Major Triggering Factor Research Articles

SSNM-based rationale of fertilizer use in perennial crops : A review

Behaviour of crops and soils due to non-redressal of spatial variability in soil properties is not expressed uniformly within bigger orchard/field which has been the major triggering factor for not able to break yield barrier through conventional nutrient management strategy. Better response of site specific nutrient management (SSNM) over recommended doses of fertilizers (RDF) including those of farmers’ usual fertilizer practices (FFP) signals a wake-up call to address the fertilizer requirements on the principles of SSNM, if the full potential productivity of perennial crops has to be realized and sustain on any given soil type. The SSNM also warrants to tailor the fertilizer application on the basis of spatial variation in soil fertility and tree canopy size within an orchard/field through variable rate fertilizer application to minimize the gap between actual and potential productivity of crops. Application of geospatial tools like GPS and GIS coupled with DRIS- based nutrient diagnostics has substantially aided in developing rationale of fertilizer use using SSNM concept in crops like citrus, avocado, coconut, olive etc. which could well be expanded to other perennial crops.

Brain-kidney crosstalk.

Encephalopathy and altered higher mental functions are common clinical complications of acute kidney injury. Although sepsis is a major triggering factor, acute kidney injury predisposes to confusion by causing generalised inflammation, leading to increased permeability of the blood–brain barrier, exacerbated by hyperosmolarity and metabolic acidosis due to the retention of products of nitrogen metabolism potentially resulting in increased brain water content. Downregulation of cell membrane transporters predisposes to alterations in neurotransmitter secretion and uptake, coupled with drug accumulation increasing the risk of encephalopathy. On the other hand, acute brain injury can induce a variety of changes in renal function ranging from altered function and electrolyte imbalances to inflammatory changes in brain death kidney donors.

Do Functional Problems and Neighborhood Disturbances in and around the Home Trigger Injuries?

The study has tried to identify whether poor self-rated health and home and neighbourhood environmental problems trigger injuries. The study used data from the Life & Health year 2008 survey, a postal questionnaire administered by Statistics Sweden in five administrative regions in central Sweden (Uppsala, S?dermanland, ?rebro, Varmland and V?stmanland). A random sample of 1,060,032 respondents aged 18 - 79 years had participated in the study. ?rebro and Varmland region had the highest proportions of injuries. People at their age between 18 to 24 years—males—tobacco and alcohol addicted had the highest proportions of injuries. Environmental factors such as disturbances in and around home had emerged as major triggering factors for injuries. Physical functional problems such as problem of buying own food, cooking, dressing-up and walking had been emerged as very strong predicting factors of injuries. Policy makers in Sweden could identify the poor neighborhood, disturb living condition through the housing companies and the cooperative housing societies to control injuries and promote safety.

Regional scale rainfall- and earthquake-triggered landslide susceptibility assessment in Wudu County, China

Wudu County in northwestern China frequently experiences large-scale landslide events. High-magnitude earthquakes and heavy rainfall events are the major triggering factors in the region. The aim of this research is to compare and combine landslide susceptibility assessments of rainfalltriggered and earthquake-triggered landslide events in the study area using Geographical Information System (GIS) and a logistic regression model. Two separate susceptibility maps were produced using inventories reflecting single landslide-triggering events, i.e., earthquakes and heavy rain storms. Two groups of landslides were utilized: one group containing all landslides triggered by extreme rainfall events between 1995 and 2003 and the other group containing slope failures caused by the 2008 Wenchuan earthquake. Subsequently, the individual maps were combined to illustrate the locations of maximum landslide probability. The use of the resulting three landslide susceptibility maps for landslide forecasting, spatial planning and for developing emergency response actions are discussed. The combined susceptibility map illustrates the total landslide susceptibility in the study area.

