\n\nData collection and analysis: Two authors independently extracted data and assessed risk of bias.\n\nMain results: We identified four cluster-RCTs (C-RCTs)

(n = 7558) and one cohort (n = 12742) of influenza vaccination for HCWs caring for individuals >= 60 in LTCFs. Pooled data from three C-RCTs showed no effect on specific outcomes: laboratory-proven www.selleckchem.com/products/Erlotinib-Hydrochloride.html influenza, pneumonia or deaths from pneumonia. For non-specific outcomes pooled data from three C-RCTs showed HCW vaccination reduced ILI; data from one C-RCT that HCW vaccination reduced GP consultations for ILI; and pooled data from three C-RCTs showed reduced all-cause mortality in individuals >= 60.\n\nAuthors’ conclusions: No effect was shown for specific outcomes: laboratory-proven influenza, pneumonia and death from pneumonia. An effect was shown for the non-specific outcomes of ILI, GP consultations for ILI and all-cause

mortality in individuals >= 60. These non-specific outcomes are difficult to interpret because ILI includes many pathogens, and winter influenza contributes < 10% to all-cause mortality in individuals >= 60. The key interest NU7441 in vitro is preventing laboratory-proven influenza in individuals >= 60, pneumonia and deaths from pneumonia, and we cannot draw such conclusions. The identified studies are at high risk of bias. Some HCWs remain unvaccinated because they do not perceive risk, doubt vaccine efficacy and are concerned about AZD9291 order side effects. This review did not find information on co-interventions

with HCW vaccination: hand washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, anti-virals, and asking HCWs with ILI not to work. We conclude there is no evidence that vaccinating HCWs prevents influenza in elderly residents in LTCFs. High quality RCTs are required to avoid risks of bias in methodology and conduct, and to test these interventions in combination.”
“In order to assess immunity to rubella in Izmir, Turkey, a total of 600 persons of 1-70 y of age were selected with cluster sampling. Of the 597 subjects, 120(20.1%) was susceptible to the rubella according to their serum antibody levels. Of children 1 to 6 y of age, 50.9% was found to be serologically susceptible to rubella. Rubella protection rates showed a age-related increase, reaching maximum in the 15-19 age group, in which 98.1% of these subjects had antibody titer above the full protective level. Of the 126 females in the reproductive age group, only 4(3.1%) were found to be serologically susceptible to rubella. Logistic regression analysis showed that among the several independent variables, only age (p < 0.001) was significantly associated with rubella protective antibody levels.

A distinctive Vancouver Island morphotype is very weakly differentiated, and does not appear to be reproductively MG-132 in vivo isolated from plants of the normal morphotype. The intercontinental geographical range of S.miyabeanum reflects recent and probably ongoing migration, facilitated by the production of tiny spores capable of effective long distance dispersal. The results of the present study are consistent with Pleistocene survival of S.miyabeanum in unglaciated Beringia, although we cannot eliminate the possibility that the species recolonized Alaska from Asia more recently.(c) 2013 The Linnean Society of London, Biological Journal of the Linnean Society,

2014, 111, 17-37.”
“Airway management relates to the period of tracheal intubation, maintenance of endotracheal tube in situ, and finally extubation. Problems related to difficult extubation still pose significant challenge for both anesthesiologists and intensivists. This article reviews current approach to extubation strategy following difficult

intubation. Guidelines and algorithm may be helpful in order to ensure safe management of the patient during this delicate period of airway management.”
“Nuclear pore complexes (NPCs) are composed of several copies of similar to 30 different proteins Linsitinib cost called nucleoporins (Nups). NPCs penetrate the nuclear envelope (NE) and regulate the nucleocytoplasmic trafficking of macromolecules. Beyond this vital role, NPC components influence genome functions in a transport-independent manner. Nups play an evolutionarily conserved role in gene expression regulation that, in metazoans, extends into the nuclear interior. Additionally, in proliferative cells, Nups play a crucial role in genome integrity

