A 15-year Medicaid data set (1996-2010) from one state was analyz

A 15-year Medicaid data set (1996-2010) from one state was analyzed. The selection criteria specified patients 17 years of age or younger with a diagnosis of ASD primum, secundum, or sinus venosus on one or more service visits to a pediatrician or pediatric cardiologist. During the 15-year period, ASDs represented a prevalence rate for treatment

of 0.47/1000 CHDs identified, with 61 % presenting as complex lesions. Concomitant cardiac anomalies that might have a negative impact on prognosis were present including patent ductus arteriosus (26.1 %), pulmonary hypertension (3.8 %), and supraventricular tachycardia (2.4 %). Pharmacologic treatments, predominantly diuretics, were prescribed for 21 % of the cohort. Both surgical closures (6.3 %) and transcatheter closures (1.4 %) were used for ASD secundum cases, whereas surgical closures predominated for ASD primum (25.6 %) and sinus venosus selleck products (13.5 %) lesions. The postoperative follow-up period was two to three times longer for children with ASD primum or sinus venosus than for those with ASD secundum (average, similar to 1 year). Factors predicting the likelihood of having

ASD closure were older age, having a concomitant patent ductus arteriosus (PDA) repair, treatment with ibuprofen, having two or more concomitant CHDs, and receiving diuretics or preload/afterload-reducing agents. Care of ASDs in routine practice settings involves more complications and appears to be more conservative than portrayed in previous investigations of isolated ASDs.”
“Cyanobacteria are prevalent in the freshwater environment, selleck reaching critical mass in harmful algal blooms. These organisms produce a variety of toxins including endotoxins such as lipopolysaccharides LY2090314 research buy (LPS), which have been previously

shown to decrease glutathione-S-transferase (GST) activity in zebrafish (Danio rerio) embryos. GST plays a vital role in detoxification response during oxidative stress and provides a first line of defense after toxic heavy metal insult, before increased metallothionein expression. Although some attention has focused on cyanobacterial LPS, little research has focused on effects of concurrent exposures with other toxicants. Because cyanobacterial LPS can alter detoxification enzymes including GST, we hypothesized that cyanobacterial LPS could potentiate metal toxicity. This study investigated the effects of LPS from two cyanobacterial species, Lyngbya spp. and Microcystis aeruginosa, on cadmium toxicity in zebrafish embryos. Forty-eight-hour CdCl(2) LC(50) values showed that coexposure of cadmium and Lyngbya LPS or Microcystis LPS resulted in significantly increased cadmium toxicity in comparison with cadmium alone. However, increased cadmium toxicity was not due to decreased GST activity as initially hypothesized.

Indeed, recombination was often favoured even though the linkage

Indeed, recombination was often favoured even though the linkage disequilibrium remained of constant sign throughout the simulations. We conclude that Red Queen-type dynamics involving persistent fluctuations in host and parasite AZD6738 genotype frequencies appear to not be an artefact of specific assumptions about host-parasite fitness interactions, but emerge readily with the general interactions studied here. Our results also indicate that although recombination is often favoured, some of the factors previously thought to be important in this process such as linkage disequilibrium fluctuations

need to be reassessed when fitness interactions between hosts and parasites are complex.”

mobility degradation has been studied in high-dose-boron-implanted ultrashallow junctions containing high concentrations of boron-interstitial clusters (BICs), combining an empirical method based on the self-consistent interpretation of secondary-ion-mass spectrometry (SIMS) and Hall measurements and liquid-nitrogen (LN(2)) to room temperature (RT) hole mobility measurements. It has been found that BICs act as independent scattering centers which have a strong impact on hole mobility in addition to the other scattering mechanisms such as lattice and impurities scattering. Lapatinib in vivo A mobility degradation coefficient alpha has been introduced, which gives information on the mobility degradation level in the analyzed junctions. In the case Tubastatin A of very high concentrations of BICs (containing a boron density up to 8 x 10(14) cm(-2)), measured hole mobilities were found to be similar to 40% lower than corresponding theoretical values. BICs dissolution through multiple Flash anneals at high temperature (1300 degrees C) reduces the observe mobility degradation. (C) 2010 American Institute of Physics. [doi:10.1063/1.3446844]“
“Purpose: The process of breast cancer follow-up has psychosocial benefits for patients,

notably reassurance, although attending hospital appointments can increase anxiety. Discharge from hospital followup can also invoke anxiety as many patients seek reassurance from continued specialist follow-up. Inevitably, due to increased survival and associated resource issues, opportunities for follow-up and support will be reduced. We delivered and evaluated an intervention which supported the transition from cancer patient to cancer survivor, for breast cancer patients being discharged to primary care.

