The measured parameters were as follows: (1) the s.d. of 12 LV-segment time-to-peak systolic velocities (Ts-SD12), and (2) the maximal difference between peak systolic velocities of any 2 of the 12 segments (Ts-Max). Patients with Ts-SD12 >= 33 ms or Ts-Max >= 100 ms were regarded as having LV systolic dyssynchrony. Patients with systolic dyssynchrony (group 1, n=29) and without systolic dyssynchrony (group 2, n=31) were compared. Among the patients in group 1, antihypertensive treatment significantly

improved LV systolic dyssynchrony (Delta Ts-SD12, -13.1 ms; P<0.001 and Delta Ts-Max, -34.0 ms; P=0.003), whereas it did not demonstrate additional benefit among group 2 patients. The change in LV systolic dyssynchrony was significantly associated with changes in the mean annulus E’ velocity, selleck kinase inhibitor www.selleckchem.com/p38-MAPK.html mean annulus S’ velocity and mean annulus E’/A’ ratio,

but not with changes in blood pressure and LV mass index. It is likely that chronic antihypertensive treatment could reverse the LV systolic dyssynchrony and simultaneously improve subclinical systolic and diastolic function in patients with hypertension and LV systolic dyssynchrony. Hypertension Research (2012) 35, 661-666; doi:10.1038/hr.2012.28; published online 15 March 2012″
“A new exhaust emission inventory of ocean-going vessels (OGVs) was compiled for Hong Kong by using Automatic Identification System (AIS) data for the first time to determine typical main engine load factors, through vessel speed and operation mode characterization. It was found that in 2007, container vessel

was the top emitting vessel type, contributing 9,886, 11,480, 1,173, 521 and 1166 tonnes of SO2, NOx, PM10, VOC and CO, respectively, or about 80%-82% of the emissions. The top five, which also included ocean cruise, oil tanker, conventional cargo vessel and dry bulk carrier, accounted for about 98% of emissions. Emission PD0325901 supplier maps, which add a new spatial dimension to the inventory, show the key emission hot spots in Hong Kong and suggest that a significant portion of emissions were emitted at berth. Scientific evidence about the scale and distribution of ship emissions has contributed in raising public awareness and facilitating stakeholder engagement about the issue. Fair Winds Charter, the world’s first industry-led voluntary emissions reduction initiative, is a perfect example of how careful scientific research can be used in public engagement and policy deliberation to help drive voluntary industry actions and then government proposals to control and regulate marine emissions in Hong Kong and the Pearl River Delta region. (C) 2012 Elsevier Ltd. All rights reserved.”
“Worldwide, paracetamol is administered as a remedy for complaints that occur after vaccination. Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination.

Cardiac angiography was used to display the right ventriculogram (RVG) and the left ventriculogram (LVG). The RVG view was divided into three areas and the LVG view was divided into Vorinostat four areas. Results The paced QRS duration value was significantly longer in the right ventricular apex area compared with the outflow and inflow areas

(160 +/- 15ms vs 140 +/- 15ms, P = 0.02, and vs 133 +/- 17ms, P < 0.001, respectively), but those values were not statistically significantly different between the right ventricular outflow and the right ventricular inflow areas (140 +/- 15ms vs 133 +/- 17ms, P = 0.187). When assessed with LVG views, there were the statistically significant differences in the paced QRS duration values in all areas except the apex area. (LV mid-anterior: AZD7762 concentration 147 +/- 11ms vs LV base: 127 +/- 13ms, P < 0.001, and vs LV mid-septum: 129 +/-

12ms, P = 0.001, respectively.) Conclusions Cardiac angiography showed that there was a relationship between the anatomical right ventricular pacing site and paced QRS duration. Cardiac angiography can help determine the areas that produce shorter paced QRS duration.”
“Purpose of review\n\nThe present review will focus on the role of conventional disease-modifying antirheumatic drugs (DMARDs) in the current management of rheumatoid arthritis (RA).\n\nRecent findings\n\nOver the past several decades, the treatment of RA has been revolutionized, not only by the development of