maintenance and mitotic progression. AR-13324 Here we discuss genome-related functions of Nups and their impact on essential DNA metabolism processes such as transcription, chromosome duplication, and segregation.”
“All current metallic vascular prostheses, including stents, exhibit suboptimal biocompatibility. Improving the re-endothelialization and reducing the thrombogenicity of these devices would substantially improve their clinical efficacy. Tropoelastin (TE), the soluble precursor of elastin, mediates favorable endothelial cell interactions while having low thrombogenicity. Here we show that constructs of TE corresponding to the first 10 (“N10″) and first 18 (“N18″) N-terminal domains of the molecule facilitate endothelial cell attachment and proliferation equivalent to the performance of full-length TE. This N-terminal ability contrasts with the known role of the C-terminus of TE in facilitating cell attachment, particularly of fibroblasts. When immobilized on a plasma-activated coating (“PAC”), N10 and N18 retained their bioactivity and endothelial cell interactive properties, demonstrating attachment and proliferation equivalent to full-length TE. In whole blood assays, both N10 and N18 maintained the low thrombogenicity of PAC.

In 13 cases, clinical rejection of the pancreas was diagnosed simultaneously, and two of these were biopsy proven SF 1101 and were positive for C4d immunostaining. Multivariate analysis identified only one significant risk factor: Female patients were three times more likely to experience AMR. Nearly all early episodes resolved with

treatment and did not predict graft loss, but multivariate Cox models revealed that late AMR episodes more than tripled the risk for kidney and pancreas graft loss; therefore, new strategies are needed to prevent and to treat late AMR in simultaneous pancreas-kidney transplant recipients.”
“The repeated frequency of microsatellite instability (MSI) in ovarian cancer (OC) ranges from 0% to 50%. Most MSI studies including OC patients have involved relatively small number of tumors, a wide range of different MSI markers, different patient characteristics, and varying criteria for defining tumors

as MSI positive. Thus, no conclusive evidence about MSI occurrence in OC has been provided and the large variation has made interpretation of these previous studies difficult. The majority of MSI studies have been performed on OC cases with few borderline ovarian tumor (BOT) cases included. Few BOT studies showed no Selleckchem DMH1 evidence of MSI, but in one study the frequency of MSI was 27.7% with all tumors of serous type, suggesting that MSI may play a role in the development of serous BOT. The aim of

our study was to determine the frequency of MSI using a panel of 16 dinucleotide markers: TP53, D17S250, CACNLB1, D18S58, D19S49, DXS538, DXS454, D5S117, D5S107, D6S284, D6S305, D9S171, D9S15, D11S554, D11S29, and D13S272 in tissue from patients with OC or BOT and to correlate the presence of MSI at these markers with the clinical information, such as FIGO stage, histological type, age, and survival in OC. The overall frequencies of MSI were within 2-10%. We observed MSI at different loci and with different extent (2.3-9.8%) in the different histopathological types. In both BOT and OC cases, we observed that all high Selleck Alvespimycin MSI (MSI-H) were of serous type. No significant difference in disease specific survival was found between stage III/IV OC patients who presented MSI compared to patients being microsatellite stable (MSS) (p = 0.72). In conclusion, we found no association to any of the clinical parameters evaluated, although a tendency of a higher frequency of MSI was observed among serous OC.”
“Background: Resveratrol has been reported to have potential chemopreventive and apoptosis-inducing properties in a variety of tumor cell lines. Objective: In this study, to investigate the effects of resveratrol on protein kinase C (PKC) activity and apoptosis in human colon carcinoma cells, we used HT-29 cells and examined the PKC alpha and ERK1/2 signaling pathways.