Serum IgA reactivity against GroEL ofStreptococcus sanguinisand human heterogeneous nuclear ribonucleoprotein A2/B1 in patients with Behçet disease

Infectious agents, especially Streptococcus sanguinis and herpes simplex virus, have long been postulated as major triggering factors for Behçet disease (BD).To identify an anti-S. sanguinis antigen reacting with serum IgA antibody in patients with BD.We detected a target protein by proteomics analysis and evaluated serum IgA reactivity of 100 patients with BD against the identified streptococcal target protein and human heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1. Homologous epitope sequences between the streptococcal target protein and human hnRNP A2/B1 were also evaluated.Four protein bands were detected by immunoprecipitation, and chaperonin GroEL was identified by a proteomics analysis. Reactivity of serum IgA against recombinant S. sanguinis GroEL was detected in 77 of 100 patients with BD (77%) and in 21 of 70 healthy controls (30%). In addition, reactivity of serum IgA against human recombinant hnRNP A2/B1 was seen in 79 of 100 patients with BD (79%) and in eight of 70 healthy controls (11%). Among the eight distinctive epitopes with significant homology between S. sanguinis GroEL and human hnRNP A2/B1, the serum IgA reactivity of patients with BD was markedly higher with epitope 3 (hnRNP A2/B1 peptide 33-46 and GroEL peptide 57-70) and epitope 6 (hnRNP A2/B1 peptide 177-188 and GroEL peptide 347-358).We identified an S. sanguinis GroEL protein as a target of serum anti-S. sanguinis IgA antibody reactivity in patients with BD. In addition, patients with BD exhibited serum IgA reactivity against homologous epitope regions between S. sanguinis GroEL and human hnRNP A2/B1.

Nuclear factor (NF)‐κB and its associated pathways are major molecular regulators of blood‐induced joint damage in a murine model of hemophilia

The present study was designed to investigate the molecular signaling events from onset of bleeding through the development of arthropathy in a murine model of hemophilia A. A sharp-injury model of hemarthrosis was used. A global gene expression array on joint-specific RNA isolated 3 h post-injury revealed nuclear factor-kappa B (NF-κB) as the major transcription factor triggering inflammation. As a number of genes encoding the cytokines, growth factors and hypoxia regulating factors are known to be activated by NF-κB and many of these are part of the pathogenesis of various joint diseases, we reasoned that NF-κB-associated pathways may play a crucial role in blood-induced joint damage. To further understand its role, we screened NF-κB-associated pathways between 1 h to 90 days after injury. After a single articular bleed, distinct members of the NF-κB family (NF-κB1/NF-κB2/RelA/RelB) and their responsive pro-inflammatory cytokines (IL-1β/IL-6/IFNγ/TNFα) were significantly up-regulated (> 2 fold, P < 0.05) in injured vs. control joints at the various time-points analyzed (1 h/3 h/7 h/24 h). After multiple bleeds (days 30/60/75/90), there was increased expression of NF-κB-associated factors that contribute to hypoxia (HIF-1α, 3.3-6.5 fold), angiogenesis (VEGF-α, 2.5-4.4 fold) and chondrocyte damage (matrix metalloproteinase-13, 2.8-3.8 fold) in the injured joints. Micro RNAs (miR) that are known to regulate NF-κB activation (miRs-9 and 155), inflammation (miRs-16, 155 and 182) and apoptosis (miRs-19a, 155 and 186) were also differentially expressed (-4 to +13-fold) after joint bleeding, indicating that the small RNAs could modulate the arthropathy phenotype. These data suggest that NF-κB-associated signaling pathways are involved in the development of hemophilic arthropathy.

Influence of simethicone and alverine on stress-induced alterations of colonic permeability and sensitivity in rats: beneficial effect of their association

Alverine, an antispasmodic agent for the treatment of irritable bowel syndrome (IBS), may be combined with simethicone, a protective agent of the mucosa. Stress is a major factor triggering abdominal pain in IBS and causing hypersensitivity to colonic distension in animals through an increased colonic permeability. The antinociceptive effects of alverine and simethicone, separately or in association, were evaluated on stress-induced colonic hypersensitivity to distension in rats. The influence of simethicone on altered permeability was also tested. Groups of 8-10 female adult Wistar rats (200-250 g) housed individually were used. Gut paracellular permeability was evaluated after 2 h of partial restraint stress using oral gavage with ⁵¹Cr-EDTA and 24 h of urine collection. The number of abdominal cramps during colonic distension was evaluated in animals equipped with electrodes on their abdominal striated muscles. At 200 mg/kg p.o. twice a day, but not at lower doses, simethicone reduced stress-induced increase of colonic permeability and hypersensitivity to distension. Administered alone at 10 mg/kg p.o., alverine also reduced stress-induced hypersensitivity to distension; lower doses were inactive. However, alverine administered at an inactive dose with simethicone suppressed stress-induced hypersensitivity to distension. We conclude that both simethicone and alverine have visceral antinociceptive effects by two different mechanisms and that simethicone exerts a potentiating effect on the antinociceptive action of alverine.

