS28 related poorly to all US measures, except the tender joint count, which related significantly to the GS but not the PD measures. CONCLUSIONS: Composite US markers of synovial disease relate significantly to the DAS28 score and ESR/CRP in adult RA, but not as well with individual clinical joint counts and the patient's global assessment.

A two centre observational study of simultaneous pulse oximetry and arterial oxygen saturation recordings in intensive care unit patients.

The influence of variables that might affect the accuracy of pulse oximetry (SpO2) recordings in critically ill patients is not well established. We sought to describe the relationship between paired SpO2/SaO2 (oxygen saturation via arterial blood gas analysis) in adult intensive care unit (ICU) patients and to describe the diagnostic performance of SpO2 in detecting low SaO2 and PaO2. A paired SpO2/SaO2 measurement was obtained from 404 adults in ICU. Measurements were used to calculate bias, precision, and limits of agreement. Associations between bias and variables including vasopressor and inotrope use, capillary refill time, hand temperature, pulse pressure, body temperature, oximeter model, and skin colour were estimated. There was no overall statistically significant bias in paired SpO2/SaO2 measurements; observed limits of agreement were +/-4.4%. However, body temperature, oximeter model, and skin colour, were statistically significantly associated with the degree of bias. SpO2 <89% had a sensitivity of 3/7 (42.9%; 95% confidence intervals, CI, 9.9% to 81.6%) and a specificity of 344/384 (89.6%; 95% CI 86.1% to 92.5%) for detecting SaO2 <89%. The absence of statistically significant bias in paired SpO2/SaO2 in adult ICU patients provides support for the use of pulse oximetry to titrate oxygen therapy. However, SpO2 recordings alone should be used cautiously when SaO2 recordings of 4.4% higher or lower than the observed SpO2 would be of concern. A range of variables relevant to the critically ill had little or no effect on bias.

Optimization of binding capacity and specificity of protein G on various solid matrices for immunoglobulins.

Streptococcal protein G is a more versatile and efficient alternative to staphylococcal protein A in purifying immunoglobin G (IgG) isotypes from various animal species. Optimizations are most dramatic with goat IgG, which binds protein G 55 times better than protein A. Using GammaBind G (a recombinant form of protein G (Genex Corp.)), we optimized binding capacity and specificity for IgG. Protein G was covalently coupled to three different matrices (CNBr-Sepharose, Tresyl-Sepharose, and Affigel-10) and compared with protein A-CNBr-Sepharose. Equal volumes of human, mouse, and goat serum samples were equilibrated into Hepes/NaOH buffers with various ionic strengths (i.e., concentrations of NaCl) and pH values and allowed to bind to affinity columns of proteins G and A. Bound ligands were eluted with 8.0 M urea, 0.05-M Tris/HCl, pH 8.00. Bound fractions were assayed for protein concentration and analyzed by sodium dodecyl sulfate polyacrylamide electrophoresis. The optimal conditions for binding IgG to protein G are 1.0 M NaCl and pH 8.0 for human, mouse, and goat.

Long-term treatment with oral enoximone for chronic congestive heart failure: the European experience.

The long-term safety and efficacy of the inotropic/vasodilatory agent enoximone (50 to 100 mg 3 times daily) were evaluated in 30 patients with chronic congestive heart failure (New York Heart Association classes II to IV). Nineteen patients had idiopathic dilated cardiomyopathy and 11 had ischemic heart disease. Patients were receiving maintenance therapy of digitalis and diuretics. Cardiac function was assessed at 12 week intervals (physical examination, exercise testing, chest x ray, echocardiography, radionuclide angiography, 24-hour Holter monitoring and blood chemistry). During a mean follow-up of 40 weeks, 6 patients died, due to noncardiac (n = 1) and sudden death (n = 1) and to cardiac failure (n = 4) within 36 weeks of drug treatment. In the remaining patients New York Heart Association class improved in 18, was stationary in 5 and deteriorated in 1. Exercise capacity increased during the first 26 weeks and was maintained improved thereafter. Clinical improvement appeared not to wane with time. No change in heart rate, blood pressure and cardiothoracic ratio was observed. Echocardiographic left ventricular dimensions did not change significantly; however, the fractional shortening increased from baseline (14%) to 19% after 12 weeks, 17% after 26 weeks and 21% after 52 weeks (p less than 0.05). The preejection period/left ventricular ejection time ratio decreased from 0.74 to 0.35, 0.44 and 0.43 (p less than 0.05), respectively. There was an increase in radionuclide ejection fraction from 23% to 27% (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of sleep deprivation on performance: a meta-analysis.