e., HOMA-IR, QUICKI) did not differ between Hp+ and Hp-subjects (all P > 0.42). However, Hp+ subjects showed significantly higher triglyceride levels and a higher total chloesterol-to-HDL ratio but lower sex-hormone binding globulin (SHGB) levels than Hp-subjects (all P <= 0.05).\n\nConclusion: While our results obtained in European severely obese patients

do not provide evidence for an enhanced IR state associated Napabucasin in vivo with gastric Hp infection, they suggest that the presence of the bacterium in gastric biopsies is associated with an adverse lipid profile and reduced SHGB levels.”
“A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal selleck screening library cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges

for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. CX-6258 mw In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researdhers to create the necessary

scientific and clinical network to advance the rate of progress and impact of the research. (C) 2013 Elsevier Inc. All rights reserved.”
“Surgical excision combined with radio-chemotherapy represents the gold standard of therapy of medulloblastoma. The effectiveness of such a combined treatment has encouraged the use of radiotherapy even in young paediatric patients, in spite of the many adverse effects reported in literature, and, in particular, the increased risk of a second radioinduced malignancy. Irradiation is the well-known risk factor for development of benign and malignant thyroid tumours. Children are more exposed to this risk because of their thyroid gland is more sensitive to carcinogenic effect of ionising radiation.

\n\nMethods. Sixty subjects, all successful contact lens wearers, were seen on two visits. Meibum was collected from the lower lid of the right eye with a glass microcapillary tube, and with a Dacron swab, cytology microbrush, or spatula from the left eye. Extraction with 2: 1 chloroform: methanol was done either immediately or after data collection was complete. Individual samples were divided into four equal aliquots for analysis of total lipids, cholesterol, and inorganic phosphates by assay-based techniques. Effects of collection method, extraction, and dry eye status were examined using repeated measures analysis of variance and logistic Vorinostat regression.\n\nResults. Total lipids showed

significance for collection device (p < 0.0001) but not for extraction technique (p = 0.13) or dry eye status (p = 0.97). Dacron swab collection SB203580 cost was associated with more total lipid on average than each other collection device (p < 0.0001). The cholesterol assay showed significance of collection device (p < 0.0001) and extraction technique (p = 0.0002) but not dry eye status (p = 0.55). Spatula collection was associated with more cholesterol on average than each other collection device (p < 0.0001). For inorganic phosphates, immediate extraction (p < 0.0001), cytology microbrush collection (p < 0.0001), and non-dry eye status (p = 0.03) were associated

with the greater likelihood of detection.\n\nConclusions. Dacron swab collection was associated with the highest average amount of total lipid detected, whereas spatula collection and immediate extraction was associated P505-15 purchase with the highest average amount of cholesterol detected. Cytology microbrush collection with immediate

extraction on non-dry eye subjects was associated with the highest probability of detection of inorganic phosphates. (Optom Vis Sci 2011; 88: 525-533)”
“There are a limited number of Food and Drug Administration (FDA)-approved medications for the treatment of autism. Meanwhile, oxidative stress and neuroinflammation are supposed to play a causative role in autism. N-acetylcysteine may provide cystine, a precursor for glutathione (GSH), which is an important antioxidant factor in the brain. We here report a child with autism, whose symptoms were markedly decreased after taking oral N-acetylcysteine 800 mg/day, in three divided doses. His social interaction was significantly increased. The score of social impairment on a visual analog scale decreased from 10 to 6 in the two-month trial. The aggressive behaviors decreased from 10 to 3. This case suggests that N-acetylcysteine may decrease some symptoms of autism.”
“We analyzed the within-site spatial heterogeneity of microbial community diversity, polyaromatic hydrocarbon (PAH) catabolic genotypes, and physiochemical soil properties at a creosote contaminated site.

In early spring 2008 mid-side cashmere samples were taken from 719 cashmere adult females, and 41 cashmere adult males and castrates. Samples came from 53 villages and a total of 156 farmers’ flocks. For 91 goats from 33 farmers in 13 villages of two districts that had been sampled earlier, cashmere was combed from the goat at the time of a second visit

