Stepwise Decline Research Articles

Return to Athletic Activity After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis

The cause of adolescent idiopathic scoliosis (AIS) is unknown and is currently believed to be multifactorial. AIS is a largely asymptomatic condition and many adolescents with AIS are involved with organized athletics and physical activity. To date, no data exist indicating predictors of return to physical activity after posterior spinal fusion for AIS. In this cohort study, adolescents who underwent posterior spinal fusion for AIS were evaluated to determine what clinical, surgical, and demographic variables predicted rate of return play in organized athletics. Forty-two athletically active adolescents who underwent posterior spinal fusion for AIS at a single tertiary care academic orthopaedic institution by a single surgeon were analyzed for clinical, surgical, and demographic predictors of return to presurgical activity levels. Data were collected by chart review, patient interview, and completion of postoperative SRS-22 outcomes score. At an average of 5.5 years follow-up, 25 patients (59.5%) had returned to sports at an equal or higher level of physical activity. Three variables were independently associated with return to athletic activity postoperatively. The relationship between distal level of fusion and rate of return to play demonstrated a statistically significant stepwise decline from T11 to L4. Lenke classification and final SRS-22 score were also predictive of return to activity. No complications related to return to play were reported. In this retrospective cohort study, distal level of fusion, Lenke classification, and postoperative SRS-22 score were each independent predictors of rate of return to preoperative level of athletic activity after posterior spinal fusion for AIS. Prognostic Level II: retrospective Study.

Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

Hospice eligibility in patients who died in a tertiary care center

Hospice is a service that patients, families, and physicians find beneficial, yet a majority of patients die without receiving hospice care. Little is known about how many hospitalized patients are hospice eligible at the time of hospitalization. Retrospective chart review was used to examine all adult deaths (n = 688) at a tertiary care center during 2009. Charts were selected for full review if the death was nontraumatic and the patient had a hospital admission within 12 months of the terminal admission. The charts were examined for hospice eligibility based on medical criteria, evidence of a hospice discussion, and hospice enrollment. Two hundred nine patients had an admission in the year preceding the terminal admission and a nontraumatic death. Sixty percent were hospice eligible during the penultimate admission. Hospice discussions were documented in 14% of the hospice-eligible patients. Patients who were hospice eligible had more subspecialty consults on the penultimate admission compared to those not hospice eligible (P = 0.016), as well as more overall hospitalizations in the 12 months preceding their terminal admission (P = 0.0003), and fewer days between their penultimate admission and death (P = 0.001). The majority of terminally ill inpatients did not have a documented discussion of hospice with their care provider. Educating physicians to recognize the stepwise decline of most illnesses and hospice admission criteria will facilitate a more informed decision-making process for patients and their families. A consistent commitment to offer hospice earlier than the terminal admission would increase access to community or home-based care, potentially increasing quality of life.

Are we ready? Preparedness of acute care providers for the Rugby World Cup 2011 in New Zealand

New Zealand is hosting the Rugby World Cup (RWC) 2011. It is the largest sporting event in New Zealand's history, with around 70 000 fans estimated to visit the country...

Circulating Angiopoietic Cells and Diabetic Retinopathy in Type 2 Diabetes Mellitus, with or without Macrovascular Disease

To investigate different types of circulating angiopoietic cells, such as vasculogenic circulating progenitor cells (CPCs), endothelial progenitor cells (EPCs), and mature EPCs (matEPCs) in patients with type 2 diabetes mellitus (T2DM), with or without diabetic retinopathy (DR) and with or without macrovascular disease (MVD). One hundred twenty-six patients with T2DM-66 with MVD and 60 without MVD-were enrolled in a case-control study. MVD comprised coronary heart disease, peripheral arterial disease, stroke, or various combinations of those conditions. By a modified Early Treatment of Diabetic Retinopathy Study (ETDRS) classification, 55 patients were classified without DR (CO), 19 with mild nonproliferative DR (mNPDR), 16 with moderate-severe NPDR (msNPDR), 19 with early proliferative diabetic retinopathy (ePDR), and 17 with high-risk PDR (hrPDR). CPCs (CD34/CD133), EPCs (CD34/CD133/CD30), and matEPCs (CD34/CD133/CD309/CD31) were enumerated by flow cytometry. Patients with MVD CPCs, EPCs, and matEPCs showed a significant, stepwise decline with advancing stages of retinopathy. In contrast, in the patients without MVD, EPCs and matEPCs reached up to 56% of CPCs and 37% of EPCs. On the other hand, the percentage of EPCs and matEPCs was reduced to 5% of CPCs and EPCs each in MVD patients. Thus, the percentage of EPCs and matEPCs in comparison with that of CPCs and EPCs represented an 11- and 7-fold difference. The circulating angiopoietic CPCs, EPCs, and matEPCs in T2DM patients with DR had a different regulations, with increasing relative differences occurring in proliferative DR, apparently depending on the macrovascular comorbidities. Patients with MVD showed a strong retinopathy-stage-dependent depletion of all angiopoietic cells.