Methods: We delivered and evaluated a pilot of a patient-centred group intervention ‘Preparing Patients for Discharge’, aimed at reducing distress.

4% and 49 9% in the

sagittal 3-dimensional computed tomog

4% and 49.9% in the

sagittal 3-dimensional computed tomography SYN-117 datasheet plane, respectively. And, subsidences of titanium cages at upper and lower segment endplates were 1.26 mm and 0.72 mm in the coronal plane and 1.04 mm and 0.53 mm in the sagittal plane, respectively.

Conclusion. The ratio of fused area of local bone inside cages at regions exposed to endplates was <50%, which is insufficient for physiologic load transmission. The authors recommend that additional bone should be grafted into the disc space or new bone bonding inter-body spacer should be considered.”
“Switching between bioequivalent antiepileptic drugs (AEDs) in patients with epilepsy remains a concern because of possible untoward effects owing to a narrow therapeutic range, We investigated the association between switching A-rated AEDs and epilepsy-related events. We conducted a case-control study buy BYL719 using claims from the MarketScan database. Cases were defined by an emergently treated epilepsy-related event with the primary diagnosis of epilepsy. Controls had air epilepsy Outpatient office visit. Eighty-four of 757 (11.1%) cases and 147 of 2271 (6.5%) controls experienced

an A-rated switch. The odds of air epilepsy-related event were 1.78-fold higher for switchers; (95% CI 1.35 to 2.36) and, when adjusted for gender and total number of AED prescriptions filled, 1.57-fold higher (95% CI = 1.17-2.10). Switching between A-rated formulations of AEDs is associated with an increased risk of emergently treated epilepsy-related events. These findings suggest that care should be taken when considering a switch between A-rated AEDs in patients with epilepsy. (C) 2009 Elsevier Inc. All rights reserved.”
“The present study aimed to clarify the relationship between sugars and vitamin C in fruit. The objective was to determine whether vitamin C content was regulated by sugar Crenolanib clinical trial content due to the role of sugar as a precursor for vitamin C. During summer, maximal content in sugar and vitamin C were found in both genotypes

tested Solanum lycopersicon ‘Cervil’ and ‘Levovil’. During autumn, fruit pruning increased fruit size and hexose content but fruit vitamin C content did not increase. Therefore sugar substrate was not limiting for vitamin C synthesis during autumn. We demonstrated for two cultivars, ‘Cervil’ and ‘Levovil’, with different sugar accumulation profiles during ripening, that sugar content was not determinant in the regulation of vitamin C content. The strong correlation observed between sugars and vitamin C in ‘Cervil’ was due to their concomitant increase during fruit ripening. (C) 2010 Elsevier Masson SAS. All rights reserved.”
“The purpose of this study was to determine reproducibility, validity, and responsiveness of the Work Limitations Questionnaire (WLQ) among cancer survivors.

A cohort of 53 cancer survivors completed the WLQ and other questionnaires at baseline, 4-week, and 6-month follow-up.

Shoulder, scapula, trunk list, pelvis, scoliosis, and waist angle

Shoulder, scapula, trunk list, pelvis, scoliosis, and waist angles indices were calculated with specially designed software. Frontal and sagittal Cobb angles and trunk list were also calculated on radiographs. The Pearson correlation coefficients (r) was used to estimate concurrent validity of the 2D clinical postural tool of the trunk with indices extracted from the 3D system BMS-754807 research buy and with those obtained from radiographs.

Results. The correlation between 2D and 3D indices was good to excellent for shoulder, pelvis, trunk list, and thoracic scoliosis (0.81 > r < 0.97; P < 0.01) but fair to moderate for thoracic kyphosis, lumbar lordosis, and thoracolumbar or lumbar scoliosis (0.30 >

r < 0.56; P < 0.05). The correlation between 2D and radiograph

spinal indices was fair to good (-0.33 to -0.80 with Cobb angles and 0.76 for trunk list; P < 0.05).