To quantitatively describe the effects of sleep loss, we used meta-analysis, a technique relatively new to the sleep research field, to mathematically summarize data from 19 original research studies. Results of our analysis of 143 study coefficients and a total sample size of 1.932 suggest that overall sleep deprivation strongly impairs human functioning. Moreover, we found that mood is more affected by sleep deprivation than either cognitive or motor performance and that partial sleep deprivation has a more profound effect on functioning than either long-term or short-term sleep deprivation. In general, these results indicate that the effects of sleep deprivation may be underestimated in some narrative reviews, particularly those concerning the effects of partial sleep deprivation.

Tephra-dated lowland landscape history of the north of Ireland, A.D. 750-1150.

Tephra-linked pollen diagrams from lowland raised peats at three sites in the north of Ireland show extensive landscape changes between A.D. 750 and A.D. 1150. By A.D. 860 woodland had been cleared and agricultural activity was widespread but, by the start of the twelfth century, woods had regenerated and agriculture had declined. The gap in the Irish dendrochronological record between A.D. 730 and A.D. 850 is bridged by timbers from corn grinding mills, strengthening the case for spreading arable agriculture at this time.

Differential effects of permanent and rotating shifts on self-report sleep length: a meta-analytic review.

STUDY OBJECTIVES: The current study used the meta-analytic technique to quantitatively assess the effects of permanent and rotating shift-work schedules on sleep length. DESIGN: A meta-analysis was completed on 36 primary studies resulting in 165 effect sizes. Effect sizes comparing shift-workers to a permanent day shift control group were calculated for permanent evening shifts, permanent night shifts, and morning, evening, and night shifts worked as part of slowly and rapidly rotating shift systems. SETTING: NA PATIENTS OR PARTICIPANTS: NA INTERVENTIONS: NA RESULTS: Permanent night shifts resulted in a decrease, whereas permanent evening shifts resulted in an increase in sleep length. The shifts within rotating schedules followed the same pattern, with the addition of morning shifts having a moderate detrimental effect on sleep length. Furthermore, the speed of shift rotation had an impact. Slowly rotating shifts, in general, had the least detrimental effect on sleep length of the permanent and rotating shift-work schedules studied here. The pattern of effects among morning, evening, and night shifts was the same for rapidly and slowly rotating shifts, with night shifts having the greatest detrimental effect, morning shifts having a moderate detrimental effect and evening shifts having a positive effect on sleep length. In addition, nights on rotating shifts had a greater negative effect on sleep length than permanent night shifts. CONCLUSIONS: Slowly rotating shifts have the least negative impact on sleep length of shift-work schedules including a night shift. However, permanent night shifts could be an alternative shift-work schedule in operational settings that require many workers at night.

Sleep deprivation in the rat: XIII. The effect of hypothyroidism on sleep deprivation symptoms.

