Summary

Although early results of phase I focal therapy trials are encouraging, long-term oncological outcomes remain to be elucidated. Incorporation of these technological advances into large prospective trials is needed to establish focal therapy as an important asset in the urologist’s armamentarium against prostate cancer.”
“Objectives: To assess the development of face and hyoid bone in children with obstructive sleep apnea syndrome (OSAS) through lateral cephalometries.

Materials

JAK inhibitor and methods: Children aged 7-10 years with mixed dentition and with no previous otorhinolaryngologic, orthodontic or speech therapy treatments were studied. Twenty nasal breathers were compared to 20 mouth breathing children diagnosed as OSAS patients. All children underwent otorhinolaryngologic evaluation and cephalometries; children with OSAS also underwent nocturnal polysomnography in a sleep laboratory.

Results: Children with OSAS presented increase in total and lower anterior heights of the face when compared to nasal breathers. In addition, children with OSAS presented a significantly more anterior and inferior position of the hyoid bone than nasal breathers. No significant differences in upper, anterior or posterior heights of the face were observed between groups.

Conclusion: The results suggest that there are evident and early changes in facial growth and development among children with OSAS, characterized by increased total and inferior anterior

heights of the face, as well as more anterior and inferior position of the hyoid bone. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“The Xylitol for Adult Caries Trial was a three-year, check details double-blind, multi-center, randomized clinical trial that evaluated the effectiveness of xylitol vs. placebo lozenges in the prevention of

dental caries in caries-active adults. The purpose of this secondary analysis was to investigate whether xylitol lozenges had a differential effect on cumulative caries increments on different tooth surfaces. Participants (ages 21-80 yrs) with at least one follow-up visit (n = 620) were examined at baseline, 12, 24, and 33 months. Negative binomial and zero-inflated negative binomial regression models were used to estimate incidence rate ratios (IRR) for xylitol’s differential effect on cumulative caries Epoxomicin supplier increments on root and coronal surfaces and, among coronal surfaces, on smooth (buccal and lingual), occlusal, and proximal surfaces. Participants in the xylitol arm developed 40% fewer root caries lesions (0.23 D2FS/year) than those in the placebo arm (0.38 D2FS/year; IRR = 0.60; 95% CI [0.44, 0.81]; p < .001). There was no statistically significant difference between xylitol and control participants in the incidence of smooth-surface caries (p = .100), occlusal-surface caries (p = .408), or proximal-surface caries (p = .159). Among these caries-active adults, xylitol appears to have a caries-preventive effect on root surfaces (ClinicalTrials.gov NCT00393055).

Audit results produce tangible evidence that is useful when applying for capital expenditure. Light measurements are not easy to make. There needs to be a convenient device to reliably measure laryngoscope illumination.”
“Microparticles are small membrane vesicles released from activated cells and are associated with thrombosis and inflammation. Microparticles contain a unique subset Of surface proteins derived from the parent cell

and may be responsible selleck for their diverse biological functions. To identify these proteins, juvenile baboons (Pap,io anubis, n = 4) underwent iliac vein thrombosis with 6-hour balloon Occlusion. Plasma samples were taken at baseline and at 2 clays postthrombosis for microparticle analysis. Microparticles were extracted from platelet-poor plasma, digested separately with trypsin and tagged using isobaric tagging for relative and absolute quantitation find more reagents. The digests were Subjected to 2-dimensional liquid chromatographic separation followed by matrix-assisted laser desorption/ionization tandem mass spectrometry. Peak lists were generated and searched against all primate sequences. For protein identity, a minimum of 2 peptides at 95% confidence interval was required. Later, isobaric tagging for

relative and absolute quantitation ratios were generated comparing relative protein level of day 2 to baseline. The proteomic analysis was performed twice for each blood sample, totaling 8 experiments. Proteins were considered elevated or depressed if the isobaric tagging for relative and absolute quantitation ratio deviated by 20% change from normal and a P value less than .05. Significantly, 7 proteins were differentially expressed on day 2 compared to baseline, and appeared in at least 3 animals and regulated in

at least 4 experiments. Among these 7 proteins, upregulated proteins include various forms of fibrinogen and alpha-1-antichymotrypsin and downregulated proteins include immunoglobulins. These proteins influence thrombosis and inflammation through hemostatic plug formation (fibrinogen), inhibiting neutrophil adhesion (alpha-1-antichymoptrypsin), and immunoregulation (immunoglobulins). Further Studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis.”
“Background: To investigate the pathogenesis of diabetic nephropathy (DN) and to search for LY2090314 PI3K/Akt/mTOR inhibitor novel therapeutic targets, the glomerular protein expression profile of KKAy mice treated by losartan was analyzed by two-dimensional differential gel electrophoresis (2D-DIGE).

