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The aim of this study was to establish a comprehensive and yet parsimonious model of daily mobility activity in patients with neurological gait disorders. Patients (N = 240) with early-stage neurological (peripheral vestibular, cerebellar, hypokinetic, vascular or functional) gait disorders and healthy controls (N = 35) were clinically assessed with standardized scores related to functional mobility, balance confidence, quality of life, cognitive function, and fall history. Subsequently, daily mobility was recorded for 14 days by means of a body-worn inertial sensor (ActivPAL®). Fourteen mobility measures derived from ActivPAL recordings were submitted to principle component analysis (PCA). Group differences within each factor obtained from PCA were analyzed and hierarchical regression analysis was performed to identify predictive characteristics from clinical assessment for each factor. PCA yielded five significant orthogonal factors (i.e., mobility domains) accounting for 92.3% of the total variance from inertial-sensor-recordings: ambulatory volume (38.7%), ambulatory pattern (22.3%), postural transitions (13.3%), sedentary volume (10.8%), and sedentary pattern (7.2%). Patients' mobility performance only exhibited reduced scores in the ambulatory volume domain but near-to-normal scores in all remaining domains. Demographic characteristics, clinical scores, and fall history were differentially associated with each domain explaining 19.2-10.2% of their total variance. This study supports a low-dimensional five-domain model for daily mobility behavior in patients with neurological gait disorders that may facilitate monitoring the course of disease or therapeutic intervention effects in ecologically valid and clinically relevant contexts. Further studies are required to explore the determinants that may explain performance differences of patients within each of these domains and to examine the consequences of altered mobility behavior with respect to patients' risk of falling and quality of life.

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OBJECTIVES: The role of asymptomatic carriers in Clostridioides difficile infection (CDI) epidemiology is not fully understood. Our aim was to evaluate CD carriage prevalence on admission, associated risk factors, and the risk of developing CDI. METHODS: A 10-week surveillance program for CD carriage of all medical patients admitted to the Sheba Medical Centre was implemented, utilizing an admission rectal swab PCR. Healthcare facility-onset CDI (HO-CDI) was recorded and divided into HO-CDI diagnosed in CD carriers and non-carriers. RESULTS: A total of 4601 admissions were recorded in 3803 patients; 2368 patients had technically analysable rectal swabs, of whom 81 (3.4%) were CD carriers. A multivariate logistic regression model showed that previous hospitalization, old age (>85 years) and low Norton scores were significant independent predictors of CD carriage. Carriers were more likely to receive antimicrobial therapy during hospitalization than non-carriers were. The incidence of HO-CDI in non-carriers was 4.6 cases per 10 000 patient-days; the incidence of HO-CDI in carriers was 76.7 cases per 10 000 patient-days (RR 16.6, 95% CI 4.0-69.1, p .002). CONCLUSIONS: In a prospective study, the rate of CD carriage on admission in medical patients was 3.4%. CD carriers were older, frailer, and more likely to have been hospitalized recently. HO-CDI incidence was significantly higher among CD carriers than among non-carriers, with at least a third of CDI in screened patients developing in carriers. Targeted screening of high-risk groups for CD carriage should be further considered.

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Intensified surveillance during the 2009 A/H1N1 influenza pandemic in Israel resulted in large virological and serological datasets, presenting a unique opportunity for investigating the pandemic dynamics. We employ a conditional likelihood approach for fitting a disease transmission model to virological and serological data, conditional on clinical data. The model is used to reconstruct the temporal pattern of the pandemic in Israel in five age-groups and evaluate the factors that shaped it. We estimate the reproductive number at the beginning of the pandemic to beR= 1.4. We find that the combined effect of varying absolute humidity conditions and school vacations (SVs) is responsible for the infection pattern, characterized by three epidemic waves. Overall attack rate is estimated at 32% (28-35%) with a large variation among the age-groups: the highest attack rates within school children and the lowest within the elderly. This pattern of infection is explained by a combination of the age-group contact structure and increasing immunity with age. We assess that SVs increased the overall attack rates by prolonging the pandemic into the winter. Vaccinating school children would have been the optimal strategy for minimizing infection rates in all age-groups.