Immune disorders and its correlation with gut microbiome.

Allergic disorders such as atopic dermatitis and asthma are common hyper-immune disorders in industrialized countries. Along with genetic association, environmental factors and gut microbiota have been suggested as major triggering factors for the development of atopic dermatitis. Numerous studies support the association of hygiene hypothesis in allergic immune disorders that a lack of early childhood exposure to diverse microorganism increases susceptibility to allergic diseases. Among the symbiotic microorganisms (e.g. gut flora or probiotics), probiotics confer health benefits through multiple action mechanisms including modification of immune response in gut associated lymphoid tissue (GALT). Although many human clinical trials and mouse studies demonstrated the beneficial effects of probiotics in diverse immune disorders, this effect is strain specific and needs to apply specific probiotics for specific allergic diseases. Herein, we briefly review the diverse functions and regulation mechanisms of probiotics in diverse disorders.

Mechanisms Underlying the Osteo- and Adipo-Differentiation of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSCs) are considered a promising cell source for regenerative medicine, because they have the potential to differentiate into a variety of lineages among which the mesoderm-derived lineages such adipo- or osteogenesis are investigated best. Human MSCs can be harvested in reasonable to large amounts from several parts of the patient's body and due to this possible autologous origin, allorecognition can be avoided. In addition, even in allogenic origin-derived donor cells, hMSCs generate a local immunosuppressive microenvironment, causing only a weak immune reaction. There is an increasing need for bone replacement in patients from all ages, due to a variety of reasons such as a new recreational behavior in young adults or age-related diseases. Adipogenic differentiation is another interesting lineage, because fat tissue is considered to be a major factor triggering atherosclerosis that ultimately leads to cardiovascular diseases, the main cause of death in industrialized countries. However, understanding the differentiation process in detail is obligatory to achieve a tight control of the process for future clinical applications to avoid undesired side effects. In this review, the current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.

Evaluating triggering and causative factors of landslides in Lawnon River Basin, Taiwan

This study evaluates triggering and causative factors of landslides by comparing their occurrence in the Lawnon River Basin prior to and after rainfall and earthquake events over a five-year period (2005–2009). The landslide ratio in the study area was low (less than 4%) before 2007, and significantly increased in the wake of Typhoon Morakot in 2009. The high accumulation of rainfall was the major triggering factor. In addition, the major seismic activity of March 4, 2008 also contributed to landslide occurrence. The combined influence of rainfall and the earthquake is evaluated based on multi-variable regression analysis. Though no significant co-seismic landslides were found after the March 4, 2008 earthquake, its influence on slope stability has been observed from the apparent growth of landslide ratio in the four rainfall events following the quake. Causative factors include the higher landslide ratios occurring in sedimentary rock zones (especially sandstone formations with intercalations of shale), and dip slopes, which are demonstrably prone to plane failures.

Hydrological and hydrochemical processes observed during a large‐scale infiltration experiment at the Super‐Sauze mudslide (France)

AbstractRainfall is one of the major triggering factors of landslides, and its pattern controls their temporal behaviour. Characterization of the groundwater processes and possible preferential infiltration of rainfall is necessary, challenging and very relevant for landslide hazard analysis. The objective of this paper is to identify the groundwater dynamics (matrix flow and preferential flow) within highly heterogeneous and fissured reworked black marl material, using a large‐scale infiltration test. The artificial rainfall experiment over a 100 m2 infiltration plot monitored with several hydrological, hydrochemical and geophysical equipments was carried out on the Super‐Sauze mudslide (South French Alps). High resolution groundwater and water quality measurements were collected. Artificial rainfall was applied over a period of 14 days. Conservative tracers (Br− and Cl−) were used successively during the infiltration period. The mean rainfall intensity was 8·5 mm h−1 with a mean tracer concentration of 100 mg l−1. The hydrodynamic and hydrochemical responses of the tracing experiments allowed us to get a new insight into: (1) the horizontal and vertical variability of the rain infiltration in unstable black marl hillslopes; (2) the effect of shallow fissuration on the groundwater recharge; (3) the role of piston flow on the rate of water level changes and the increase of pore water pressures and (4) the effect of material heterogeneity in the development of preferential water flows and local perched water tables. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Application of geophysical measurements for assessing the role of fissures in water infiltration within a clay landslide (Trièves area, French Alps)

