Little Evidence Of Reduction Research Articles

Reanalysis indicates little evidence of reduction in eagle mortality rate by automated curtailment of wind turbines

Abstract Unintended consequences of renewable energy development include collision‐caused deaths of birds and bats. Energy companies may risk prosecution if protected species are among the casualties. Shutting down turbines during high collision‐risk conditions could reduce mortality rates, and several companies are developing systems to identify such conditions. A recent peer‐reviewed article published in the Journal of Applied Ecology reported a remarkable ‘82% (75%–89%) reduction in the fatality rate’ of eagles at a wind energy facility due to a device marketed as Identiflight®—remarkable because of the impressive effect size and the extremely high level of precision. We show that reported results stem from four major errors, which, when corrected, give an unremarkable estimate of 50% (−159%, 89%) reduction (or possible increase) in the fatality rate. The errors include the following: (i) Ignoring annual variation. They compare the average number of eagle fatalities over 4 years before activation of Identiflight® to the number in a single year after, ignoring annual variation in fatalities. (ii) Unfounded causal inference. Lack of replication (one treatment year at one site) is ignored, leading to unwarranted causal inference. (iii) Inflated effect size. Effect size is inflated by assuming (without providing evidence) that the difference in fatality relative to the mean at a neighbouring site would be exactly repeated at the treatment site. Furthermore, the observed difference in fatalities at the control site depends strongly on the arbitrarily chosen date distinguishing the ‘Before’ and ‘After’ periods, yielding unreliable results. (iv) Inconsistency of data. It is unclear why 7 of 42 reported eagle fatalities were not included in the data analyzed, potentially further inflating the estimated effect size. Synthesis and applications. The recent claim, published in the Journal of Applied Ecology, that ‘Eagle fatalities are reduced by automated curtailment of wind turbines’ is not supported by the data but stems from errors that led to strongly overstated effect size and precision, and unfounded inference. In theory, automated curtailment has obvious potential for reducing eagle fatalities, but several more years of data at several locations and appropriate statistical analyses will be required to evaluate its effectiveness and to inform management prescriptions involving this technology.

Impact of Lean Tools in the Supply Chain: Pharmaceutical Industry Perspective

The aim of this paper is to identify the impact of the application of lean tools in the pharmaceutical supply chain (PSC) through a literature review. Supply chain inefficiencies before and during the COVID 19 pandemic, most applied tools, and lean improvements found in the PSC are identified. Databases such as Scopus and Proquest were used to collect the peer-reviewed articles to be studied. Results show the most frequent inefficiencies in the supply chain are found in operating costs, scrap rates, delivery times, and drug shortages. The improvements identified can be summarized in three factors: cost reduction, time reduction, and improvement in the management of activities. The most studied tools are Kaizen, Kanban, Total Quality Management (TQM), and Value Stream Mapping (VSM). Literature reveals that lean tools have a significant impact on quality improvement of information, products and/or services, as well as on the reduction or elimination of activities that do not generate value; in addition, there is little evidence of reduction of unnecessary movements of workers. The value of this paper addresses the impact of the pandemic on PSC, describing the versatility that each of the tools had in their role to reduce lean wastes. The versatility allows to identify which tool may be available according to the need of the practitioner.

New insights about vaccine effectiveness: Impact of attenuated PRRS-strain vaccination on heterologous strain transmission