(end of April 2008) when the cashmere would normally be harvested. RWJ 64809 Following standard cashmere objective measurement, data were examined using general linear modelling to quantify the effects of potential determinants. The mean fibre diameter (MFD) of cash-mere differed between provinces (Osh 15.7 mu m, Naryn 16.7 mu m; P = 4.4 x 10(-20)). About 42% of the cashmere was <16 mu m, 48% was 16.0-18.0 mu m and 9.5% was >18.0 mu m. Most of the cashmere samples were Coloured (81%), with 63% black and 19% white. The percentage of cashmere samples that were white declined as MFD

increased (26% < 14 mu m to 11% of > 18 mu m). The primary determinants of cashmere MFD of individual goats were age of goat (range 1.46 mu m, P Baf-A1 = 1.8 x 10(-12)) and farm (range 6.5 mu m, P = 1.7 x 10(-14)). The lesser effects detected for sex (range 0.9 mu m, P = 0.026) and colour of cashmere (range 1.8 mu m, P = 0.023) were based on small sample sizes and are unreliable. Age of goat had important affects on fibre diameter variation (up to 1.7% in coefficient of variation, P = 5.8 x 10(-6)) and fibre curvature (2.5-5 degrees/mm, P = 2.1 X 10(-4)). By far the greatest effect on fibre curvature was cash-mere MFD (P = 3.0 x 10(-104)) with a smaller effect of sex (about 5 degrees/mm. P = 3.0 x 10(-6)). Village effects were detected on fibre diameter variability GDC-0068 (range 4.5% in coefficient of variation, P = 0.027) and fibre curvature (range 15 degrees/mm, P = 1.6 x 10(-7)). There was a strong negative association between increasing MFD and declining fibre curvature (-5.11 +/- 0.181 degrees/mm per 1 mu m; P = 7.1 X 10(-121); r(2) = 0.51). Average combed cashmere weight was 164 g, the clean cashmere

content was 0.661 and median clean cashmere production was 110 g per goat (range 60-351 g). Combed cashmere production increased with altitude of the village, probably related to different moulting times as spring temperatures warmed up later in higher altitude villages up to 3200 masl. Measurements of combed cashmere MFD were coarser than the mid-side samples taken earlier in the year. There are farmers and cashmere goats in the sampled districts of Kyrgyzstan which produce the finest qualities of commercial cashmere as the vast majority of cashmere is fine. has low variation in fibre diameter and has fibre crimping (curvature) typical Of Chinese and Mongolian cashmere. There is substantial scope to increase the production and commercial value of cashmere produced by Kyrgyz goats.

Combining haemodynamic tests and imaging techniques best accomplish the investigation of these three aspects of the pathophysiology in CVI. The information obtained from ambulatory venous pressure and color duplex ultrasound is accurate PU-H71 when assessing reflux in the different segments of the different venous systems. The valve anatomic location and dynamic picture is supplied by descending phlebography. In case of venous obstruction, the haemodynamic tests lack accuracy and sensitivity. Therefore, imaging catheter techniques have to fill-in to depict vein morphology as well as inflow/outflow characteristics. The participation of several specialties in

the investigation of these patients widens the treatment possibilities by identifying those who may benefit from advanced surgical and/or endovascular procedures. This interventional-targeted approach should be a centralized function.”
“Purpose: Volumetric modulated arc therapy (RapidArc; Varian Medical Systems, Palo Alto, CA) allows fast delivery of stereotactic radiotherapy for Stage I lung tumors. We investigated discrepancies between

the calculated and delivered dose distributions, as well as the dosimetric impact of leaf interplay with breathing-induced tumor motion.\n\nMethods and Materials: In 20 consecutive patients with Stage I lung cancer who completed RapidArc delivery, 15 had tumor motion exceeding 5 mm Compound C on four-dimensional computed tomography scan. Static and dynamic measurements were performed with Gafchromic EBT film (International Specialty Products Inc., Wayne, NJ) in a Quasar motion phantom (Modus Medical Devices, London, Ontario, Canada). Static measurements were compared with calculated dose distributions, and dynamic measurements were compared with the convolution of static measurements with sinusoidal motion patterns. Besides

clinical treatment plans, additional cases were optimized to create excessive multileaf collimator modulation and delivered on the phantom with peak-to-peak motions of up to this website 25 mm. gamma Analysis with a 3% dose difference and 2- or 1-mm distance to agreement was used to evaluate the accuracy of delivery and the dosimetric impact of the interplay effect.\n\nResults: In static mode film dosimetry of the two-arc delivery in the phantom showed that, on average, fewer than 3% of measurements had gamma greater than 1. Dynamic measurements of clinical plans showed a high degree of agreement with the convolutions: for double-arc plans, 99.5% met the gamma criterion. The degree of agreement was 98.5% for the plans with excessive multileaf collimator modulations and 25 mm of motion.\n\nConclusions: Film dosimetry shows that RapidArc accurately delivers the calculated dose distribution and that interplay between leaves and tumor motion is not significant for single-fraction treatments when RapidArc is delivered with two different arcs. (C) 2011 Elsevier Inc.