highly effective biologic Vactosertib manufacturer agents but also through a better understanding of the critical importance of early DMARD treatment with a goal of remission or low disease activity and of how to effectively and safely use conventional DMARDs, either as monotherapy or in combinations.\n\nSummary\n\nConventional DMARDs have proven efficacy in the management of RA and remain a valid treatment option, either in monotherapy or as a component of combination regimens. Although conventional DMARDs have associated toxicities, these are distinct from those of the biologic DMARDs. In addition, conventional DMARDs are much less expensive than biologic DMARDs, and in many cases can be successful in achieving similar control of disease activity. The goal for all patients should be achieving remission, or at least low disease activity, with the most cost-effective therapy possible.”
“Amid growing concern about childhood obesity, the United States spends billions of dollars on food assistance: providing meals and subsidizing food purchases. We examine the relationship between food assistance and body mass index (BMI) for young, low-income children, who are a primary target population for federal food programs and for efforts to prevent childhood obesity. Our findings indicate that food assistance may unintentionally contribute to the childhood obesity problem in cities with high food prices.

IMRT plans generated with the 160-MLC were found to significantly reduce the total delivered monitor units by up to 14.7% and the number of segments by as much as 10.7% compared to the 58-MLC. The average delivery time for the direct aperture optimized (DAO) IMRT plans generated with the 160-MLC Selleckchem Tariquidar was approximately 5 minutes. Overall, compared to the 58-MLC, the new 160-MLC was found to improve dosimetric

conformity and IMRT delivery efficiency.”
“Foot-and-mouth disease, the most devastating and highly contagious viral disease of cloven-footed animals, causes significant financial losses either due to deaths of young animals, loss of milk, meat and drastic fall in productive performances or serious limitations on development of livestock industry due to restrictions on international trade. In spite of the considerable information accumulated in the last years on the disease, it still affects extensive areas of the world and ranks as first in the list ‘A’ of infectious diseases of animals according to the Office International des Epizooties, Perris, France. In this review, we have to summarize the state of knowledge in basic and applied areas of FMD research with emphasis on epidemiology and diagnosis to make progress in controlling the disease

from the livestock.”
“Low-contrast images, such as color microscopic images of unstained histological specimens, are composed of objects with highly correlated spectral profiles. Such images are very hard to segment. Here, we present a method that nonlinearly maps low-contrast color image into an image with an increased number of non-physical channels and a decreased https://www.selleckchem.com/products/ve-821.html correlation between spectral profiles. The method is a proof-of-concept validated on the unsupervised segmentation of color images of unstained

specimens, in which case the tissue components appear colorless when viewed under the light microscope. Specimens of human hepatocellular carcinoma, human liver with metastasis from colon and gastric cancer and mouse fatty liver were used for validation. The average correlation between the spectral profiles of the tissue components was greater than 0.9985, and the worst case correlation was greater than 0.9997. The proposed method can potentially PD173074 be applied to the segmentation of low-contrast multichannel images with high spatial resolution that arise in other imaging modalities.”
“We have investigated the impacts of 63 different low-molecular-weight compounds, most of them plant derived, on the in vitro expression of two antifungal biosynthetic genes by the plant-protecting rhizobacterium Pseudomonas fluorescens CHA0. The majority of the compounds tested affected the expression of one or both antifungal genes. This suggests that biocontrol activity in plant-beneficial pseudomonads is modulated by plant-bacterium signaling.”
“Myxococcus fulvus HW-1, a salt-tolerant bacterial strain, which was isolated from a coastal environment, changes its behavior with different salinities.

05) in an independent Dutch cohort (Leiden Longevity Study n = 599). Although the four genes have previously been associated with skin color variation and skin cancer risk, all association AZD6244 signals remained highly significant (P smaller than 2 x 10(-8)) when conditioning the association analyses on skin color. We conclude that genetic variations in IRF4, MC1R, RALY/ASIP, and BNC2 contribute to the acquired amount of facial pigmented spots during aging, through pathways independent of the basal melanin production.”
“Cerebral deposition of beta-amyloid (A beta)peptides

is a pathological hallmark of Alzheimer disease. Intramembranous proteolysis of amyloid precursor protein by a multiprotein gamma-secretase complex generates A beta. Previously, it was reported that CD147,