Vaccination is the main tool for controlling infectious diseases in livestock. Yet current vaccines only provide partial protection raising concerns about vaccine effectiveness in the field.Two successive transmission trials were performed involving 52 pigs to evaluate the effectiveness of a Porcine Reproductive and Respiratory Syndrome (PRRS) vaccinal strain candidate against horizontal transmission of a virulent heterologous strain. PRRS virus, above the specified limit of detection, was observed in serum and nasal secretions for all but one pig (the exception only tested positive for serum), indicating that vaccination did not protect pigs from becoming infected and shedding the heterologous strain. However, vaccination delayed the onset of viraemia, reduced the duration of shedding and significantly decreased viral load throughout infection. Serum antibody profiles indicated that 4 out of 13 (31%) vaccinates in one trial had no serological response (NSR).A Bayesian epidemiological model was fitted to the data to assess the impact of vaccination and presence of NSRs on PRRS virus transmission dynamics. Despite little evidence for reduction in the transmission rate, vaccinated animals were on average slower to become infectious, experienced a shorter infectious period and recovered faster. The overall PRRSV transmission potential, represented by the reproductive ratio R0 was lower for the vaccinated animals, although there was substantial overlap in the credibility intervals for both groups. Model selection suggests that transmission parameters of vaccinated pigs with NSR were more similar to those of unvaccinated animals. The presence of NSRs in a population, however, seemed to only marginally affect the transmission dynamics.The results suggest that even when vaccination can’t prevent infection, it can still have beneficial impacts on the transmission dynamics and contribute to reducing a herd’s R0. However, biosecurity and other measures need to be considered to decrease contact rates and lower R0 below 1.

A nationwide survey of hospital-based thalassemia patients and standards of care and a preliminary assessment of the national prevention program in Sri Lanka.

ObjectivesOur aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme.MethodsThis cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records.ResultsWe collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45–55, with little evidence of reduction over 19 years.ConclusionsCentral coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

BackgroundSchistosoma mansoni is a parasite of profound medical importance. Current control focusses on mass praziquantel (PZQ) treatment of populations in endemic areas, termed Preventative Chemotherapy (PC). Large-scale PC programmes exert prolonged selection pressures on parasites with the potential for, direct and/or indirect, emergence of drug resistance. Molecular methods can help monitor genetic changes of schistosome populations over time and in response to drug treatment, as well as estimate adult worm burdens through parentage analysis. Furthermore, methods such as in vitro drug sensitivity assays help phenotype in vivo parasite genotypic drug efficacy.MethodsWe conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ.ResultsWe demonstrated that there were individual parasites with reduced PZQ susceptibility in the 2010 collections, as evidenced by our in vitro larval behavioural phenotypic assay. There was no evidence, however, that miracidia showing phenotypically reduced susceptibility clustered together genetically. Molecular analysis also demonstrated a significant reduction of adult worm load over time, despite little evidence of reduction in parasite infection intensity, as measured by egg output. Genetic diversity of infections did not reduce over time, despite changes in the genetic composition of the parasite populations.ConclusionsGenotypic and phenotypic monitoring did not indicate a selective sweep, as may be expected if PZQ treatment was selecting a small number of related “resistant” parasites, but there was evidence of genetic changes at the population level over time. Genetic data were used to estimate adult worm burdens, which unlike parasite infection intensity, showed reductions over time, suggesting the relaxation of negative density-dependent constraints on parasite fecundity with PZQ treatment. We thereby demonstrated that density-dependence in schistosome populations may complicate evaluation and monitoring of control programmes.

Secondary‐volatiles linked metallic iron in eucrites: The dual‐origin metals of Camel Donga