Medical Students’ Attitudes to Professionalism: An Opportunity for the GP Tutor?

Using a novel tool based on General Medical Council (GMC) standards, this cross-sectional survey aimed to assess UK medical students' professional attitudes at different stages of the curriculum, and to investigate the influence of the hidden curriculum on these attitudes through exposure to unprofessional behaviour during the medical course. An anonymous online questionnaire was developed, reflecting core professional competences outlined in Good Medical Practice. First, third and fifth year students received Section 1: 'Attitudes to professionalism'; third and fifth year students also received Section 2: 'Exposure to unprofessional behaviour'. 'Professionalism score' (Section 1) and 'Exposure score' (Section 2) were analysed using ANOVA. Thematic analysis was used to analyse free text. Response rate was 50.8% (363/714). Female (F=18.24, p < 0.001) and first year students (F=12.22, p < 0.001) had significantly higher Professionalism scores. Professionalism scores for male students showed a significant stepwise decline from first year to fifth year. Fifth year students had significantly higher Exposure scores (F=23.4, p < 0.001). Qualitative themes included bullying, lack of accountability and sexism. Sensitivity to professionalism, as defined by the GMC, was higher and exposure to unprofessional behaviour lower in first year compared to fifth year. Addressing the hidden curriculum is crucial to protect professional development; GP teachers should be aware of these findings and are ideally placed to provide mentorship and support to medical students.

Isotopic evidence for an anomalously low oceanic sulfate concentration following end-Permian mass extinction

The cataclysmic end-Permian mass extinction was immediately followed by a global expansion of microbial ecosystems, as demonstrated by widespread microbialite sequences (disaster facies) in shallow water settings. Here we present high-resolution carbonate carbon ( δ 13C carb) and carbonate-associated sulfate–sulfur isotope ( δ 34S CAS) records from the microbialite in the Cili Permian–Triassic (P–Tr) section in South China. A stepwise decline in δ 13C carb begins in the underlying skeletal limestone, predating the main oceanic mass extinction and the first appearance of microbialite, and reaches its nadir in the upper part of the microbialite layer. The corresponding δ 34S CAS, in the range of 17.4‰ to 27.4‰, is relatively stable in the underlying skeletal limestone, and increases gradually from 2 m below the microbialite rising to a peak at the base of the microbialite. Two episodes of positive and negative shifts occurred within the microbialite layer, and exhibit a remarkable co-variance of sulfur and carbon isotope composition. The large amplitude of the variation in δ 34S CAS, as high as 7‰ per 100 kiloyears, suggests a small oceanic sulfate reservoir size at this time. Furthermore, the δ 13C carb and δ 34S CAS records co-vary without phase lag throughout the microbialite interval, implying a marine-driven C cycle in an anoxic ocean with anomalously low oceanic sulfate concentrations. On the basis of a non-steady-state box model, we argue that the oceanic sulfate concentration may have fallen to less than 15%, perhaps as low as 3%, of that in the modern oceans. Low oceanic sulfate concentration likely was the consequence of evaporite deposition and widespread anoxic/sulfidic conditions prior to the main mass extinction. By promoting methanogenesis and a build-up of atmospheric CH 4 and CO 2, low oceanic sulfate may have intensified global warming, exacerbating the inimical environmental conditions of the latest Permian.