a glycoprotein that stimulates production of matrix metalloproteinases (MMPs), click here is a subunit of gamma-secretase and that the levels of secreted A beta inversely correlate with CD147 expression. Here, we show that the levels and localization of CD147 in fibroblasts, as well as postnatal expression and distribution in brain, are distinct from those of integral gamma-secretase subunits. Notably, we show that although depletion of CD147 increased extracellular A beta levels in intact cells, membranes isolated from CD147-depleted cells failed to elevate A beta production in an in vitro gamma-secretase assay. Consistent with an extracellular source that modulates A beta metabolism, synthetic A beta was degraded more rapidly in the conditioned medium of cells overexpressing CD147. Moreover, modulation of CD147 expression had no effect on epsilon-site cleavage of amyloid precursor protein and Notch1 receptor. Collectively, our results demonstrate that CD147 modulates A beta levels not by regulating gamma-secretase activity, but by stimulating extracellular degradation of A beta. In view of the known function of CD147 in MMP production, we postulate that CD147 expression influences A beta levels by an indirect mechanism involving MMPs that can degrade extracellular A beta.”
“Depression in childhood or

check details adolescence is associated with increased rates of depression in adulthood. Does this justify efforts to detect (and treat) those with symptoms of depression in early childhood or adolescence? The aim of this study was to determine how well symptoms of anxiety/depression (A-D) in early childhood and adolescence predict adult mental health. The study sample is taken from a population-based prospective birth cohort study. Of the 8556 mothers initially approached to participate 8458 agreed, of whom 7223 mothers gave birth to a live singleton baby. Children were screened using modified Child Behaviour Checklist (CBCL) scales for internalizing and total problems (T-P) at age 5 and the CBCL and Youth Self Report (YSR) A-D subscale and T-P scale at age 14. At age 21, a sub-sample of 2563 young adults in this cohort were administered the CIDI-Auto.

Moreover, it might lead to increased adrenergic descending inhibition associated with increased sympathetic modulation. Thus, pain research might be able to alter Liproxstatin-1 nmr our view on autonomic regulation, which is putatively associated with increased cardiac mortality of the disease.”
“Women who were

themselves small-for-gestational age (SGA) are at a greater risk of adulthood diseases such as non-insulin-dependent diabetes mellitus (NIDDM), and twice at risk of having an SGA baby themselves. The aim of this study was to examine the intergenerational pig. Low (L) and normal (N) birth weight female piglets were followed throughout their first pregnancy (generation 1 (0)). After they had given birth, the growth and development of the lightest (I) and heaviest (n) female piglet from each litter were monitored until approximately 5 months of age (generation 2 (G2)). A glucose tolerance test (GTT) was conducted on G1 pig at similar to 6 months of age and again during late pregnancy; a GTT was also conducted on G2 pigs at similar to 4 months of age. G1 L offspring exhibited impaired glucose metabolism in later life compared to their G1 N sibling but in the next generation a similar scenario was only observed between I and n offspring born to G1 L mothers. Despite G1

L mothers showing greater glucose intolerance in late pregnancy and a decreased litter size, average piglet birth weight was reduced and there was also a large variation in https://www.selleckchem.com/products/Flavopiridol.html litter weight; this suggests that they were, to some extent, prioritising their nutrient intake towards themselves rather than

promoting their reproductive performance. There were Navitoclax numerous relationships between body shape at birth and glucose curve characteristics in later life, which can, to some extent, be used to predict neonatal outcome. In conclusion, intergenerational effects are partly seen in the pig. It is likely that some of the intergenerational influences may be masked due to the pig being a litter-bearing species.”
“During standing balance, kinematics of postural behaviors have been previously observed to change across visual conditions, perturbation amplitudes, or perturbation frequencies. However, experimental limitations only allowed for independent investigation of such parameters. Here, we adapted a pseudorandom ternary sequence (PRTS) perturbation previously used in rotational support-surface perturbations (Peterka in J Neurophysiol 88(3):1097-1118, 2002) to a translational paradigm, allowing us to concurrently examine the effects of vision, perturbation amplitude, and frequency on balance control. Additionally, the unpredictable PRTS perturbation eliminated effects of feedforward adaptations typical of responses to sinusoidal stimuli. The PRTS perturbation contained a wide spectral bandwidth (0.08-3.67 Hz) and was scaled to 4 different peak-to-peak amplitudes (3-24 cm).