AbstractThe unique occurrence of abundant (~1 vol%) near‐pure‐Fe metal in the Camel Donga eucrite is more complicated than previously believed. In addition to that component of groundmass metal, scattered within the meteorite are discrete nodules of much higher kamacite abundance. We have studied the petrology and composition of two of these nodules in the form of samples we call CD2 and CD3. The nodules are ovoids 11 (CD2) to 15 (CD3) mm across, with metal, or inferred preweathering metal, abundances of 12–17 vol% (CD2 is unfortunately quite weathered). The CD3 nodule also includes at its center a 5 mm ovoid clumping (6 vol%) of F‐apatite. Both nodules are fine‐grained, so the high Fe metal and apatite contents are clearly not flukes of inadequate sampling. The metals within the nodules are distinctly Ni‐rich (0.3–0.6 wt%) compared to the pure‐Fe (Ni generally 0.01 wt%) groundmass metals. Bulk analyses of three pieces of the CD2 nodule show that trace siderophile elements Ir, Os, and Co are commensurately enriched; Au is enriched to a lesser degree. The siderophile evidence shows the nodules did not form by in situ reduction of pyroxene FeO. Moreover, the nodules do not show features such as silica‐phase enrichment or pyroxene with reduced FeO (as constrained by FeO/MgO and especially FeO/MnO) predicted by the in situ reduction model. The oxide minerals, even in groundmass samples well away from the nodules, also show little evidence of reduction. Although the nodule boundaries are generally sharp, groundmass‐metal Ni content is anti‐correlated with distance from the CD3 nodule. We infer that the nodules represent materials that originated within impactors into the Camel Donga portion of the eucrite crust, but probably were profoundly altered during later metamorphism/metasomatism. Origin of the pure‐Fe groundmass metal remains enigmatic. In situ reduction probably played an important role, and association in the same meteorite of the Fe‐nodules is probably significant. But the fluid during alteration was probably not (as previously modeled) purely S and O, of simple heat‐driven internal derivation. We conjecture a two‐stage metasomatism, as fluids passed through Camel Donga after impact heating of volatile‐rich chondritic masses (survivors of gentle accretionary impacts) within the nearby crust. First, reduction to form troilite may have been triggered by fluids rich in S2 and CO (derived from the protonodules?), and then in a distinct later stage, fluids were (comparatively) H2O‐rich, and thus reacted with troilite to form pure‐Fe metal along with H2S and SO2. The early eucrite crust was in places a dynamic fluid‐bearing environment that hosted complex chemical processes, including some that engendered significant diversity among metal+sulfide alterations.

Examination of England's New Medicine Service (NMS) of complex health care interventions in community pharmacy.

Community pharmacies are increasingly commissioned to deliver new, complex health interventions in response to the growing demands on family doctors and secondary health care services. Little is known about how these complex interventions are being accommodated and translated into the community pharmacy setting and whether their aims and objectives are realized in practice. The New Medicine Service (NMS) is a complex medicine management intervention that aims to support patients' adherence to newly prescribed medicines for a long-term condition. This study explores the recent implementation of the NMS in community pharmacies across England. It also seeks to understand how the service is becoming manifest in practice and what lessons can be learned for future service implementation. Structured, organizational ethnographic observations and in situ workplace interviews with pharmacists and support staff were undertaken within 23 English community pharmacies. Additionally, one-to-one, semi-structured interviews were carried out with 47 community pharmacists and 11 general practitioners (GPs). Observational and interview data were transcribed and analyzed thematically and guided by Damschroder's consolidated framework for implementation research. The NMS workload had been implemented and absorbed into pharmacists' daily routines alongside existing responsibilities with no extra resources and little evidence of reduction in other responsibilities. Pharmacists were pragmatic, simplifying, and adapting the NMS to facilitate its delivery and using discretion to circumvent perceived non-essential paperwork. Pharmacist understanding of the NMS was found to impact on what they believed should be achieved from the service. Despite pharmacists holding positive views about the value of the NMS, not all were convinced of its perceived benefits and necessity, with reports that many consultations did not identify any problems with the patients' medicines. GPs were generally supportive of the initiative but were unaware of the service or potential benefits. Poorly developed existing pharmacist-GP relationships impeded implementation. This study identifies the multifaceted and complex processes involved in implementing a new community pharmacy service in England. Community pharmacy workflow, infrastructure, and public and professional relationships all affect NMS implementation. Greater prior engagement with the pharmacy workforce and GPs, robust piloting and a phased rollout together with ongoing support and updates, are potentials strategies to ensure future implementation of pharmacy services meet their intended aims in practice.