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We discuss to what extent disease transmission models provide reliable predictions. The concept of prediction is delineated as it is understood by modellers, and illustrated by some classic and recent examples. A precondition for a model to provide valid predictions is that the assumptions underlying it correspond to the reality, but such correspondence is always limited­all models are simplifications of reality. A central tenet of the modelling enterprise is what we may call the 'robustness thesis': a model whose assumptions approximately correspond to reality will make predictions that are approximately valid. To examine which of the predictions made by a model are trustworthy, it is essential to examine the outcomes of different models. Thus, if a highly simplified model makes a prediction, and if the same or a very similar prediction is made by a more elaborate model that includes some mechanisms or details that the first model did not, then we gain some confidence that the prediction is robust. An important benefit derived from mathematical modelling activity is that it demands transparency and accuracy regarding our assumptions, thus enabling us to test our understanding of the disease epidemiology by comparing model results and observed patterns. Models can also assist in decision-making by making projections regarding important issues such as intervention-induced changes in the spread of disease.

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Seasonal influenza appears as annual oscillations in temperate regions of the world, yet little is known as to what drives these annual outbreaks and what factors are responsible for their inter-annual variability. Recent studies suggest that weather variables, such as absolute humidity, are the key drivers of annual influenza outbreaks. The rapid, punctuated, antigenic evolution of the influenza virus is another major factor. We present a new framework for modelling seasonal influenza based on a discrete-time, age-of-infection, epidemic model, which allows the calculation of the model's likelihood function in closed form. This framework may be used to perform model inference and parameter estimation rigorously. The modelling approach allows us to fit 11 years of Israeli influenza data, with the best models fitting the data with unusually high correlations in which r > 0.9. We show that using actual weather to modulate influenza transmission rate gives better results than using the inter-annual means of the weather variables, providing strong support for the role of weather in shaping the dynamics of influenza. This conclusion remains valid even when incorporating a more realistic depiction of the decay of immunity at the population level, which allows for discrete changes in immunity from year to year.

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This paper presents new computational and modelling tools for studying the dynamics of an epidemic in its initial stages that use both available incidence time series and data describing the population's infection network structure. The work is motivated by data collected at the beginning of the H1N1 pandemic outbreak in Israel in the summer of 2009. We formulated a new discrete-time stochastic epidemic SIR (susceptible-infected-recovered) model that explicitly takes into account the disease's specific generation-time distribution and the intrinsic demographic stochasticity inherent to the infection process. Moreover, in contrast with many other modelling approaches, the model allows direct analytical derivation of estimates for the effective reproductive number (R(e)) and of their credible intervals, by maximum likelihood and Bayesian methods. The basic model can be extended to include age-class structure, and a maximum likelihood methodology allows us to estimate the model's next-generation matrix by combining two types of data: (i) the incidence series of each age group, and (ii) infection network data that provide partial information of 'who-infected-who'. Unlike other approaches for estimating the next-generation matrix, the method developed here does not require making a priori assumptions about the structure of the next-generation matrix. We show, using a simulation study, that even a relatively small amount of information about the infection network greatly improves the accuracy of estimation of the next-generation matrix. The method is applied in practice to estimate the next-generation matrix from the Israeli H1N1 pandemic data. The tools developed here should be of practical importance for future investigations of epidemics during their initial stages. However, they require the availability of data which represent a random sample of the real epidemic process. We discuss the conditions under which reporting rates may or may not influence our estimated quantities and the effects of bias.

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Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.