Surgical approaches to brainstem cavernous malformations

Brainstem cavernous malformations (CMs) are low-flow vascular lesions in eloquent locations. Their presentation is often marked with symptomatic hemorrhages that appear to occur more frequently than hemorrhage from supratentorial cavernomas. Brainstem CMs can be removed using 1 of the 5 standard skull-base approaches: retrosigmoid, suboccipital (with or without telovelar approach), supracerebellar infratentorial, orbitozygomatic, and far lateral. Patients being referred to a tertiary institution often have lesions that are aggressive with respect to bleeding rates. Nonetheless, the indications for surgery, in the authors' opinion, are the same for all lesions: those that are symptomatic, those that cause mass effect, or those that abut a pial surface. Patients often have relapsing and remitting courses of symptoms, with each hemorrhage causing a progressive and stepwise decline. Many patients experience new postoperative deficits, most of which are transient and resolve fully. Despite the risks associated with operating in this highly eloquent tissue, most patients have had favorable outcomes in the authors' experience. Surgical treatment of brainstem CMs protects patients from the potentially devastating effects of rehemorrhage, and the authors believe that the benefits of intervention outweigh the risks in patients with the appropriate indications.

Assessment of bile salt effects on s-layer production, slp gene expression and some physicochemical properties of Lactobacillus acidophilus ATCC 4356.

In many conditions, bacterial surface properties are changed as a result of variation in growth medium and conditions. This study examined the influence of bile salt concentrations (0-0.1%) on colony morphotype, hydrophobicity, H2O2 concentration, S-layer protein production and slpA gene expression in Lactobacillus acidophilus ATCC 4356. It was observed that two types of colonies (R and S) were in the control group and the stress condition. When the bile level increased in the medium, the amount of S type was more than the R. A stepwise increment in the bile concentration resulted in a stepwise decline in the maximum growth rate. The results showed that hydrophobicity was increased in 0.01%-0.02% bile but it was decreased in 0.1% bile. Treatment by bile (0.01%- 0.1%) profoundly decreased H2O2 formation. S-layer protein and slpA gene expression was also altered by stress condition. S-protein expression was increased in stress condition. slpA gene expression increased in 0.01%-0.05% bile and it decreased in 0.1% bile. However, we found that different of bile salt concentrations influence on morphology and some surface properties of L. acidophilus ATCC 4356. These changes were very different in the 0.1% bile. It appears that the bacteria respond abruptly to 0.1% bile.

The natural history of cervical spondylotic myelopathy

The objective of this systematic review was to use evidence-based medicine to delineate the natural history of cervical spondylotic myelopathy (CSM) and identify factors associated with clinical deterioration. The National Library of Medicine and Cochrane Database were queried using MeSH headings and keywords relevant to the natural history of CSM. Abstracts were reviewed and studies meeting the inclusion criteria were selected. The guidelines group assembled an evidentiary table summarizing the quality of evidence (Classes I-III). Disagreements regarding the level of evidence were resolved through an expert consensus conference. The group formulated recommendations that contained the degree of strength based on the Scottish Intercollegiate Guidelines network. Validation was done through peer review by the Joint Guidelines Committee of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. The natural history of CSM is mixed: it may manifest as a slow, stepwise decline or there may be a long period of quiescence (Class III). Long periods of severe stenosis are associated with demyelination and may result in necrosis of both gray and white matter. With severe and/or long lasting CSM symptoms, the likelihood of improvement with nonoperative measures is low. Objectively measurable deterioration is rarely seen acutely in patients younger than 75 years of age with mild CSM (modified Japanese Orthopaedic Association scale score > 12; Class I). In patients with cervical stenosis without myelopathy, the presence of abnormal electromyography findings or the presence of clinical radiculopathy is associated with the development of symptomatic CSM in this patient population (Class I). The natural history of CSM is variable, which may affect treatment decisions.

Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging

To evaluate the relationship between coronary artery calcium (CAC) and coronary vasodilator function. We evaluated 136 patients without known coronary artery disease (CAD) undergoing vasodilator stress (82)Rb PET/CT and CAC scoring who showed normal myocardial perfusion. The CAC score, resting and hyperemic myocardial blood flow (MBF), coronary flow reserve (CFR) and coronary vascular resistance were analyzed. Global and regional CAC scores showed significant but weak inverse correlations with hyperemic MBF (r=-0.31 and r=-0.26, p< or =0.0002 respectively) and CFR (r=-0.28 and r=-0.2, p< or =0.001 respectively). With increasing CAC score, there was a modest stepwise decline in CFR on a per-patient basis (1.8+/-0.5 vs 1.7+/-0.5 vs 1.5+/-0.4, p=0.048, with total CAC=0, 1-400 and >400, respectively) and on a per-vessel basis. In multivariable modeling only body mass index and CAC score were predictive of CFR. In patients with an intermediate likelihood of, but without overt, CAD, there is a statistically significant but weak inverse correlation between CAC content and coronary vasodilator function. The strength of this association weakens after adjusting CAC scores for age, gender and coronary risk factors. This suggests that CAC and coronary vasodilator function provide biologically different information regarding atherosclerosis.

Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis†

Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well-documented morphological abnormality seen on transmission electron microscopy in this disease. It has been suggested that IMCs consist of phospholipids, but their exact composition remain uncertain many years after their discovery. Micellar phase transitions of phospholipid bilayers is a well-known but little-studied phenomenon in living systems. Its presence in the mitochondria of NASH would offer significant insight into the disease with possible therapeutic implications. We postulated that intramitochondrial disturbances in NASH are sufficient to produce such transitions and that their detection in fresh biopsies would therefore be a dynamic process. To test this, we performed a blinded, prospective analysis of fresh liver biopsy samples immediately fixed under different conditions. Quantitative transmission electron microscopy morphometry, performed by systematically counting total mitochondria and IMCs within areas of uniform dimension, showed a stepwise decline in IMCs with cooler fixation temperature in each subject studied. Randomization testing (Monte Carlo resampling) confirmed that the detection of IMCs was strongly dependent on fixation temperature (P < 0.0001). These results indicate that the intramitochondrial crystals characteristic of NASH are highly dynamic and unstable structures. The findings offer the strongest support yet for their origin in micellar phase transitions. We speculate that such transitions result from microenvironmental changes within the mitochondria and carry therapeutic implications, especially in regard to dietary manipulations of mitochondrial lipid composition.

Effects of Illegal Harvest of Eggs on the Population Decline of Leatherback Turtles in Las Baulas Marine National Park, Costa Rica

Within 19 years the nesting population of leatherback turtles (Dermochelys coriacea) at Parque Nacional Marino Las Baulas declined from 1500 turtles nesting per year to about 100. We analyzed the effects of fishery bycatch and illegal harvesting (poaching) of eggs on this population. We modeled the population response to different levels of egg harvest (90, 75, 50, and 25%) and the effect of eradicating poaching at different times during the population decline. We compared effects of 90% poaching with those of 20% adult mortality because both of these processes were present in the population at Las Baulas. There was a stepwise decline in number of nesting turtles at all levels of egg harvest. Extirpation times for different levels of poaching ranged from 45 to 282 years. The nesting population declined more slowly and survived longer with 20% adult mortality (146 years) than it did with 90% poaching (45 years). Time that elapsed until poaching stopped determined the average population size at which the population stabilized, ranging from 90 to 420 nesting turtles. Our model predicted that saving clutches lost naturally would restore the population when adult mortality rates were low and would contribute more to population recovery when there were short remigration intervals between nesting seasons and a large proportion of natural loss of clutches. Because the model indicated that poaching was the most important cause of the leatherback decline at Las Baulas, protecting nests on the beach and protecting the beach from development are critical for survival of this population. Nevertheless, the model predicted that current high mortality rates of adults will prevent population recovery. Therefore, protection of the beach habitat and nests must be continued and fishery bycatch must be reduced to save this population.