(J Vasc Surg 2012;55:1008-14.)”
“Background: Comparative studies of genital human papillomavirus (HPV) among men having sex with men (MSM), men having sex with women and men (MSWM),

and men having sex with women (MSW) have not been conducted so far; however, such comparisons may be important for planning prevention strategies like vaccination.\n\nMethods: Men, aged 18 to 70 years, were enrolled in a study of genital HPV in Sao Paulo, Brazil; Cuernavaca, Mexico; and Tampa, Anlotinib in vitro FL. Men were classified as MSM (n = 170), MSWM (n = 214), and MSW (n = 3326) based on self-reported sexual behavior. Genotyping for HPV was conducted on cells from the penis and scrotum. Prevalence data were adjusted by country. Factors potentially associated with genital HPV were assessed using multivariable Poisson regression.\n\nResults: Genital HPV prevalence was typically higher among MSWM than among MSM or MSW for groups of HPV genotypes including nononcogenic types (51%, 36%, and 42%, respectively), and multiple types (37%,

24%, and 29%, respectively). Age and alcohol consumption in the past month were associated with oncogenic HPV among both MSM and MSWM; however, there were no statistically significant associations between sexual behaviors and genital HPV among MSM or MSWM.\n\nConclusions: Prevalence of genital HPV may be higher among MSWM than among MSW or MSM. Number Elacridar purchase of female sex partners was associated with genital HPV among MSW, but number

of male anal sex partners was not associated with genital HPV among MSM and MSWM.”
“Libyostrongylus sp. are nematodes that infect ostriches. Libyostrongylus douglassii was first described in ostriches from several countries in the world. Later Libyostrongylus dentatus was morphologically identified in ostriches in the USA and Brazil, and mixed infection selleckchem is common in the latter country. The internal transcribed spacer (ITS) region of the ribosomal DNA gene is used for genetic variability assessment and phylogenetic reconstruction for many organisms. Through genetic analysis the status of different species morphologically defined was confirmed and a molecular method was developed to differentiate both species. ITS1, 5.8S, ITS2 regions of L. douglassii and L dentatus were characterized. Regarding complete ITS region, the K2-p genetic distance between the species was 0.060 (SE 0.008) and the intra-specific distance was 0.002 (SE0.001) for L. dentatus and 0.006 (SE 0.002) for L.douglassii. NJ and MP phylogenetic analysis of ITS1 and ITS2 regions indicated that both species belong to the Trichostrongylidae family, and are evolutionarily different, suported by high bootstrap value. Based on ITS DNA polymorphisms, a molecular approach was designed to detect both species. These results are the first molecular characterization of L.

\n\nMethods: Thermographic images of 55 patients with primary RP (PRP, n = 27) and systemic sclerosis (SSc, n=28) who had undergone assessment of RP were retrospectively reviewed. The DDD for individual Selleck CHIR98014 digits, and composite scores of multiple digits, were calculated at baseline (23 degrees C), and at 10 min following CST. The discriminatory capacity of the mean DDD, and the

proportion of patients with a clinically meaningful DDD of <-1 degrees C, were assessed for individual digits and composite indices, at baseline and following cold challenge.\n\nResults: There was a more pronounced decrease of the DDD (indicating reduced distal perfusion) following CST in patients with PRP compared to SSc. The disparity Taselisib purchase in response to CST between groups narrowed the differences that were present at baseline, reducing the discriminatory capacity