Methods: The eight-week-old KKAy mice were divided into the losartan treatment group and the non-treatment group, and C57BL/6 mice were used as the control group. After 12 weeks treatment, glomeruli were isolated by abdominal perfusion with magnetic beads, and the glomerular proteins were extracted. The glomerular protein expression profiles were investigated using 2D-DIGE and MALDI-TOF mass spectrometry.

The difference to previous synthetic attempts is the high charge of the dextran coating, which according to our

study maintains the colloidal stability and good dispersion of the selleck inhibitor ferrofluid during the magnetic heating stage. Specifically, in vitro 2 mu l of the ferrofluid gives an outstanding temperature rise of 33 degrees C within 10 min, while in vivo treatment, by infusing 150 mu l of the ferrofluid in animal model (rat) glioma tumors, causes an impressive cancer tissue dissolution. (C) 2010 American Institute of Physics. [doi:10.1063/1.3449089]“
“Objectives: To describe our experience and clinical outcomes with the management of pediatric tympanostomy tube otorrhea secondary to methicillin-resistant Staphylococcus aureus (MRSA).

Methods: Retrospective review of pediatric patients (age <18) diagnosed with culture-positive MASA tympanostomy tube otorrhea.

Results: MRSA positive ear cultures in the presence of tympanostomy tubes were identified in 41 patients (6.3%). The average selleck kinase inhibitor age was 2.9 years old. In all cases, culture results indicated sensitivity to trimethoprim/sulfamethoxazole and gentamicin; resistance to fluoroquinolones and clindamycin occurred in 87.8% and 61.0% of cases, respectively. Fluoroquinolone and sulfacetamide ototopical medications were found to be associated with successful

otorrhea resolution (p = 0.005 and 0.009, respectively). Adjunctive therapy with oral antibiotics, bactrim and clindamycin (p = 0.172 and 0.877, respectively), did not improve resolution rates

with medical treatment. Tympanostomy tube removal was more successful than medical therapy Nocodazole alone (p < 0.0001).

Conclusion: Appropriately treated recurrent or recalcitrant tympanostomy tube-related otorrhea should raise the suspicion for MRSA-related tympanostomy tube otorrhea. Fluoroquinolone ototopical medication should be considered for initial therapy. Sulfacetamide ototopical medication can be considered for failures. The adjunctive use of oral antibiotics, bactrim and clindamycin, and aminoglycoside ototopical medications did not improve clinical outcomes for medical therapy alone. We believe that some consideration be given to removal of the tympanostomy tube with or without replacement, after an initial treatment period with fluoroquinolone and/or sulfacetamide otopical medications. Our findings seem to suggest an improved rate with tympanostomy tube removal over medical therapy alone (p < 0.0001). No standard management guidelines currently exist. (C) 2012 Elsevier Ireland Ltd. All rights reserved.”
“Dielectrophoresis (DEP) is employed to differentiate clones of mouse melanoma B16F10 cells. Five clones were tested on microelectrodes. At a specific excitation frequency, clone 1 showed a different DEP response than the other four.

In this review, we provide an overview regarding the literature on laparoscopic liver resection for benign and malignant liver tumors with the aim to discuss the current standards and define remaining

challenges. Although numerous case series and meta-analyses have addressed the evolving field of laparoscopic liver surgery recently, data from randomized controlled trials are still AP24534 not available.