Expanding use of emergency endovascular repair for ruptured abdominal aortic aneurysms: Disparities in outcomes from a nationwide perspective

Endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) has become widely accepted in the elective setting but remains controversial for emergency repair of ruptured aneurysms (rAAA). We sought to examine the national trends in use and associated outcomes with EVAR. The Nationwide Inpatient Sample (NIS) was used to analyze all admissions for rAAA from 2001 through 2004. Nationwide temporal trends and demographics using weighted samples were evaluated. Focused univariate and multivariate analyses comparing outcomes from open repair and EVAR were done for the years 2003 and 2004. There were 28,123 admissions for rAAA, with a stepwise decline in admissions from 2001 to 2004. Use of EVAR increased significantly from 6% of all emergency repairs in 2001 to 11% in 2004 (P < .01). Mortality for EVAR declined significantly from 43% to 29% (P < .01), but mortality with open repair showed no change (40% to 43%). From the 2003 to 2004 data set, 949 EVAR and 8982 open repairs were identified. Compared with open repair, the EVAR patients had lower mortality (31% vs 42%), shorter hospital stay (6 vs 9 days), and were more likely to be discharged to home (59% vs 37%, all P < .01). The total hospital charges for EVAR and open repair were similar (dollars 71,428 vs $74,520, P = .59). Mortality for EVAR was significantly higher at nonteaching hospitals compared with teaching centers (55% vs 21%, P < .01) and at nonteaching centers, even exceeding that of open repair (46%). Regression modeling confirmed the overall benefits of EVAR as well as the worse outcomes at nonteaching facilities after adjusting for patient comorbidities, disease severity, and hospital or system covariates. Endovascular repair is being increasingly used in the emergency management of ruptured AAA, with steadily decreasing mortality during the study period. Endovascular AAA repair is associated with improved mortality and outcomes compared with open repair, but results in nonteaching centers are substantially worse than those in teaching hospitals.

Stepwise Decline in Visual Field After Serial Sildenafil Use

Stepwise Decline in Visual Field After Serial Sildenafil Use

Ucma, a Novel Secreted Cartilage-specific Protein with Implications in Osteogenesis

Here we report on the structure, expression, and function of a novel cartilage-specific gene coding for a 17-kDa small, highly charged, and secreted protein that we termed Ucma (unique cartilage matrix-associated protein). The protein is processed by a furin-like protease into an N-terminal peptide of 37 amino acids and a C-terminal fragment (Ucma-C) of 74 amino acids. Ucma is highly conserved between mouse, rat, human, dog, clawed frog, and zebrafish, but has no homology to other known proteins. Remarkable are 1-2 tyrosine sulfate residues/molecule and dense clusters of acidic and basic residues in the C-terminal part. In the developing mouse skeleton Ucma mRNA is expressed in resting chondrocytes in the distal and peripheral zones of epiphyseal and vertebral cartilage. Ucma is secreted into the extracellular matrix as an uncleaved precursor and shows the same restricted distribution pattern in cartilage as Ucma mRNA. In contrast, antibodies prepared against the processed C-terminal fragment located Ucma-C in the entire cartilage matrix, indicating that it either diffuses or is retained until chondrocytes reach hypertrophy. During differentiation of an MC615 chondrocyte subclone in vitro, Ucma expression parallels largely the expression of collagen II and decreases with maturation toward hypertrophic cells. Recombinant Ucma-C does not affect expression of chondrocyte-specific genes or proliferation of chondrocytes, but interferes with osteogenic differentiation of primary osteoblasts, mesenchymal stem cells, and MC3T3-E1 pre-osteoblasts. These findings suggest that Ucma may be involved in the negative control of osteogenic differentiation of osteochondrogenic precursor cells in peripheral zones of fetal cartilage and at the cartilage-bone interface.

Semantic Clustering Inefficiency in HIV-Associated Dementia

Although HIV is detectable throughout the CNS, its preferential disruption of fronto-basal ganglia systems is thought to underlie the neurobehavioral syndrome of HIV-associated dementia. Semantic clustering, a measure of organizational strategy during learning and retrieval, is commonly impaired in patients with frontal systems dysfunction, but has not previously been evaluated in HIV-associated dementia. The current study examined semantic and serial clustering strategies on a list-learning task in 15 individuals with HIV-associated dementia, 44 HIV-infected individuals without dementia, and 24 healthy comparison subjects. Results indicated a stepwise decline in the use of semantic, but not serial, clustering with increasing severity of HIV-associated cognitive disorder. Findings suggest that HIV-associated dementia is associated with inefficient use of higher-level encoding and retrieval strategies, perhaps mediated by a disruption of fronto-basal ganglia systems.