Primates

Primates

Prevalence and trajectory of disease- and treatment-related symptom burden in patients with multiple myeloma undergoing induction therapy.

e19627 Background: Patients with multiple myeloma (MM) undergoing induction therapy experience both disease- and therapy-related symptoms. This study selectively focused on the trajectory of pain, fatigue, numbness and bone aches from patient-reported outcome. Methods: MM patients (N=62) repeatedly rated symptoms via the M. D. Anderson Symptom Inventory (MDASI) (twice a week for 12 weeks, then weekly for 6 weeks). Ordinal regression analysis was used to describe symptom trajectories across time. Group-based trajectory modeling was used 1) to estimate the proportion of MM patients belonging to high, medium or low group by symptom severity; and 2) to examine the patterns of each group derived for each symptom. Results: During induction period, fatigue was persistently the most severe symptom, while therapy-induced neuropathy (MDASI numbness item) increased significantly from baseline (P=.0008). Group-based trajectory modeling resulted in 3 groups as the best model fit for 4 symptoms. The proportions of patients categorized as having high, medium or low symptom severity, respectively, were: for pain, 27%, 41% and 32%; for bone ache, 22%, 43% and 35%; for numbness, 22%, 48% and 30%; for fatigue, 28%, 58% and 14%. For pain, we observed a significant linear increased trend in the medium group (P<.001). For fatigue, bone ache and numbness, the medium and low groups exhibited only a slight change in slope, while the high symptom group showed a significant initial increase followed by a decrease trend (all quadratic trends, P<.001). Other than baseline performance status (P<.01), no clinical or patient factor was related to group membership. Conclusions: The majority of patients reported moderate or greater fatigue, pain and bone aches throughout the induction treatment, with little evidence of reduction, while numbness/tingling dramatically increased over time. We also observed that some MM patients persistently reported low symptom burden compared to others, despite similar disease burden and therapy. These results warrant further translational studies to identify biomarker(s) related to high symptom burden, so as to guide personalized patient care during standard induction therapy.

Nebulisers or spacers for the administration of bronchodilators to those with asthma attending emergency departments?

Systematic reviews and national guidelines conclude that the nebulised route of administration of bronchodilators has no advantage over the use of a spacer in moderately severe exacerbations of asthma. Whether this recommendation is implemented and whether it might affect use of staff time is unknown. To determine the current method of administration of bronchodilators to those with non-life-threatening asthma attending emergency departments (ED) in London, UK and to monitor the implementation of a new policy to administer bronchodilators by spacers in one ED with a special reference to the time taken by nurses to administer the therapy by two different routes. Thirty-five EDs in Greater London were surveyed regarding their current practice. A time and motion study was then undertaken in one department observing nurses administering bronchodilators in the 3 weeks before and 3 weeks after a departmental policy change to favour the use of spacer devices rather than nebulisers. The majority of EDs (94.3%) in Greater London were using the nebulised route of administering bronchodilators to the majority of their adult patients. Spacers were more commonly used for the treatment of children (60.3% of departments using spacers and nebulisers or spacers alone). Over half of the hospitals surveyed (51.4%) were unaware that the British Guidelines on Asthma Management suggested that outcomes were the same and that there were potential advantages in the use of a spacer for both adults and children. Time and motion studies showed that the use of a spacer took no more nursing time than administration of the bronchodilator via a nebuliser; in fact treatment and set-up time were considerably lower for spacers. Spacer administration of bronchodilators to those with asthma attending EDs utilises less treatment time than use of a nebuliser. A survey of EDs in Greater London has shown that despite guideline conclusions there appears to be little evidence of reduction in use of nebulisers; a fear that use of alternatives might take nurses longer is not supported by this study.