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BACKGROUND AND OBJECTIVE: This prospective, randomized, double-blinded study was designed to compare the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate. METHODS: Seventy-two patients were enrolled in six groups of 12 individuals each. In three groups, fentanyl was given as a bolus dose of 1.5 microg kg(-1), whereas the others received a remifentanil infusion at 0.5 microg kg(-1) min(-1). Five minutes later, propofol, thiopental or etomidate were titrated to a state of unresponsiveness. Assessment included the amounts of drug necessary for induction, haemodynamics and the times to apnoea, loss of eyelash reflex, and the release of a water-filled syringe held in the patient's hand. RESULTS: Induction times to loss of the eyelash reflex were significantly shorter in the remifentanil than in the fentanyl groups: with propofol 50.7 +/- 13.6s (mean +/- SD) versus 74.9 +/- 27.0s (P < 0.01), with thiopental 42.9 +/- 16.8s versus 77.2 +/- 27.8s (P < 0.01) and with etomidate 54.7 +/- 17.6s versus 72.3 +/- 24.0s (P < 0.05). The times to respiratory arrest or for the syringe to fall were significantly shorter with remifentanil than with fentanyl for propofol and for thiopental, but not for etomidate. In terms of dosages per kg body weight necessary to achieve unresponsiveness, less propofol (-29%, P < 0.05), thiopental (-25%, P < 0.05) or etomidate (-32%, P < 0.01) was necessary with remifentanil than with fentanyl. Haemodynamic responses to tracheal intubation were controlled more effectively with remifentanil. However, within the remifentanil groups, mean arterial pressure significantly decreased during induction: -26% with propofol, -181% with thiopental and -14% with etomidate (all P < 0.01). CONCLUSIONS: During anaesthetic induction, a remifentanil infusion of 0.5 microg kg(-1) min(-1) over 5 min is a suitable alternative to a 1.5 microg kg(-1) bolus dose of fentanyl: induction times are shorter with reduced amounts of propofol, thiopental or etomidate.

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Population cycles that persist in time and are synchronized over space pervade ecological systems, but their underlying causes remain a long-standing enigma. Here we examine the synchronization of complex population oscillations in networks of model communities and in natural systems, where phenomena such as unusual '4- and 10-year cycle' of wildlife are often found. In the proposed spatial model, each local patch sustains a three-level trophic system composed of interacting predators, consumers and vegetation. Populations oscillate regularly and periodically in phase, but with irregular and chaotic peaks together in abundance-twin realistic features that are not found in standard ecological models. In a spatial lattice of patches, only small amounts of local migration are required to induce broad-scale 'phase synchronization, with all populations in the lattice phase-locking to the same collective rhythm. Peak population abundances, however, remain chaotic and largely uncorrelated. Although synchronization is often perceived as being detrimental to spatially structured populations, phase synchronization leads to the emergence of complex chaotic travelling-wave structures which may be crucial for species persistence.

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Anaesthetic management for oocyte retrieval may interfere with the results and success rate of an in vitro fertilization (IVF) program. This study was conducted to compare the effects of two different anaesthetic techniques (general anaesthesia versus sedation) used for oocyte retrieval on IVF outcome. For general anaesthesia we used a combination of remifentanil (Ultiva) with either propofol or isoflurane in hypnotic concentrations. For sedation the protocol included midazolam, diazepam or propofol according to clinical needs. In total, 202 women were enrolled in the study. 96 women opted for sedation and 106 for general anaesthesia. The number of collected oocytes was significantly higher with general anaesthesia (10.54+/-5.43 [mean+/-SD]) than with sedation (6.25+/-3.65, p<0.0001), whereas the number of fertilized oocytes was not different (4.70+/-3.57 vs. 4.23+/-2.90). There were no significant differences in cleavage and pregnancy rates. We therefore believe that remifentanil-based general anaesthesia without nitrous oxide is a suitable alternative to sedation and may be recommended for IVF oocyte retrieval if general anaesthesia is requested.

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Coral reefs are generally considered to be the most biologically productive of all marine ecosystems, but in recent times these vulnerable aquatic resources have been subject to unusual degradation. The general decline in reefs has been greatly accelerated by mass bleaching in which corals whiten en masse and often fail to recover. Empirical evidence indicates a coral reef bleaching cycle in which major bleaching episodes are synchronized with El Niño events that occur every 3-4 years on average. By heating vast areas of the Pacific Ocean, and affecting the Indian and Atlantic Oceans as well, El Niño causes widespread damage to reefs largely because corals are very sensitive to temperature changes. However, mass bleaching events were rarely observed before the 1970s and their abrupt appearance two decades ago remains an enigma. Here we propose a new explanation for the sudden occurrence of mass bleaching and show that it may be a response to the relative increase in El Niño experienced over the last two decades.