Previous studies of rats subjected to total sleep deprivation by the disk-over-water method had shown a large increase in energy expenditure (EE) and an initial increase followed by a later decrease in body temperature (Tb). It had been proposed that the increase in Tb resulted from regulation toward a higher temperature or setpoint, that the later decline in Tb resulted from excessive heat loss, and that the increase in EE supported both of these thermoregulatory changes. To evaluate this proposed role of the increase in EE, we examined whether blunting the EE rise in sleep-deprived rats by making them hypothyroid attenuated and/or shortened the initial increase in Tb and accelerated the later decline in Tb. Rats made hypothyroid by propylthiouracil administration (TxD rats) were totally sleep deprived and compared to hypothyroid yoked control (TxC) rats and to previously studied, untreated, totally sleep-deprived (TSD) rats. Neither TxD nor TxC rats showed large increases in EE like those of TSD rats. TxD rats did not initially increase Tb, as TSD rats had. Presumably, TSD rats had been able to support an initially elevated Tb, in spite of excessive heat loss, by large increases in EE, although even these increases were eventually insufficient. TxD rats showed much earlier and greater declines in Tb than TxC and TSD rats, eventually becoming severely hypothermic. These results support the interpretation that the large increase in EE previously seen in TSD rats had been compensatory for deprivation-induced thermoregulatory deficits. TxD rats survived an average of 17.1 days, which was not significantly different from survival time in TSD rats. However, there were differences in mortal processes between the two groups. TxD rats died or were sacrificed after chronic, severe hypothermia without observable signs of other morbid pathology. TSD rats had not shown similarly low Tb until just prior to death, but had shown signs of severe pathology, including severely debilitated appearance, disheveled fur, and severe lesions on their tails and on the plantar surfaces of their paws. These signs were diminished or absent in TxD rats, possibly due to blunted EE, lower Tb, or other effects of hypothyroidism. Because the skin changes seen in TSD rats were minimal in TxD rats, they could not have been responsible for the excessive heat loss.

Sleep deprivation in the rat: XI. The effect of guanethidine-induced sympathetic blockade on the sleep deprivation syndrome.

In earlier studies, rats totally deprived of sleep by a disk-over-water apparatus (TSD rats) had shown an increase in energy expenditure (EE) that could not be explained by increased motor activity or the metabolic expense of wakefulness. Excessive activation of a calorigenic mediator was a possibility, and norepinephrine-mediated sympathetic activation was the most likely candidate, because plasma norepinephrine (NE) levels had risen sharply in TSD rats. To determine whether this activation was necessary for increased EE in sleep deprived rats, the peripheral sympathetic blocking agent guanethidine (GU) was administered to six sleep-deprived (GD) rats and their yoked control (GC) rats. GU attenuated the increase in NE previously seen in TSD rats, but the increase in EE was not attenuated. Apparently, NE-mediated sympathetic activation was not critical for increased EE in sleep-deprived rats. On the other hand, plasma epinephrine (EPI) levels were significantly increased in GD (but not in GC) rats above those previously seen in TSD rats, suggesting the substitution of one calorigenic mediator for another in response to an abnormally elevated need for EE. Temperature data suggest that increased need for EE could arise from an elevated temperature setpoint and an inability to retain body heat. GD (but not GC) rats also showed other effects previously seen in TSD rats, including debilitated appearance; severe ulcerative and hyperkeratotic lesions on the tails and plantar surfaces; initially increased and later decreased body temperature; decreased plasma thyroxine; increased triiodothyronine-thyroxine ratio; and eventual death. Evidently, NE-mediated sympathetic activation was not critical to any of these effects, although a role for catecholamines cannot be ruled out.

Sleep deprivation in the rat: IX. Recovery.

Eight rats were subjected to total sleep deprivation, paradoxical sleep deprivation, or high amplitude sleep deprivation until they showed major deprivation-induced changes. Then they were allowed to sleep ad lib. Three rats that had shown the largest temperature declines died within two to six recovery days. During the first 15 days of ad lib sleep, surviving rats showed complete or almost complete reversal of the following deprivation-induced changes: debilitated appearance, lesions on the paws and tail, high energy expenditure, large decreases in peritoneal temperature, high plasma epinephrine and norepinephrine levels, and low thyroxine levels. The most prominent features of recovery sleep in all rats were immediate and large rebounds of paradoxical sleep to far above baseline levels, followed by lesser temporally extended rebounds. Rebounds of high amplitude non-rapid eye movement (NREM) sleep occurred only in some rats and were smaller and less immediate.

Stability of long-term renal function in heart transplant patients treated with induction therapy and low-dose cyclosporine.

Long-term renal function was evaluated in heart transplant recipients who were treated with antilymphocyte globulin induction therapy and low-dose cyclosporine therapy. Although an initial 16% drop in the glomerular filtration rate occurred, long-term follow-up revealed stability of renal function. Four-year patient survival was 77.6%. Use of induction therapy with low-dose cyclosporine may preserve renal function without compromising long-term patient survival.

Treatment of porcine cysticercosis with albendazole.