Human bocavirus in swedish children 2004 to 2005

Systematic reviews and national guidelines conclude that the nebulised route of administration of bronchodilators has no advantage over the use of a spacer in moderately severe exacerbations of asthma. Whether this recommendation is implemented and whether it might affect use of staff time is unknown.To determine the current method of administration of bronchodilators to those with non-life-threatening asthma attending emergency departments (ED) in London, UK and to monitor the implementation of a new policy to administer bronchodilators by spacers in one ED with a special reference to the time taken by nurses to administer the therapy by two different routes.Thirty-five EDs in Greater London were surveyed regarding their current practice. A time and motion study was then undertaken in one department observing nurses administering bronchodilators in the 3 weeks before and 3 weeks after a departmental policy change to favour the use of spacer devices rather than nebulisers.The majority of EDs (94.3%) in Greater London were using the nebulised route of administering bronchodilators to the majority of their adult patients. Spacers were more commonly used for the treatment of children (60.3% of departments using spacers and nebulisers or spacers alone). Over half of the hospitals surveyed (51.4%) were unaware that the British Guidelines on Asthma Management suggested that outcomes were the same and that there were potential advantages in the use of a spacer for both adults and children. Time and motion studies showed that the use of a spacer took no more nursing time than administration of the bronchodilator via a nebuliser; in fact treatment and set-up time were considerably lower for spacers.Spacer administration of bronchodilators to those with asthma attending EDs utilises less treatment time than use of a nebuliser. A survey of EDs in Greater London has shown that despite guideline conclusions there appears to be little evidence of reduction in use of nebulisers; a fear that use of alternatives might take nurses longer is not supported by this study.

Dose– and time–response relationships for lethal mutations and chromosomal instability induced by ionizing radiation in an immortalized human keratinocyte cell line

Purpose : To investigate the relationship between two well-established delayed effects of ionizing radiation, experiments were conducted to determine the induction and expression of lethal mutations (delayed reproductive death) and chromosomal instability with respect to dose and time in a human immortalized keratinocyte cell line. Methods : HPV-G cells were γ- or α -irradiated and maintained in culture for up to 72 population doublings. At intervals, measurements were made of cloning efficiency and the cells examined for apoptosis and cytogenetic aberrations. Results : The descendants of cells surviving 1 or 3 Gy γ-irradiation, but not 0.5 Gy γ-irradiation, exhibited a reduced colony-forming efficiency. The reduction persisted at a constant rate of 15–20% clonogenic cell loss per population doubling for up to 72 population doublings. Apoptosis was demonstrated in all colonies in the 1 and 3 Gy groups at 30 and 72 population doublings post-irradiation but not in the 0.5 Gy group. A significant persistent reduction in colony-forming ability (~80%) was demonstrated in the progeny of cells irradiated with 0.5 Gy α -particles. After 30 population doublings, the proportion of chromosomally aberrant cells was significantly greater than control values for all doses of both high- and low-LET radiations. The major cytogenetic aberrations (chromatid breaks, chromosome fragments and minutes) were consistent with the transmission of chromosomal instability. The expression of instability declined between 30 and 72 population doublings in the 0.5Gy and 3 Gy gamma-irradiation groups, but persisted up to 72 population doublings in the 1 Gy group. The expression of chromosomal instability was greater in the descendants of alpha-irradiated cells and showed little evidence of reduction with time. Conclusions : Unstable aberrations characteristic of radiation-induced chromosomal instability may commonly result in apoptosis and account for a component of the delayed reproductive death/lethal mutation phenotype in HPV-G cells. However, the absence of lethal mutations in the descendants of 0.5 Gy γ-irradiated cells indicates a low-LET threshold effect for this particular endpoint. Overall, and particularly at low doses, there is no direct correlation between the two endpoints, indicating the absence of a simple relationship between these manifestations of radiation-induced genomic instability.

Detection of the impact of predation by migratory shorebirds:an experimental test in the Fraser River estuary, British Columbia (Canada)