of the DDD for all endpoints. Sparing of the thumbs occurs to a greater extent in SSc (P<0.005) compared with PRP (P<0.05) but does not facilitate differentiation between groups. Large variability of the DDD within groups precludes easy differentiation between disease states. Composite indices of multiple digits are preferable to individual digital assessment.\n\nConclusions: The discriminatory capacity of the DDD is lost following CST. The CST may not be essential in the thermographic assessment of RP, potentially allowing greater use of thermography in clinical practise. (C) 2011 Elsevier Inc. All rights reserved.”
“Pseudomonas chlororaphis phage 201 phi 2-1 is a relative of Pseudomonas aeruginosa myovirus buy GSK1120212 ( KZ. Phage 201 phi 2-1 was examined by complete genomic sequencing (316,674 bp), by a comprehensive

mass spectrometry survey of its virion proteins and by electron microscopy. Seventy-six proteins, of which at least 69 have homologues in ( KZ, were identified by mass spectrometry. Eight proteins, in addition to the major head, tail sheath and tail tube proteins, are abundant in the virion. Electron microscopy of 201 phi 2-1 revealed a multitude of long, fine fibers apparently decorating the tail sheath protein. Among the less abundant virion proteins are three homologues to RNA polymerase beta or beta’ subunits. Comparison between the genomes of 201 phi 2-1 and phi KZ revealed substantial conservation of the genome plan, and a large region with an especially high rate of gene replacement. The phi KZ-like phages exhibited a two-fold higher rate of divergence than for T4-like phages or host genomes. (C) 2008 Elsevier Inc. All rights reserved.”
“This review focuses on the possibilities and limits of nontarget screening of emerging contaminants, with emphasis on recent applications and developments in data evaluation and compound identification by liquid chromatography-high-resolution mass spectrometry (HRMS).

9%, and the diagnostic specificity was 92.7%, using 2 serum features and CA 19-9 serum concentration. Healthy controls were differentiated from patients with PC and chronic pancreatitis, with the use of 3 features of the peptidome (diagnostic sensitivity, 98.2%; diagnostic specificity, 97.1%).\n\nConclusions: Standardized serum

peptidome profiling could be a useful tool to improve biochemical diagnosis of PC in combination with the classic tumor marker, CA 19-9.”
“Objective: A National Institute on Aging sponsored work group on preclinical Alzheimer’s disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD.\n\nMethods: Seventy-one apolipoprotein E (APOE) epsilon 4 homozygotes, 194 epsilon 3/epsilon 4 heterozygotes, and 356 epsilon 4 noncarriers age 21 to 87 years who were cognitively healthy underwent this website neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups.\n\nResults: There was a significant effect of age on all cognitive domains in both APOE epsilon 4 carriers and noncarriers. A significant effect of APOE epsilon 4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional

comparisons did not discriminate the groups.\n\nConclusions: Although cognitive aging patterns are similar in APOE epsilon 4 carriers and noncarriers, preclinical AD is characterized by a significant buy VS-6063 see more epsilon 4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design. (C) 2014 The Alzheimer’s Association. All rights reserved.”
“A survey of epiphytic bryophytes within a tree was conducted in lower montane rainforest at 2400 m in the Peruvian Yungas. The Weinmannia sp. host tree supported 110

species (77 hepatics, one hornwort and 32 mosses). To our knowledge, this is the highest single-tree bryophyte species richness reported to date. We used Johansson zones (lower trunk, upper trunk, mid-crown, mid-outer crown and outer crown) to stratify our sampling and found that the greatest species richness and abundance was on the upper trunk and large branches of the mid-crown. Hepatics, and the Lejeuneaceae in particular, were dominant in all five Johansson zones of the tree. The mid-crown had higher radiation intensity than the dark lower trunk while still having high relative humidity. Non-metric multidimensional scaling indicated the presence of four communities: an outer crown, a mid to mid-outer crown, an upper trunk and a lower trunk community. The outer crown supported only two moss species along with 35 hepatics, which included 17 high-light tolerant hepatics. The climate data suggested that this pattern was due to higher irradiation and exposure.