Conclusion. This tool will facilitate clinical practice by monitoring trunk posture among persons with IS. Further, it may contribute to a reduction in the use of radiographs to monitor scoliosis progression.”
“The sulfonyl epoxy monomer (SEP) was synthesized and further to blend with the diglycidyl ether of bisphenol A (DGEBA). The glass transition temperature (T(g)) of the SEP/DGEBA blended materials increased from 103.7 to 163.8 degrees C. The cross-linking density and polymer chain self-association intra-molecular SIS3 chemical structure action affected more than that the polymer-polymer intermolecular action (hydrogen bonding) in the SEP blended with the DGEBA materials. The excess stabilization energy in the overall stabilization was only 0.00145% (14.5 ppm), which indicated that the polymer-polymer intermolecular action was weak. The thermal degradation of the SEP segments could form various sulfate derivatives at lower temperature and analyzed by the TGA/GC/Mass. The sulfate derivatives could generate the thermal stable chars, which provided the “”shielding effect”" and antioxidation property. Additionally, Tipifarnib in vitro these chars could also improve the protective effect and inhibit the thermal-oxidation decomposition under the

air atmosphere. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 118: 2165-2175, 2010″
“We addressed the effect of post-transplant lymphoproliferative disorder (PTLD) treatment with rituximab monotherapy or CHOP-based chemotherapy (+/- rituximab) after upfront immunosuppression reduction (IR) on renal graft function in a longitudinal analysis of 58 renal transplant recipients with PTLD and 610 renal transplant controls. Changes in the estimated glomerular filtration rate over time were calculated from a total of 6933 creatinine measurements over a period of > 1 year using a linear mixed model with random and fixed effects. Renal graft function significantly improved with treatment of PTLD, especially in the chemotherapy subgroup.

“Herein, we report the isolation and immunomodulatory acti

“Herein, we report the isolation and immunomodulatory activity of 11 phytoconstituents, viz. 7 flavonoids, 3 pentacyclic triterpenes and 1 phytosterol of an unexplored plant Actinocarya tibetica Benth. Three flavones, 5-methoxy-6,7-methylenedioxyflavone Selleck Batimastat (6), mosloflavone (7) and negletein (8), showed promising anti-inflammatory activity via inhibition of TNF-alpha and IL-1 with IC50 values of 0.22, 0.71, 16.4M and 10.8, 7.8, 6.4M, respectively. These flavones

also showed dose-dependent inhibition of TNF-alpha, IL-1 and iNOS levels in the supernatant of mouse macrophage cell line J774A. Molecular modelling studies revealed orientation and interactions of flavones 6-8 in the active site of TNF-alpha. These flavones can be used as a starting point to discover lead structures for treatment of inflammatory and immunomodulatory diseases.”
“Through comparison between the oxygen precipitation (OP) behaviors in heavily and lightly phosphorus (P)-doped Czochralski silicon (CZ-Si) crystals subjected to low-high two-step anneal of 600, 650, or 750 degrees C/8 h+ 1050 degrees C/16 h, we have found that in heavily P-doped CZ-Si, OP is much stronger in the case with the

nucleation anneal at 600 or 650 degrees C while it is to some extent suppressed in the case with the nucleation anneal at 750 degrees C in contrast to lightly doped CZ-Si where nucleation is enhanced at 750 degrees C. Transmission electron microscopy investigation reveals that silicon phosphide precipitates of face-centered-cubic www.selleckchem.com/products/H-89-dihydrochloride.html AZD8055 clinical trial SiP form during the nucleation anneal at temperatures 650 degrees C and below. The SiP precipitates act as the heterogeneous nuclei for OP during the subsequent high temperature anneal while the oxygen precipitate nuclei containing certain amounts of P atoms generate during the nucleation anneal at 750 degrees C. They are further coarsened to be larger oxygen precipitates during the subsequent high temperature

anneal. Of significance is that the oxygen precipitate nucleation mechanism operating at certain temperatures for heavily P-doped CZ-Si is found to be completely different from that of lightly P-doped CZ-Si. We believe that the present work provides a further insight into OP in CZ-Si. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3120943]“
“Background: Acute myeloid leukemia (AML), whether de novo or arising from antecedent hematologic disorders in elderly patients, is less likely to be curable with standard chemotherapy regimens used for younger patients. Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the most efficient anti-leukemia treatment for AML and has shown a survival advantage in younger patients with intermediate-or poor-risk cytogenetics.