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 144:23-40 (1996) - doi:10.3354/meps144023 Detection of the impact of predation by migratory shorebirds: an experimental test in the Fraser River estuary, British Columbia (Canada) Sewell MA Exclosure experiments are commonly used in marine soft sediments to examine changes in invertebrate density caused by shorebird predation. However, many of these exclosure experiments do not incorporate the spatial variability of the invertebrate prey in their design and/or analysis. This paper uses a short-term exclosure experiment and random sampling (Before/After predation) to assess reductions in invertebrate densities by western sandpiper Calidrismauri on the Fraser River estuary, British Columbia, Canada. During the spring >1 million western sandpiper stop over at the Fraser River estuary on their northward migration to breeding grounds in Alaska. Exclosure experiments and Before/After sampling were conducted at 3 sites on the Fraser River estuary that differed in their sediment characteristics and in their use for feeding by western sandpiper. An examination of cage effects showed that there were no alterations to sediment composition caused by the exclosure cage. However, there were changes in invertebrate numbers in the exclosure cage irrespective of shorebird predation. In particular, mobile invertebrates, such as gastropods and crustaceans, migrated into or out of the exclosure cages during the experiment. Overall, there was little evidence for reduction in invertebrate numbers caused by western sandpiper predation. In the exclosure experiment a significant decline was observed in the phyllodocid polychaete Eteone spp., but at a site with little evidence of shorebird predation. Before/After sampling showed some declines in invertebrate numbers, but this could reflect patchiness in invertebrate distributions rather than the direct action of predation. The use of statistical designs for detecting environmental impacts (e.g. BACI) is suggested for future studies of shorebird predation as they allow for the spatial and temporal variability of the invertebrate prey to be considered concomitant with the impact of the shorebird predator. General problems of sampling with sediment cores, high sample variance, and the reduced power of experimental tests need to be considered in future research on the interactions of shorebird predators and their marine invertebrate prey. Shorebird predation · Western sandpiper · Calidrismauri · Soft sediments · Exclosure experiment Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 144. Publication date: December 05, 1996 Print ISSN:0171-8630; Online ISSN:1616-1599 Copyright © 1996 Inter-Research.

Effect of trifluoroacetic acid on the reduction of disulfide bridges in peptides analyzed by fast‐atom bombardment mass spectrometry

Some of the factors that influence the reduction of disulfide-containing peptides under fast-atom bombardment have been investigated using two neurohormonal peptides that include disulfide bridges in their structures. Deaminoarginine-vasopressin (DAVP) and arginine-vasopressin (AVP) have been analyzed as their acetate and trifluoroacetate salts. Results obtained in a thioglycerol matrix indicate that the peptides analyzed as their acetate salts are completely reduced under bombardment, whereas the trifluoroacetate salts show little evidence of reduction. Addition of trifluoroacetic acid to the acetate sample prior to bombardment inhibits reduction whereas addition after bombardment shows no effect on the reduction, thereby indicating the irreversibility of the process. Time-monitoring experiments conducted with the acetate salts of DAVP and AVP in common matrices such as thioglycerol, dithiothreitol + diethioerythritol, glycerol, hydroxyethyldisulfide and nitrobenzyl-alcohol demonstrate an important effect of the chemical nature of the matrix on reduction. In matrices containing thiol groups, the reduction is extensive, whereas it is almost suppressed in matrices such as hydroxyethyldisulfide and nitrobenzylalcohol. However, the addition of trifluoroacetic acid to all of these matrices essentially eliminates reduction and provides measured isotopic peak ratios that are in agreement with theoretically calculated values for these peptides.

Investigation of the determinative state of the mouse inner cell mass

ABSTRACTInner cell masses (ICMs) were dissected from and day mouse blastocysts and inserted into empty zonae before transfer to the oviducts of pseudopregnant mice. The ICMs survived in the oviduct for at least 2 days with little evidence of reduction in cell number. After 1 day, isolated day ICMs were still viable, since they could form chimaeras when injected into day blastocysts. However, no evidence of trophoblast formation could be detected in any of the isolated ICMs, despite exposure of some of their cells to ‘outside’ conditions. This is further evidence that ICM cells, although not overtly differentiated, are determined by days. Although no trophoblast was formed, day ICMs formed an outer endoderm layer after 1 day in the oviduct, as judged by light and electron microscopical evidence. It is suggested that cell position may be important in endoderm differentiation.

THE MECHANISM OF VOLUNTARY MUSCULAR FATIGUE

THE MECHANISM OF VOLUNTARY MUSCULAR FATIGUE

The Mechanism of Voluntary Muscular Fatigue

The Mechanism of Voluntary Muscular Fatigue