AbstractRainfall and its consequences are usually considered as the major factor triggering slope instabilities within clay deposits. The link between rainfall, water infiltration and landslide activity may be complex, and comprehensive sets of data are still necessary to understand how water infiltrates in cohesive material. On unstable slopes made of fine‐grained sediments, gravitational deformation generates superficial shear ruptures and tension fissures whose continuous opening could be amplified by shrinkage during dry periods. This fissure network at the surface can be very dense and strongly controls the water infiltration process. However, it remains difficult to assess the fissure evolution at depth and its eventual relationship with shallow slip surfaces. This work presents the results of a geophysical study which aimed to characterize the fissures that are observed along the unstable clay slopes of the Trièves area (French Alps). The site was first investigated combining geomorphological analysis, drilling, borehole logging, geotechnical tests and geophysical experiments. This investigation evidenced the presence of at least three rupture surfaces (at 5, 10–15 and 42 m) with a water flow at the second one. In a second step, permanent instruments were installed (piezometers and soil water content probes). Results indicate high water infiltration velocities, down to the water table located at 2·5 m depth, that are likely to be linked with sub‐vertical preferential paths, such as fissures. Geophysical parameters (electrical resistivity, S‐wave velocities and Rayleigh waves attenuation) were monitored. Geophysical results suggest that fissures are permanently open, that they serve as preferential infiltration paths, and that they can reach, at least, a depth of 2 m. The methods employed in this research put forward that the system of imbricated fissures drains water from the surface down to the shallow slip surfaces at 5 and 10–15 m. This work highlights the role of fissures network in water infiltration in the numerous clay landslides of the Trièves area. Copyright © 2011 John Wiley &amp; Sons, Ltd.

Serum Adipocyte Fatty Acid-Binding Protein Is Associated Independently with Vascular Inflammation: Analysis with18F-Fluorodeoxyglucose Positron Emission Tomography

The inflammatory status of atherosclerotic lesions is a major factor triggering acute cardiovascular events. Growing evidence has shown that adipocyte fatty acid-binding protein (A-FABP) has an important role in the development of atherosclerosis. The objective of the study was to determine the association between circulating A-FABP levels with vascular inflammation as measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a novel imaging technique for noninvasive measurement of atherosclerotic inflammation. This was a cross-sectional study. Eighty-seven men without previously diagnosed cardiovascular disease or diabetes participated in the study. We measured the serum A-FABP, adiponectin, and leptin levels as well as other cardiovascular risk factors. Vascular inflammation in the carotid arterial wall, as indicated by the target to background ratio (TBR), was analyzed using FDG-PET. The circulating A-FABP and leptin levels had positive correlations with maximum TBR values (r = 0.38, P < 0.001; and r = 0.28, P = 0.010, respectively), whereas the adiponectin levels had a negative correlation (r = -0.31, P = 0.004). The maximum TBR levels exhibited an additive linear increment according to the rise in tertiles of the A-FABP levels in subjects with and without metabolic syndrome. Multiple regression analysis showed that serum A-FABP levels were independently associated with maximum TBR after adjustment for other cardiovascular risk factors (P = 0.006). Circulating A-FABP, adiponectin, and leptin levels were shown to be associated with vascular inflammation, as measured using FDG-PET. Specifically, the A-FABP level was an independent risk factor for vascular inflammation in Korean men without cardiovascular disease or diabetes.

Neuroepidemiology of epilepsy in northwest India.