Laparoscopic liver resection is feasible and safe in selected patients and experienced hands. Even major liver resections can be performed laparoscopically. The minimal invasive approach offers benefits in perioperative short-term outcome without compromising oncological outcomes compared to open liver resections. Further randomized trials are needed to formally prove these statements and to define the optimal indication and techniques for the individual patient.”
“The criteria adopted for establishing

whether a determined substance has potential as a cosmetic constituent are based on the present legislation of each country. In this study, natural antiaging constituents as Fomes officinalis, rice protein and glutamic acid were pharmacologically evaluated using neuromuscular preparation. These constituents induced a neuromuscular blockade, individually LCL161 solubility dmso and also in mixture, simulating a Botox (R), but not, dimethylaminoethanol-effect. The pharmacological knowledge is beneficial MK-8931 since the real effect of each ingredient becomes apparent, increasing the consumer’s confidence on the antiaging cosmetic.”
“Pancreatic surgery is technically complex and requires considerable expertise. Laparoscopic pancreatic surgery adds the need for considerable experience with advanced laparoscopic techniques. Despite the technical difficulties, an increasing number of centers propagate the use of laparoscopy in pancreatic surgery over the last decade.

In this review, we provide an overview of the literature regarding the advantages and disadvantages of laparoscopic pancreatic surgery. Larger prospective randomized studies have emerged in the subset of laparoscopic or

retroperitoneoscopic surgery for acute pancreatitis, considerable single center experience has been reported for laparoscopic pancreatic tail resection, and laparoscopic pancreatic head resection, however, is still restricted to a few experienced centers worldwide.

Laparoscopic pancreatic surgery is becoming more and more established, in particular for the treatment of benign and premalignant lesions of the pancreatic body and tail. It has been shown to decrease postoperative pain, narcotic use, and length of hospital stay in larger single center experience. However, prospective trials are needed in laparoscopic resective pancreatic surgery to evaluate its advantages, safety, and efficacy in the treatment of pancreatic neoplasms and in particular in malignant pancreatic tumors.

Patients with a previous biopsy of NMSC who presented for treatment were eligible.

A self-administered questionnaire assessed what patient perceptions of lesions diagnosed as NMSCs had been before they were aware of the diagnosis. Medical records were reviewed for tumor type, size, and location.

ResultsOne hundred sixty-three consecutive patients undergoing Selleckchem Taselisib treatment for NMSC completed the questionnaire. The most common initial impressions of the lesion were skin cancer (20%), acne (19%), sore (10%), unknown (9%), dry skin (7%), age spot (6%), and injury (6%). Seventy-two percent of patients were the first to notice the lesion. Patients with a history of skin cancer were more likely to think the lesion was a skin cancer on initial SBE-β-CD mw impression (28% vs 8%) (p<.001).

ConclusionsUnderstanding how patients perceive their skin cancers may aid in targeting educational strategies and increase awareness of skin cancer risk. Our data suggest that there are important subtleties in self-identification that may need to be taken into consideration in any educational campaign targeting NMSC.”
“Diffusion

coefficients (D) of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) were determined by film-stacking technique in low-density polyethylene (LDPE) and two types of polydimethylsiloxane (PDMS) (also known as silicone rubber, SR) with the trade names AlteSil (TM) and Silastic. The estimated values of D for PCBs and PAHs over a wide range of hydrophobicity were 2-2.5 orders of magnitude lower in LDPE than in SR polymers. Log D (m(2) s(-1)) of PCBs ranged from -10.1 to -10.9 for SRs and from -12.4 to -13.7 for LDPE. For PAHs these ranges were -9.8 to -11.4 for SRs and -11.9 to -13.7 for LDPE. Compared with the D values calculated in water, D were 1-2 and 3-4 orders of magnitude lower in SR and LDPE, respectively. For PAH molecules, D was lower than for PCBs with a similar molecular weight, probably because of their more rigid structure. The range of log D for PCBs in

SR was only 0.5 log units (factor of 3.2) versus 1.2 log units (factor of 16) in LDPE. Although compound classes showed different relations, a linear relation of D with total surface area was the most universal. This relation may be used for prediction of D values in SR and LDPE polymers for other organic compounds. (C) 201.0 Wiley Periodicals, Selleckchem ERK inhibitor Inc. J Appl Polym Sci 116: 1803-1810, 2010″
“SmNi5 and Sm(Ni, T)(5) [T=Co, Fe] epitaxial thin films with the c-axis perpendicular to the substrate surface are successfully prepared on Cu underlayers heteroepitaxially grown on MgO(111) single-crystal substrates. The nucleation behavior of SmNi5 and Sm(Ni, T)(5) crystals on Cu(111) underlayers were investigated. The SmNi5 and the Sm(Ni, Co)(5) films consist of two types of domains whose orientations are rotated around the film normal by 30 degrees each other, whereas the Sm(Ni,Fe)(5) film is a single crystal.