Methods: The authors review their experience as well as the published data regarding the role of reduced-intensity conditioning (RIC) allo-HCT in adults with AML.

In the present study, we aimed to analyze the cancer stem cell po

In the present study, we aimed to analyze the cancer stem cell population in MUC4 overexpressed ovarian cancer cells.


MUC4 was ectopically overexpressed in SKOV3 ovarian cancer cells. Western blot analysis was performed for MUC4, HER2, CD133, ALDH1 and Shh expression in MUC4 overexpressed cells. Confocal analysis of MUC4, HER2 and CD133 was also done in the MUC4 overexpressed cells. CD133 and Hoechst33342 check details dye staining was used to analyze the cancer stem cell population via FACS method in SKOV3-MUC4 cells.

Results: MUC4 overexpressed SKOV3 cells showed an increased expression of HER2 compared to control cells. MUC4 overexpression leads to increased (0.1%) side population (SP) and CD133-positive cancer stem cells compared to the control cells. Interestingly, the tumor sphere type circular colony formation was observed only in the MUC4 overexpressed ovarian cancer cells. Furthermore, the cancer stem cell marker CD133 was expressed along with MUC4 in the isolated circular colonies as analyzed by both confocal and western blot analysis. HER2 and cancer stem cell

specific marker ALDH1 along with Shh, a self-renewal marker, showed increased expression in the isolated circular colonies compared to MUC4-transfected cells.

Conclusion: These studies demonstrate that MUC4 overexpression leads to an enriched ovarian cancer stem cell population either directly or indirectly through HER2. In future, this study would be helpful for MUC4-directed therapy for the ovarian cancer stem cell population.”
“Objectives: Wennberg proposed the “”practice RepSox supplier style factor”" to explain the large LY-374973 variations in the use of medical care. As a corollary, we propose the “”leadership style factor”" of the director of the city/county

bureau of public health to explain changes in geographic variation in the uptake of cervical cancer screening.

Methods: We first calculated the triennial Pap smear rates for women aged 30-69 years from 1997 through 2010 for each city/county in Taiwan and the rate difference and rate ratio between the highest and the lowest city/county to illustrate the geographic variation in the uptake of cervical cancer screening. We then created an expert panel to conduct a hypothesis generation process to examine the possible effects of “”leadership style factors”" in explaining the changes.

Results: The Pap smear rate in Taiwan as a whole was 35% in 1997 and increased to 56% in 2001, and was then stable until 2010 (55%). In 2002, the geographic variation in the Pap smear rate was the smallest, ranging from 49% in Penghu County to 63% in I-lan County, with a rate ratio of 1.28. Unfortunately, the rate ratio increased to 1.49 in 2010, the rate being lowest in Penghu County (42%) and highest in Tainan City (63%).

The O’Leary plaque index and periodontal biotype

were rec

The O’Leary plaque index and periodontal biotype

were recorded for each subject and 246 Astra Tech (R) Osseo-speedTM implants were radiographically analysed (123 placed in SPT patients and 123 in No SPT patients) at the time of loading and one year later, measuring marginal bone loss with the program Dental Studio NX 6.0 (R). The statistical analysis was performed with Windows SPSS, applying Pearson’s correlation index and the Kruskal-Wallis click here and U-Mann Whitney non-parametric tests.

Results: Six patients were found to have periimplantitis and sixteen mucositis. The survival rate was 99.59% (100% SPT and 99.18% No SPT). Mean bone loss was 0.39 mm (range [-0.71 - 8.05]). Among SPT patients, 95% of the implants had losses less than or equal to the mean (mean bone loss of 0.16 mm) compared to 53.7% for the No SPT group (mean bone loss of 0.62 mm). A statistically significant relationship was demonstrated between bone loss around the implant and the patient’s periodontal biotype and plaque index.