The effect of hypoxia on behavioural and physiological aspects of lesser sandeel, Ammodytes tobianus (Linnaeus, 1785)

Lesser sandeel (Ammodytes tobianus) is abundant in near-shore areas where it is a key prey. It exhibits the behaviour of alternating between swimming in schools and lying buried in the sediment. We first determined the species’ standard metabolic rate (SMR), critical partial pressure of oxygen \((P_{{\rm O}_{2{\rm crit}}})\) and maximal oxygen uptake \((M_{{\rm O}_{2{\rm max}}}).\) The sandeel were then exposed to an acute stepwise decline in water oxygen pressure (18.4, 13.8, 9.8, 7.5, 5.8, 4.0, and 3.1 kPa \(P_{{\rm O}_{2}}\)). Swimming speed and routine- and post-experimental blood lactate levels were measured, in addition to levels associated with strenuous exercise. The SMR was 69.0 ± 8.4 mg O2 kg−1 h−1 and the \(M_{{\rm O}_{2{\rm max}}}\) about seven times as high. The \(P_{{\rm O}_{2{\rm crit}}}\) was found to be 4.1 kPa. A rapid decrease (within 1 h) in \(P_{{\rm O}_{2}}\) from 18.4 to 3.1 kPa had no significant effect on routine swimming speed (0.9 ± 0.06 bl s−1), but steady levels at the lowest \(P_{{\rm O}_{2}}\) (3.1 kPa) gradually reduced the swimming speed by 95% after 40 min. The routine blood lactate levels were 2.2 ± 0.6 mmol l−1, while the levels in the strenuously exercised groups were significantly higher with 5.4 ± 1.6 and 5.8 ± 1.3 mmol l−1. The highest levels were observed in post-experimental fish with 7.5 ± 2.7 mmol l−1. We argue that, as sandeel showed no decrease in swimming speed (to offset stress) nor an increased speed to escape the hypoxia, the fish either rely on a low SMR and being a reasonable strong oxygen regulator \((\hbox{low}\;P_{{\rm O}_{2{\rm crit}}})\) as a mean to cope when exposed to acute hypoxia, or that the hypoxia simply developed too fast for the fish to decide on an appropriate strategy. Not showing a behavioural response may in the present case be maladaptive, as the consequence was major physiological stress which the fish however appears tolerant towards. The high routine blood lactate levels suggest that anaerobic metabolism is associated with swimming in sandeel, which may be related to the specific lifestyle of the fish where they regularly bury in the sediment.

Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline

Background: The anterior-medial thalamus (AMT), which is associated with memory processing, is severely affected by Alzheimer’s disease pathology and, when damaged, can be the sole cause of dementia. Objective: To...

The Terrorist Attacks of September 11, 2001, as Psychological Toxin

Previous studies of psychological morbidity produced by September 11, 2001, focused primarily on short-term development of posttraumatic stress disorder or depression in East Coast cities targeted. This study aimed to determine whether suicide attempts medically harmful enough to necessitate admission to the general hospital increased in the 2 years following September 11, 2001, in a region not on the East Coast, and if so, to characterize individuals contributing to this increase. This retrospective study compared two time periods: 2 years preceding and 2 years following September 11, 2001. Psychiatric consultation reports for all suicide attempters medically admitted to the University of Michigan Health Systems Hospital in Ann Arbor, Michigan, were examined (N = 254). In the 2-year period following September 11, 2001, there was a 49% increase in the number of individuals making a harmful suicide attempt (p = 0.002). The effect was greatest in the months following the attacks but continued over the next year, with a stepwise decline corresponding to the number of months elapsed since September 11. In the period following September 11, 2001, fewer subjects reported multiple personal stressors (p = 0.03). The subjects in the two time periods were not significantly different in age, gender, prior suicide attempts, prior psychiatric treatment, alcohol abuse, substance abuse, depression, or psychosis. Overrepresentation by those most vulnerable to suicide attempts did not account for the increased number of suicide attempts. The effects of chronic stress in the general population across the United States elicited by the terrorism of September 11, 2001, may have been of greater magnitude and longer lasting than previously realized.