Epilepsy has a complex etiology characterised by recurring seizures. To study clinical profile of epilepsy patients with reference to type of epilepsy in northwest India. No previous Indian study has reported relative incidence of various types of seizures with reference to type of epilepsy. Data of 400 epilepsy patients (200 idiopathic and 200 symptomatic) was collected for their clinical characteristics. The classification of epilepsy into idiopathic and symptomatic types was done on the basis of findings of EEG, CT scan and MRI tests. The age of onset of seizures was less than 15 years in only one third of the total patients. The number of non-vegetarians was higher in SE (68.5%) than IE (58%). The male to female ratio was significantly higher (1.33:1 in IE and 1.47:1 in SE). No difference was seen for place of residence (urban vs rural) patients with epilepsy (PWE). The majority of patients (58.5% of symptomatic and 52.8% idiopathic) though reported no triggering factors, yet many of them, when questioned, had held supernatural powers to be the cause of the disease. Sleep deprivation was reported as a major triggering factor by 28.5% of idiopathic epilepsy (IE) and 25% of symptomatic epilepsy (SE) patients. The incidence of mental retardation (1.25%) and behavioral disorders (7%) was found to be relatively low. Loss of memory was reported in 46% of IE and 43.5% of SE and poor scholastic performance in 23% of IE and 16.5% of SE. A positive history was recorded in 11% first-degree relatives and 4% second-degree relatives. Generalized seizures were more common in IE patients (67.5%), while partial seizures with and without secondary generalization (50.5%), and generalized seizures (49.5%) were equally common in SE. The study demonstrates differences in the type of seizures between idiopathic and symptomatic epilepsies and not other demographic, clinical and psycho-social traits. The males were found to have higher risk of epilepsy than females. The epidemiological characteristics of epileptics show variations across populations and also within population.

Centrifuge modelling of clay slope with montmorillonite weak layer under rainfall conditions

Rainfall is a major triggering factor for the failure of soil slopes, and weak layers, which can be commonly found within slopes, tend to act unfavourably upon slope stability. A series of centrifuge model tests was conducted to investigate the behaviour of clay slopes with highly permeable weak layers during rainfall. In addition, homogeneous slopes were also considered in the model tests as a comparison. The horizontal weak layers within the slopes were composed of a mixture of montmorillonite and filter paper scraps to obtain high permeability and compressibility due to saturation. Observations showed that the weak layers caused rainfall to infiltrate deeper in weak-layered slopes compared with the homogeneous slopes, which resulted in an additional displacement. On the other hand, the deformation of the weak layer itself also contributed to the additional displacement. Shear zones appeared in the slopes during rainfall, which became discontinuous at weak layers. The shear zones widened initially due to the development of deformation, but as rainfall persisted, they localized swiftly, leading to the failure of clay slopes.

Microbiological Findings and Treatment of EBV-Associated Hemophagocytic Lymphohistiocytosis: A Case Report

Epstein-Barr virus (EBV) is the major triggering factor for hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH). In patients with EBV-HLH, the EBV-infected T cells or natural killer cells are mostly mono- or oligoclonally proliferating, whereby hypercytokinemia plays a major role and causes hemophagocytosis, cellular damage, and dysfunction of various organs. This report describes the detection and treatment of EBV-associated HLH in the case of a 17-year-old male. Serum samples and skin swabs were tested for the presence of viral DNA using real-time PCR techniques. To confirm the molecular biological tests, electron microscopy was also performed. EBV DNA was detected with real-time PCR in both blood samples and skin swabs. The level of viral DNA constantly decreased during the applied therapy. The presence of the virus in the skin was confirmed by the appearance of herpes virus-like particles detected by electron microscopy in fluid taken from skin ulcerations. The results show that in terms of treatment, special therapeutic measures are required to control the cytokine storm generated by EBV and to suppress proliferating EBV genome-containing cells because the clinical course is often fulminate and results in a poor outcome. Therefore the potential of chemotherapy with a combination of steroids, etoposide, and cyclosporine to control HLH was assessed in the adolescent, who met the stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system.