Applications learn more were designed modularly and can be used standalone. These tools are written in Perl and Python programming languages and are supported on Windows platforms. They are all released under an Open Source Software license and can be freely downloaded from our software repository hosted at GoogleCode.”
“In this work, we report that Entpd1(-/-) mice, deficient for the ectonucleotidase nucleoside triphosphate

diphosphohydrolase-1 (NTPDase1), produce smaller litters (27% reduction) compared with wild-type C57BL6 animals. This deficit is linked to reduced in vivo oocyte fertilization by Entpd1(-/-) males (61 +/- 11% versus 88 +/- 7% for Entpd1(-/-)). Normal epididymal sperm count, spermatozoa morphology, capacitation, and motility and reduced ejaculated sperm number (2.4 +/- 0.5 versus 3.7 +/- 0.4 million for Entpd1(-/-)) pointed to vas deferens dysfunction.

NTPDase1 was localized by immunofluorescence in the tunica muscularis of the vas deferens. Its absence resulted in a major ATP hydrolysis deficiency, as observed in situ by histochemistry and in primary smooth muscle cell cultures. In vitro, Entpd1(-/-) vas deferens displayed an exacerbated contraction to ATP, a diminished response to its non-hydrolysable analog alpha beta MeATP, and a reduced contraction to electrical field stimulation, suggesting altered P2X1 receptor function with a propensity to desensitize. This functional alteration was accompanied by a 3-fold decrease in P2X1 protein expression in Entpd1(-/-) vas deferens with no click here variation in mRNA levels. Accordingly, exogenous nucleotidase activity was required

LDN-193189 datasheet to fully preserve P2X1 receptor activation by ATP in vitro. Our study demonstrates that NTPDase1 is required to maintain normal P2X1 receptor functionality in the vas deferens and that its absence leads to impaired peristalsis, reduced spermatozoa concentration in the semen, and, eventually, reduced fertility. This suggests that alteration of NTPDase1 activity affects ejaculation efficacy and male fertility. This work may contribute to unveil a cause of infertility and open new therapeutic potentials.”
“Affecting more than 230,000,000 patients, diabetes mellitus is one of the most frequent metabolic disorders in developed countries. Among other complications, diabetic patients have an increased fracture risk and show delayed fracture healing. During the disease progression, these patients’ blood glucose and insulin levels vary significantly. Thus, the aim of this study was to analyze the effects of glucose and insulin on primary human osteoblasts. Although, in the presence of insulin and glucose, proliferation of osteoblasts was increased (1.2- to 1.7-fold), their alkaline phosphatase activity and, consequently, production of mineralized matrix were significantly reduced down to 55 % as compared to control cells (p < 0.001).

).

Using an image-guided probe over the skin surface, we navigated the dorsal fusion mass to identify a thin area at the L4-L5 level. A small incision was made and the image-guided probe was used to target the selected thin area and drill an adequate opening in the fusion mass. We inserted a Tuohy needle through the bony defect for passage of the intrathecal catheter. We confirmed adequate catheter placement using free flowing cerebrospinal fluid and fluoroscopy. The remainder of the IDDS implant proceeded per routine. Results: The patient tolerated the procedure well and had no complications. The morphine IDDS improved his overall pain and function with minimal Emricasan research buy side effects. Conclusions: This is the first case report

using 3D cone beam computed tomography-based image selleck compound guidance for the placement of an intrathecal catheter through a bony fusion mass. This technique appears to be a viable option for IDDS implantation in patients with difficult anatomy.”
“Aim: Congenital cytomegalovirus (CMV) infection can cause a variety of neurological deficits of delayed onset in infants who are asymptomatic at birth. The aim of this study was to investigate the prevalence of congenital CMV infection among children with autism spectrum disorder (ASD) in Nagasaki, Japan. Methods: Twenty-nine children with ASD who were born in Nagasaki and had no other major neurological deficits were recruited. Two of the patients were excluded due to significant perinatal events. The remaining 27 children were investigated retrospectively for congenital CMV infection by analyzing dried blood spot samples

or dried umbilical cords for CMV DNA using real-time PCR. Results: CMV DNA was detected in two (7.4%) of the 27 children. Neither of the patients had perinatal histories suggestive of congenital CMV disease or other neurological deficits, including hearing impairment and epilepsy. The severity of their autistic disorders varied considerably. Conclusions: The rate of congenital CMV infection in this study (two of 27 children with ASD), which was significantly (p = 0.004) higher than the incidence of congenital CMV infection in Nagasaki (0.31%, 10/3230 live births), suggests the involvement of congenital CMV infection in a portion of check details children with ASD, although definite diagnosis was not obtained due to limited clinical data of the study subjects. (C) 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.”
“In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption.