Conclusions: The marginal bone loss around implants in patients with treated chronic periodontitis is minimal if they are in a controlled SPT programme and there is individual control of plaque index. Moreover, the presence of a thin periodontal PF-6463922 solubility dmso biotype represents a risk factor for additional bone loss.”
“Continuous and indiscriminate

use of pesticides, especially in tropical countries for public health or agriculture purpose, has led many vector populations to become resistant to organochlorides, organophosphates, and even to carbamates and pyrethroids. Development of resistance by a vector population has been one of the reasons for the failure of the control measures in many countries. This investigation demonstrates the efficacy of piperonyl-butoxide (PBO) with deltamethrin, as pyrethroid insecticide, against the field-collected mosquitoe larvae of five species, Aedes aegypti, Anopheles culicifacies,

An. stephensi, An. vagus, and Culex quinqufasciatus, and two morphological variants of Cx. tritaeniorhynchus BI 2536 Cell Cycle inhibitor (type A from grand pools of Mysore city and type B from rice fields of Mandya district). For testing the synergistic effect of 13130, stock solutions of deltamethrin and PBO were mixed in 1:6 ratio. The synergistic ratio and the percent suppression in deltamethrin tolerance were calculated by using LC(50) values. From the results, it is clear that, PBO is an effective synergist with deltamethrin against all of species undertaken in this investigation. So, it is suggested that PBO is a good synergist in this area for decreasing the use of pesticides in environment in vector control. (C) 2008 Wiley Periodicals, Inc. Environ Toxicol 24: 19 24, 2009.”
“Objectives. To study the perinatal outcome among monochorionic diamniotic (MCDA) twin pregnancies with absent or reversed end-diastolic flow of the umbilical artery (UA-AREDF) at 16-20 weeks of gestation.


A report from the sub-Saharan Africa region shows that the number

A report from the sub-Saharan Africa region shows that the numbers of patients on dialysis and those diagnosed with chronic kidney disease (CKD) has increased significantly. Other ISN-sponsored programmes such as Continuing Medical Education

activities for physicians Selleckchem SBI-0206965 and community screening projects have had far-reaching positive effects. Government funding for a dialysis programme is well established in South Africa, but this funding is limited so that the numbers accepted for public dialysis are restricted. Consequently in the Western Cape province of South Africa, a ‘category system’ has been formulated to attempt to cope with this unacceptable and restrictive ruling.”
“Insights into the evolution of hemoglobins and their genes are an abundant source of ideas regarding hemoglobin function and regulation of globin gene expression. This article presents the CFTR inhibitor multiple genes and gene families encoding human globins, summarizes major events in the evolution of the hemoglobin gene clusters, and discusses how these studies provide insights into regulation of globin genes. Although

the genes in and around the alpha-like globin gene complex are relatively stable, the beta-like globin gene clusters are more dynamic, showing evidence of transposition to a new locus and frequent lineage-specific expansions and deletions. The cis-regulatory modules controlling levels and timing of gene expression are a mix of conserved and lineage-specific DNA, perhaps reflecting evolutionary constraint on core regulatory functions shared broadly in mammals and adaptive fine-tuning in different orders of mammals.”
“The Water Framework Directive (2000/60/EC) is an innovative piece of legislation aimed at protecting the quality of all continental and coastal waters in Europe through an ecological evaluation of the ecosystems. Since it is widely

acknowledged that the greater the ecological realism the greater the difficulty of its definition, we describe the different Citarinostat supplier uses of benthic organisms as a tool for assessing the quality of sediment in lakes. We review the responses from single species to the community. We focus on studies in the laboratory and in the field, and we also critically consider the use of predictive models for these evaluations.

Our discussion of the information collected underlines the importance of the relation between sensitivity of single species and contaminants. Moreover, the recent approach in developing mechanistic models to predict the response of natural communities seems to be particularly powerful for community ecology, and we strongly recommend more effort along these lines. (C) 2012 Elsevier Ltd. All rights reserved.”
“OBJECTIVE: To estimate the association between time of delivery after external cephalic version at term and the risk for cesarean delivery.

Several clinical observations have suggested an association betwe

Several clinical observations have suggested an association between bedwetting and developmental delays in motricity, language development, learning disability, physical growth, and skeletal maturation. The aim of the present study is to evaluate the prevalence

of fine motor coordination and visuomotor integration abnormalities in prepubertal children with PMNE.