Clinical Characteristics and Prognostic Factors of Stress-Induced Cardiomyopathy

Background and ObjectivesStress-induced cardiomyopathy (SCM) is characterized by a transient left ventricular (LV) dysfunction due to emotional and physical stress. There are limited data about the clinical characteristics in Korean patients. We sought to clarify the clinical features and prognosis in patients with SCM.Subjects and MethodsWe reviewed 39 cases diagnosed with SCM in a tertiary hospital. The SCM was diagnosed as: 1) no previous history of cardiac disease, 2) acute onset, 3) regional wall motion abnormality, typically in the takotsubo or inverted takotsubo shape by echocardiography, and 4) no significant stenosis in the coronary angiogram. We evaluated clinical characteristics, biomarkers, and prognosis.ResultsMean age was 61.3±16.1 years (female 69%). The triggering factors were physical stress in 32 patients (82%) and emotional stress in 5 patients (13%). The initial symptom was dyspnea (n=18, 46%) rather than chest pain (n=10, 26%). An initial electrocardiogram (EKG) presented T-wave inversion (n=18, 46%), ST-elevation (n=11, 28%), and ST-depression (n=2, 5%). Multivariate logistic regression analysis showed that initial high sensitive C-reactive protein (hs-CRP) {odds ratio (OR) 1.41, 95% confidence interval (CI); 1.02-1.97} and initial left ventricular ejection fraction (LVEF) (OR 0.89, 95% CI; 0.80-0.98) were significantly associated with death or cardiogenic shock, respectively.ConclusionThe major triggering factor of SCM is physical stress due to illness or surgical procedures, and the first manifestation is dyspnea rather than chest pain. Elevated hs-CRP and decreased LVEF at admission were independent risk factors for death or cardiogenic shock.

Hazard scenarios of truck drivers’ occupational accidents on and around trucks during loading and unloading

Recent epidemiological studies have shown that there is a clear need for efforts to prevent non-traffic occupational injuries among truck drivers. The objective of the present study was to establish the hazard scenarios for truck drivers during loading/unloading through analyses of text descriptions of accident processes. Focus was on accidents that were primarily related to movement/operation on and around the truck, which are particular to truck drivers. Special emphasis was placed on falls from heights, as this was shown to be the most frequent type of accident and a major cause of fractures among truck drivers. Analyses of text descriptions of 136 accidents, including 63 cases of fall from height, collected in one company over a period of three years, revealed that: (a) the major triggering factors for falls from heights on and around the truck were stepping off the edge at height (33.3%), wrong footing (27.0%), and loss of balance/control of wagon (15.9%); (b) the major triggering factors for accidents on and around the truck in general were slip/trip (44.1%) and defect/malfunction (14.7%). The present study identified four target areas for improving prevention of occupational accidents of truck drivers in connection with movement/operation on and around trucks during loading/unloading: (1) improvement of the procedures for unloading to reduce the risk of fall from the back-hatch lift, (2) improvements of shoes and housekeeping to reduce the risk of slip/trip, (3) improvement of truck maintenance, and (4) reconciliation of views on causes of accidents between employers and truck drivers as a first step for a dialogue for improving safety in the goods-transport branch.

Extensive genetic polymorphism in the haplotype STR-TNF and HLA class I with the onset and evolution of psoriasis vulgaris

Psoriasis is an inflammatory and autoimmune disease, clinically characterized by hyperproliferation of epidermis. The cause of the disease is unknown, but one of its most consistent associations involves the Major Histocompatibility Complex (MHC) and triggering factors [1]. Many genes are located in the MHC region and the most important is the tumor necrosis factor-alpha (TNF-α). Several polymorphisms, including microsatellites (Short Tandem Repeats – STR), were identified in the TNF-α gene found in the MHC class III region.

Hidradenitis suppurativa

Hidradenitis suppurativa is a chronic, recurrent, suppurative cutaneous disease. Despite its incidence, optimal medical or surgical treatment remains unclear. This review describes the disease, ranging from pathogenesis to treatment and prognosis. Articles were sourced from PubMed and Medline, using the MeSH terms 'hidradenitis suppurativa' and 'acne inversa'. Selection of articles was based on peer review, journal, relevance and English language. On the basis of histological findings, the disease is now considered inflammatory and originating from the hair follicle; therefore, the term 'acne inversa' is favoured by some experts. The exact aetiology remains obscure but smoking seems to be a major triggering factor. Treatment should be individualized according to the site and extent of the disease. Absolute cessation of smoking is essential in the treatment of hidradenitis. Management with antibiotics or other medications may relieve early symptoms, but radical surgery may be necessary for control and to prevent recurrence.