The information presented in this review should be useful in understanding the taxonomy, epidemiology, zoonotic potential, and importance in public health of E. bieneusi. Published by Elsevier Ltd.”
“The temperature and the speed of drying may affect the quality

of the end product of medicinal plants. In addition, ecotypes and chemotypes could be factors influencing this quality. Thus, the aim of our study was to explore various techniques of drying of Origanum syriacum L., which is considered as a main ingredient in the Lebanese diet. For all these reasons, we decided to study two types MK-1775 concentration of O. syriacum originating from Rkai and Ibrine regions on which analyses were carried out. In view of our results, a moderate temperature, in the absence of light, is more favourable for the safeguarding of the flavours and chlorophylls. On the other hand, these conditions seem to be unsuitable for other substances. Selleck BI 10773 In order to clarify the optimal conditions for drying of O. syriacum to lead to a product of quality, the choice of a technique of suitable dehydration seems to be delicate.”
“The correlation between the recoil loop openness and the activation volume has been studied for the SmCo5/alpha-Fe nanocomposite powder material prepared by mechanical alloying. The alpha-Fe phase content in the nanocomposite

powders was adjusted by varying the amount of alpha-Fe addition in raw materials and the postannealing temperature after mechanical alloying. It was found that the

recoil loop openness increases with increasing alpha-Fe phase content. More interestingly, there is a linear relation between the openness of recoil loops and the reciprocal activation Gilteritinib volume, indicating that the recoil loops are related to thermal fluctuation. The large open area of the recoil loops for nanocomposite magnets is attributed to the fact that low anisotropy in the alpha-Fe phase leads to unstable magnetization under thermal fluctuation. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3067850]“
“Shadow of prion protein is a gene potentially involved in the pathogenesis of prion diseases. However, the Shadoo protein encoded by this gene has not yet been studied in sheep, an important species in prion matters. Therefore, we developed a polyclonal antibody against ovine Shadoo and assessed the presence and distribution of this protein in the ovine brain by immunohistochemistry. The strongest staining level was found in the cerebellum (especially in the Purkinje cells) and in the pons, but cerebrum, hippocampus, pituitary gland, medulla oblongata, thalamus and hypothalamus were also immunopositive. Remarkably, a typical granular pattern was seen in most of the tested brain tissues, which might indicate that Shadoo is primarily expressed at synapses.

Accumulation of an internalized form of Sema3A is associated with degeneration

of neurons, making these molecules candidates for the development of AD. Single nucleotide polymorphisms (SNPs) rs36026860 and rs28469467 in Sema3A as well as rs13284404 and rs11526468 in Sema4D were analyzed in a population of 240 patients with AD compared with 222 age-matched controls. None of SNPs in Sema3A were present, either in patients or controls. The distribution of the Sema4D rs11526468 and rs13284404 SNPs was not significantly different between patients and controls, even stratifying for gender or age at onset. In silico analysis predicted that rs11526468 and rs28469467 are probably damaging. This high degree of conservation of Sema3A suggests a very important role for this protein. However, neither Sema3A nor Sema4D likely influence the susceptibility to AD.”
“Background: The human papillomavirus PF-6463922 price type selleck 8 (HPV8) is associated with the development of non-melanoma skin cancer. Transgenic mice expressing the complete early gene region of HPV8 (E6/E7/E1/E2/E4 = CER) or E6 separately under the control of the keratin14 promoter spontaneously developed papillomas characterized

by varying degrees of epidermal dysplasia. Papilloma growth could be synchronized by a single UVA/B irradiation of the skin, which led to the development of papillomas within three weeks.

Objective: The objective

of this study VX-765 mouse was to identify alterations in cellular gene expression correlated with HPV8 oncogene expression in transgenic mice.

Methods: We applied global gene expression profiling by microarray analysis and confirmed deregulation of cellular genes by qRT-PCR and immunohistochemical analysis.