In a randomized, controlled study, the efficacy and safety of two different schemes of albendazole therapy for treatment of porcine cysticercosis were tested. Seventeen naturally infected pigs were divided into three groups and treated per os with albendazole (50 mg/kg single dose), albendazole (30 mg/kg every day for three days), or given no treatment, respectively. Serologic responses were monitored with the enzyme-linked electroimmunotransfer blot assay. Pigs were humanely killed 12 weeks after treatment, necropsied, and the number of parasites was recorded. Scolex evagination was used to assess viability of the cysts. Both albendazole-treated groups had significant side effects (anorexia, lethargy). Only a single viable cyst was recovered from the brain of one animal after therapy in the multiple-dose group, and the single-dose therapy left 11% of the cysts viable. In contrast, more than 90% of muscle cysts were found to be viable in the untreated group. Although albendazole therapy for three days was found to be highly effective, side effects and the need for multiple doses would still prevent its widespread use.

Use of sentinel pigs to monitor environmental Taenia solium contamination. The Cysticercosis Working Group in Peru (CWG).

We tested a novel approach to assay Taenia solium prevalence using the enzyme-linked immunoelectrotransfer blot assay in sentinel piglets to determine environmental contamination with T. solium eggs in a disease-endemic zone in Peru. Twelve sentinel piglets from an area where the disease is not present were tested at two months of age, moved to an area where the disease is endemic, and retested at the of age nine months. Sentinel piglets native from this T. solium-endemic area were also tested concurrently at two and nine months of age. Of the non-native pigs, 33% (4 of 12) acquired new infection. Of the 28 native pigs tested, 64% (18 of 28) acquired the infection. In a subset of the native piglets from seronegative sows, 44% (4 of 9) were infected at five months of age. Serodiagnosis of sentinel piglets is a practical method to detect T. solium eggs in the environment. Furthermore, it permits indirect assessment of human risk, which may be useful for monitoring the efficacy of intervention programs.

Discrepancies between cerebral computed tomography and western blot in the diagnosis of neurocysticercosis. The Cysticercosis Working Group in Peru (Clinical Studies Coordination Board).

Serum samples from sequential patients who underwent cerebral computed axial tomography (CT) scan in a Peruvian radiologic clinic were tested by the highly sensitive and specific enzyme-linked immunoelectrotransfer blot (EITB) test to detect antibodies to Taenia solium. The results of the EITB test were compared with those obtained by CT scan for the diagnosis of neurocysticercosis. Of the 383 patients sampled, 32 (8%) were seropositive. The results of CT and EITB were frequently discrepant. When compared with the EITB assay, the CT scan was 44% sensitive and 95% specific. The sensitivity of CT increased to 63% if less specific images (single calcifications, granulomas, or hydrocephalus) were included. The CT scan for diagnosis of cysticercosis can best be used in conjunction with a reliable serologic test such as the EITB.

Prevalence and comparison of serologic assays, necropsy, and tongue examination for the diagnosis of porcine cysticercosis in Peru.

Swine cysticercosis, a severe zoonotic disease which is part of the Taenia solium life cycle, causes major economic losses in pig husbandry. Throughout South America, farmers diagnose cysticercosis by examining the tongues of their pigs for cysticercus nodules. Farmers do not bring pigs believed to be infected to the slaughterhouse for fear of confiscation. Therefore, reliable statistics on porcine cysticercosis can only be acquired at the household level. We examined the utility of the tongue test as a diagnostic tool for porcine cysticercosis. The results of the tongue test was compared with 2 serologic methods for the detection of cysticercosis, the enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunoelectrotransfer blot assay (EITB), and with necropsy results. We examined 11 animals from an endemic area (Huancayo) and 42 animals from an area free of cysticercosis (Lima). The tongue test has a sensitivity of 70% and a specificity of 100%, the EITB a sensitivity and specificity of 100%, and the ELISA a sensitivity of 79% and a specificity of 75%. Thus, the tongue examination, being a test essentially without cost and having fair sensitivity and high specificity, can be useful in epidemiological surveys. Prevalence for porcine cysticercosis in Huancayo is 23.4% by tongue examination, 31.2% by necropsy, 37.7% by ELISA, and 51.9% by EITB.