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There is no simple explanation for the unusual increase in coral reef bleaching events that have been occurring on a global scale over the last 2 decades. Recent studies focusing on this problem reveal that mass bleaching events have a strong periodic component, arising every 3-4 yr in step with the El Niño climatic phenomenon. To explore this possibility further, we examine a simple oceanographic-ecological model designed to simulate the warm and cool phases of the Pacific Ocean cycle and gauge its effect on local coral reefs. This allows us to identify causes for localized 'hot spots' in the ocean, whose high sea surface temperatures have disastrous consequences for corals. The underlying wave dynamics of the model lead to chaotic oscillations (every 3-4 yr), which help explain the coexistence of both order and irregularity in the dynamics of mass bleaching. The model makes use of a temperature threshold mechanism-a bleaching event is triggered whenever temperature anomalies exceed a critical level. In a variable environment, the threshold mechanism is sensitive to background fluctuations, and their effects are studied by making use of a 'stochastic resonance' formulation. Global climate change and other trends in external background environmental conditions are all shown to strongly influence the distribution of mass coral bleaching events.

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OBJECTIVES: Due to its unique pharmacokinetics, the new esterase-metabolised opioid remifentanil results in rapid post-anesthesia recovery. The aim of this clinical investigation was to compare recovery times after remifentanil anaesthesia in combination with hypnotic concentrations of either propofol or isoflurane. Dosages used in the study protocol were based on recommendations by the pharmaceutical manufacturer. METHODS: Patients (ASA status I-II) scheduled for elective arthroscopy were included in this trial. Without premedication in the morning, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil-infusion (0.5 micrograms/kg/min), followed immediately by propofol (ca. 2 mg/kg). For maintenance of anaesthesia remifentanil (0.25 micrograms/kg/min) was combined with either a propofol infusion of 0.1 mg/kg/min or 0.5 MAC isoflurane (= 0.6 vol. %) in O2/air. Anaesthetic delivery was discontinued simultaneously with termination of surgery and recovery times were recorded. RESULTS: A total of 40 patients were studied at random in two groups of 20 each with comparable demographic data and anaesthetic technique (Tables 1 and 2). In both groups emergence was very rapid. Recovery times were significantly shorter for remifentanil-isoflurane than for remifentanil-propofol (Table 3): spontaneous ventilation 5.1 vs 8.1 min (P < 0.05), extubation 5.5 vs 8.6 min (P < 0.02), post-anaesthesia recovery score > or = 9 of 10 points 6.2 vs 11.3 min (P < 0.01), and arrival at PACU 16.2 vs 19.2 min (P < 0.01). Mild to moderate shivering was noted in 40% of all patients (9 cases following isoflurane, 7 following propofol). CONCLUSIONS: Using the manufacturer's recommended dosages, emergence after remifentanil anaesthesia is more rapid with 0.5 MAC isoflurane than with 0.1 mg/kg/min propofol. These results are most probably due to the different pharmacological properties of both co-anaesthetics, especially the applied dosages, and to different interactions with remifentanil. Present clinical experience suggests that a further dose reduction, especially for propofol, is possible. For both remifentanil groups emergence was remarkably rapid between return of consciousness and the awake state (on-off phenomenon), which might contribute to post-anaesthesia safety.

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A 73-year-old woman developed a lingual infarction, Raynaud's phenomenon, cutaneous lesions, pancytopenia, and pleuritis. Serologic studies supported a diagnosis of systemic lupus erythematosus (SLE), and anticardiolipin antibodies were detected in significant titers. This is the first reported case of SLE presenting with an infarction of the tongue.

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Percutaneous cholecystostomy can be a useful technique for the ill, elderly, or high-risk patient, since he or she is spared open surgery. We used it successfully in a medically unstable woman with acute acalculous cholecystitis. Her drainage catheter, often the source of complications with the procedure, may have been removed too early: A small asymptomatic subdiaphragmatic fluid collection and ileus developed. However, both resolved in 48 hours.

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