Results: By comparison of non-lesional HPV8-CER skin with skin of the parental mouse strain FVB/n, two cellular genes, namely StefinA and Sprr2, coding for precursor proteins of the cornified envelope, were predicted to be strongly upregulated in transgenic skin, which could be confirmed in subsequent qRT-PCR experiments. StefinA and Sprr2 mRNA expression was enhanced until day 7 after UV treatment with higher levels in HPV8 positive skin. While the expression of both genes returned to a normal level in the course of epidermis regeneration in wt mice, the expression persisted elevated in hyperplastic transgenic skin. Staining of an UV induced papilloma of FVB/n wt mouse revealed also strong expression of StefinA and Sprr2 indicating that upregulation in later stages of papilloma formation is independent of HPV8.

Conclusion: In non-lesional HPV8-CER transgenic skin StefinA and Sprr2 were found to be indirect/direct transcriptional targets of HPV8. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Multivariable regression was used to assess trends between regional use and responses. We received 1210 responses (12%) and used 1124 after exclusions. Across regions, physicians were equally likely to recommend ICDs to males or females with ischemic (similar to 99% for both; P = NS) or nonischemic cardiomyopathy (85 vs. 88% P = 0.85). Significant increasing trends in the CH5183284 manufacturer probability recommending ICD therapy were found when the patient was “”frail”" (21% to 32%; P = .03) or had a life expectancy < 1 year (5% to 10%; P = .05).

These differences were not associated with attitudes toward ICDs.

Conclusions: Independent of variations in physicians’ attitudes towards ICDs, physicians in regions of low ICD use are not less likely to recommend ICDs in situations EPZ-6438 clearly supported by guidelines while those in regions of high ICD use are more likely to recommend ICDs to patients who might have limited benefit.

(J Cardiac Fail 2011;17:318-324)”
“A simplistic numerical kinetic model to predict the deposited film morphology in dusty plasma chemical vapor deposition reactors is developed. The morphological accretion of a circular object is studied in a two-dimensional geometry and the most important deposition phenomena are taken into account, i.e., surface diffusion and surface ion bombardment. Both isotropic and anisotropic plasmas are considered. It is shown that when the particle is located in an isotropic plasma, the deposited film maintains the original particle sphericity. Whereas, if the particle is assumed to levitate in the (pre) sheath forming around the bottom electrode of the reactor and ions contribute considerably to the deposition, the film develops in a nonuniform VX-765 order manner similar to experimental observations.”
“Background: There is limited evidence to support the recommendation that patients with heart failure (HF) restrict sodium intake. The purpose of this study was to compare differences in cardiac event-free survival between patients with sodium intake above and below 3 g.

Methods: A total of 302 patients

with HF (67% male, 62 +/- 12 years, 54% New York Heart Association [NYHA] Class III/IV, ejection fraction 34 +/- 14%) collected a 24-hour urine sodium (UNa) to indicate sodium intake. Patients were divided into 2 groups using a 3-g UNa cutpoint and stratified by NYHA Class (I/II vs. III/IV). Event-free survival for 12 months was determined by patient or family interviews and medical record review. Differences in cardiac event-free survival were determined by Kaplan-Meier survival curve with log-rank test and Cox hazard regression.

Results: The Cox regression hazard ratio for 24-hour UNa 3 g in NYHA Class I/II was 0.44 (95% confidence interval [CI] = 0.20-0.97) and 2.54 (95% CI = 1.10-5.84) for NYHA III/IV after controlling for age, gender, HF etiology, body mass index, ejection fraction, and total comorbidity score.

To check the utility and accuracy of the method in recognizing measures’ differences, other aims were comparison of two different groups of people and statistical validation.

Study design. The study sample was composed of 100 consecutive patients (56 females and 44 males) undergoing a routine CT scanning. The images, obtained through the reference

plane of the palate, were post-processed on a PC workstation. A goniometer construction was superimposed and centered on the posterior nasal spine, where a grid of eighteen rays was developed to AZD6738 clinical trial calculate the superficial soft tissues’ depths of the face. To test the validity of the method, three of the rays were measured twice, by the same as by another observer. Step-by-step procedures were attained to get maximum standard in measures’ reliability.