Mean BCVA improved from 20/340 (logarithm of the minimal angle of resolution [logMAR] 1.23) to 20/129 (0.81) within 3 months of surgery, P < .0001. Eyes with a preoperative vision of 20/40 to 20/200 (47 eyes) improved from a mean of 20/81 (logMAR 0.61) preoperatively to 20/43

(0.33), P < .0001, postoperatively. Posterior capsule pacification Selleck LY3039478 occurred in 66 eyes (82.5%), and 42 eyes (52.5%) underwent a YAG laser capsulotomy at a mean of 10.8 months after surgery. Fifteen eyes (18.8%) of 10 patients (21.3%) had signs of phacodonesis (3 eyes noted preoperatively, 8 intraoperatively, and 4 postoperatively). One patient had bilateral dislocated in-the-bag intraocular lenses at 5.5 years and 6 years after surgery.\n\nCONCLUSION: Cataract surgery yields significantly improved Snellen visual acuity in a majority of RP patients with a preoperative vision of 20/200 or better. Conversely, patients with a preoperative visual acuity of 20/400 or worse generally

have more limited objective improvements, likely because of AZD8186 in vivo macular involvement, but usually report noticeable subjective improvement. A high prevalence of zonular instability is seen in RP patients undergoing cataract extraction. It is therefore important to conduct a careful preoperative assessment of lens stability with preparation for adjunctive methods that augment intraoperative and postoperative lens stabilization. (C) 2013 by Elsevier Inc. All rights reserved.”
“Background/Aims: Melatonin receptor 1A (MTNR1A) gene is a regulator

of circadian rhythms and reproductive processes. CRT0066101 The MTNR1A gene is also a potential candidate gene of polycystic ovary syndrome (PCOS). The aim of the present study was to determine whether or not the MTNR1A gene polymorphism is associated with a predisposition to PCOS. Methods: The single nucleotide polymorphism (SNP) rs2119882 in the MTNR1A gene was detected in 482 patients with PCOS and 522 healthy Chinese Han women. Subsequently, the association of MTNR1A gene variants with plasma glucose, insulin levels during oral glucose tolerance tests (OGTTs) and hormone levels was investigated. Results: The frequencies of genotypes and allelotypes of SNP rs2119882 differed significantly between PCOS cases and healthy controls (p < 0.001 and p = 0.002, respectively). SNP rs2119882 was associated with higher fasting plasma glucose concentrations (p = 0.021) and OGTT-induced insulin release at 0, 30, 60, and 120 min (all p < 0.05) in PCOS cases, as well as an increased homeostasis model assessment for insulin resistance (p = 0.005). Conclusion: SNP rs2119882 is associated with PCOS. Copyright (C) 2011 S. Karger AG, Basel”
“Thiazolidinediones (TZD), a class of anti-diabetic drugs, determine bone loss and increase fractures particularly in post-menopausal women, thus suggesting a protective role of sex steroids.

We found that human IgGs are stable with minimal heat-induced degradation and aggregation at pH 5.0-5.5 irrespective of their subclass. We also found that IgG1 is more susceptible to fragmentation, whereas IgG4 is more susceptible to aggregation. This basic information emphasizing the influence of pH on IgG stability

should facilitate the optimization Nutlin-3 of formulation conditions tailored to individual antibodies for specific uses.”
“Background: It was of interest to investigate the factors affecting kinetics of transformation of fluconazole polymorph II (the metastable form) to fluconazole polymorph I (the stable form) using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Method: Fluconazole polymorphs I and II both were prepared by crystallization in dichloromethane. The two forms were characterized using differential scanning calorimetry, thermogravimetric