Methods: The study population included 31 children (16 males, 15 females; mean age 8.14 years +/- 1.36 years), and the control group comprised 61 typical developing children (32 males, 29 females; mean age 8.03 years +/- 1.44 years). The whole population underwent a clinical evaluation to assess total intelligence quotient level, visuomotor integration (VMI) skills,

and motor coordination performance (using the Movement Assessment Battery this website for Children, or M-ABC).

Results: No significant differences between the two study groups were found for age (P = 0.725), gender (P = 0.886), z-body mass index (P = 0.149), or intellectual abilities (total intelligence quotient) (P = 0.163). The PMNE group showed a higher prevalence of borderline performance on M-ABC evaluation and in pathologic performance on VMI Total Task compared to controls (P < 0.001). No significant differences between the two study groups ABT-263 nmr were found for pathologic performances selleck screening library on the M-ABC (P = 0.07), VMI Visual Task (P = 0.793), and VMI Motor Task (P = 0.213).

Conclusion: Our findings pinpointed that PMNE should not be considered as a voiding disorder alone and, consequently, the children affected should be referred to specific rehabilitative programs that aim to improve motor coordination and visuomotor integration.”
“Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occur in the setting of pancreatic disease. The most common pancreatic disorders associated with pancreatic panniculitis are acute and chronic pancreatitis, especially the alcohol-related

types and pancreatic carcinoma. We now report a case of pancreatic panniculitis in which skin eruptions, not abdominal symptoms, were the presenting symptom. A 45-year-old man presented with multiple erythematous tender subcutaneous nodules on the shins, arthralgia of both ankles and swelling of the left foot. He was diagnosed as having pancreatitis 15 months ago. Histopathologic findings of a skin biopsy showed focal fat necrosis with anucleated “”ghost-like”" fat cells with a thick shadowy wall. Laboratory evaluation revealed an increase in serum amylase and lipase. We diagnosed this patient’s problem as pancreatic panniculitis associated with a relapse of pancreatitis.

TEM micrographs show a transition from nanosized particles to clu

TEM micrographs show a transition from nanosized particles to cluster formation with increase in phosphor concentration. The green long-lasting phosphorescence of the composites was observed in the dark after removal of the excitation light. Photoluminescence (PL) was observed in the composites

of both polymers for phosphor volume concentrations above 1.0% for PMMA JNJ-26481585 and above 0.5% for LDPE. For each of these samples, a broad PL peak at about 505 nm wavelength was observed after excitation at 350 nm with a xenon lamp. For the LDPE composites, the DSC results show that the presence of the phosphor in the polymer has no major influence on either the melting temperature or enthalpy values of the polymer. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 117: 2635-2640, 2010″
“This study examined two issues. One, whether individuals with possible substance use disorders were more likely to be admitted to specialized chemical dependency

(CD) treatment after receiving a brief intervention (BI) – either alone or in combination with other services – than similar individuals who did not receive a BI. Two, whether participation in brief treatment (BT) following a BI was helpful in facilitating admission to CD treatment. The study took place in the emergency ISRIB research buy department (ED) of a large urban safety-net hospital where CD professionals screened patients for alcohol/drug problems and provided BI, BT, and referral to specialized CD treatment when appropriate (SBIRT). Substance use disorders were indicated by alcohol/drug problems noted in administrative records. Hospital records were used to match patients with likely substance use disorders who received BI with similar ED patients who had not been screened. Admission to publicly GSK2245840 supplier funded CD treatment was determined by matching

patient identifiers to state administrative records of CD treatment. Results indicated that individuals with a likely substance use disorder who received a BI (regardless of subsequent participation in BT) were significantly more likely to enter specialized CD treatment in the subsequent year than similar individuals who did not receive a BI. This result was particularly pronounced for patients with no CD treatment in the past two years. Results also indicated that participation in BT facilitated admission into CD treatment. The results suggest that SBIRT programs could serve an important role in increasing entry to specialized treatment for individuals with substance use disorders. (c) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Background: Widespread use of recombinant human bone morphogenetic protein (rhBMP) in cervical spine surgery has continued despite the U.S. Food and Drug Administration’s 2008 notification regarding its adverse effects.