Results. Superficial soft tissues’ depths were obtained and sex differences were analyzed (Student’s t and Wilcoxon rank-sum test). The statistical reliability was proven with Bland-Altman statistics and the upper 95% limit of agreement was 1.459 mm for intraobserver repeatability and 1.886 mm for interobserver reproducibility. Validation of the method

was proven by intraclass correlation coefficient (0.99 both for repeatability and reproducibility) and mean differences (respectively 0.6% and 0.4%).

Conclusion. The method appeared easy to be applied, reliable and not observer dependent, so suitable for study single as multiple patients with CT images. Future analyses shall be possible. (Oral Surg Oral Med Oral Alisertib clinical trial Pathol Oral Radiol Endod 2010;110:101-109)”
“Understanding the vascular injury pathway is crucial to developing rational strategies for secondary stroke prevention in children. The multicenter Vascular Effects of Infection in Pediatric Stroke (VIPS) cohort study will test the hypotheses that (1) infection can

lead to childhood arterial ischemic stroke by causing vascular injury and (2) resultant arteriopathy and inflammatory markers predict recurrent stroke. The authors are prospectively enrolling 480 children (aged 1 month through BMS-754807 datasheet 18 years) with arterial ischemic stroke and collecting extensive infectious histories, blood and serum samples (and cerebrospinal fluid, when clinically obtained), and standardized brain and cerebrovascular imaging studies. Laboratory assays include serologies (acute and convalescent) and molecular assays for herpesviruses and levels of inflammatory markers. Participants are followed prospectively for recurrent ischemic events (minimum of 1 year). The analyses will measure association between markers of infection and cerebral arteriopathy and will assess whether cerebral arteriopathy and inflammatory markers predict recurrent stroke.”
“Neonates are known to have a higher risk of cerebral sinovenous thrombosis than children of other age groups.

The levels of epinephrine and norepinephrine increased significantly in DOCA-salt rats and administration of EAFM significantly decreased these parameters to normality. DOCA-salt hypertensive rats exhibited significantly decreased L-arginine and nitrite + nitrate levels and administration of EAFM brought these parameters to normality.

DOA-salt hypertensive rats showed down-regulation of eNOS and up-regulation of ET-1 protein expressions in heart and kidney, and treatment with EAFM prevented down-regulation of eNOS and significantly down-regulated the ET-1 protein expressions. In conclusion, EAFM provides good blood pressure control by enhancing potassium and decreasing sodium levels, decreasing GW4064 purchase levels of epinephrine and norepinephrine, and preventing down-regulation of eNOS and significantly down-regulating ET-1 protein expression.”
“Ludwik Fleck was a

polish physician and bacteriologist with major interest in epistemology. In 1935, he published, in German, a monograph entitled ‘Genesis and development of a scientific fact’. His concepts of ‘thought collective’, ‘thought style’ and ‘active and passive associations’ have been materialized in Banff Dinaciclib classification of renal allograft pathology. The dynamics and evolution of the classification of renal allograft pathology, generated within Banff community, reflect perfectly Fleck’s conceptions. In this essay, the Banff community of thought is characterized as a thought collective, according to Fleck’s epistemology. Since its inception, the classification has been evolving in a continuum of active and passive connections, preserving its initial thought style, based on morphology. Whether the emergence of nonmorphological, molecular techniques will result in the end of morphological thought style is a question

the community is presently facing.”
“Loranthus parasiticus, a Chinese folk medicine, has been widely used for the treatment of brain diseases, particularly in southwest China. BI 10773 ic50 Hence, the present neuroprotection model was designed to investigate its neuroprotective properties against H2O2-induced oxidative stress in NG108-15 cells. L. parasiticus aqueous fraction (LPAF), which was selected in the present study, had proved to be the most active fraction among the other tested extracts and fractions in our previous screening. The restoration of depleted intracellular glutathione (GSH), a major endogenous antioxidant, by LPAF was observed after H2O2 insult. Pretreatment with LPAF substantially reduced the production of intracellular reactive oxygen species generated from H2O2. Apoptotic features such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential were significantly attenuated by LPAF. In addition, cell cycle analysis revealed a prominent decrease in the H2O2-induced sub-G(1) population by LPAF.