analysis, powder X-ray diffraction, solubility, and DRIFTS. Transformation of polymorph II to polymorph I was also studied under different isothermal temperatures using DRIFTS. Kinetic analyses of the data were done using model-dependent and model-independent methods. Eighteen solid-state reaction models were used to interpret the experimental results. Results: Based on statistics, the Prout-Tompkins model provided the best fit for the transformation. The activation energy (Ea) value derived from the rate constants of the Prout-Tompkins model was 329 kJ/mol. Model-independent MK-2206 cell line Nocodazole inhibitor analysis was also

applied to the experimental results. The average values calculated using both methods were not significantly different. Factors affecting kinetics of transformation such as mechanical factors, relative humidity, and the effect of seeding were also studied. Mechanical factors, which included trituration and compression, proved to enhance transformation rate significantly. Relative humidity proved to transform both polymorphs to monohydrate form. The presence of seed crystals of polymorph I was proved not to affect the transformation process of polymorph II to polymorph I. Effect of solvent of crystallization (dichloromethane) was studied. A significant change of the rate of transformation was proved in the presence of solvent vapors, and a change on the mechanism was proposed.”
“Background. In accord with the cancer stem cell (CSC) theory, only a small subset of cancer cells are capable of forming tumors. We previously reported that CD44 isolates tumorigenic cells from head and neck squamous cell cancer (HNSCC). Recent studies indicate that aldehyde dehydrogenase (ALDH) activity may represent a more specific marker of CSCs.\n\nMethods. Six primary HNSCCs were collected. Cells with high and low ALDH activity (ALDH(high)/ALDH(low)) were isolated. ALDH(high) and ALDH(low) populations were implanted into NOD/SCID mice and monitored for tumor development.\n\nResults.

We analyze the results from Brownian dynamics simulations using the framework of diffusion-limited cluster aggregation. www.selleckchem.com/products/hmpl-504-azd6094-volitinib.html When entanglements prevail, which is true in the absence of N17, small spherical clusters and large linear aggregates form on distinct timescales, in accord with in vitro experiments. Conversely, when entanglements are quenched and a barrier to intermolecular associations is introduced, both of which are attributable to N17, the timescales for forming small species and large linear aggregates become similar. Therefore,

the combination of a reduction of interchain entanglements through homopolymeric polyQ and barriers to intermolecular associations appears to be sufficient for providing a minimalist phenomenological rationalization of in vitro observations regarding the effects of N17 on polyQ aggregation.”
“dDsk2 is a conserved extraproteasomal ubiquitin receptor that targets ubiquitylated proteins for degradation. Here we report that dDsk2 plays a nonproteolytic function in transcription regulation. dDsk2 interacts with the dHP1c complex, localizes at promoters of developmental genes and is required for transcription. Through the ubiquitin-binding Pexidartinib domain, dDsk2 interacts with H2Bub1, a modification that occurs at dHP1c complex-binding sites. H2Bub1 is not required for binding of the complex; however, dDsk2

depletion strongly reduces H2Bub1. Co-depletion of the H2Bub1 deubiquitylase dUbp8/Nonstop suppresses this reduction Ricolinostat supplier and rescues expression of

target genes. RNA polymerase II is strongly paused at promoters of dHP1c complex target genes and dDsk2 depletion disrupts pausing. Altogether, these results suggest that dDsk2 prevents dUbp8/Nonstop-dependent H2Bub1 deubiquitylation at promoters of dHP1c complex target genes and regulates RNA polymerase II pausing. These results expand the catalogue of nonproteolytic functions of ubiquitin receptors to the epigenetic regulation of chromatin modifications.”
“Recent genome wide association studies have identified CLU, CR1, ABCA7 BIN1, PICALM and MS4A6A/MS4A6E in addition to the long established APOE, as loci for Alzheimer’s disease. We have systematically examined each of these loci to assess whether common coding variability contributes to the risk of disease. We have also assessed the regional expression of all the genes in the brain and whether there is evidence of an eQTL explaining the risk. In agreement with other studies we find that coding variability may explain the ABCA7 association, but common coding variability does not explain any of the other loci. We were not able to show that any of the loci had eQTLs within the power of this study. Furthermore the regional expression of each of the loci did not match the pattern of brain regional distribution in Alzheimer pathology.