Turkish versions of CFQ-R Child and

Parent instruments ha

Turkish versions of CFQ-R Child and

Parent instruments have demonstrated adequate reliability and validity and can be utilized in clinical trials or integrated into clinical evaluation and follow-up of Turkish children with CF.”
“Purpose: Clinical and preclinical data VX-770 concentration show a wide variability of tumour response to combined inhibition of the Epidermal Growth Factor Receptor (EGFR) and radiotherapy or chemotherapy. Differences are obvious not only between different tumour entities, but also between different combination schedules and different classes of drugs. The underlying reasons are currently not well understood.

Conclusions: In light of the disappointing results of some phase III trials on combined EGFR tyrosine kinase (TK) inhibition

and chemotherapy click here in non-small-cell lung cancer, but also of some early clinical trials on the triple combination of EGFR inhibitors and radio-chemotherapy, negative interactions between the components of the treatment cannot be ruled out. Also, there is increasing evidence for a differential activity of anti-EGFR antibodies and EGFR-TK inhibitors. Potential reasons are an immunogenic component of the cytotoxic effect of chimeric antibodies, alternative signal transduction pathways leading to acquired resistance against the drugs, different effects on tumour micromilieu or nutritional supply, differences

in pharmacokinetics and intratumoural distribution or different effects on cancer stem cells. Clarifying these potential mechanisms will require further preclinical and clinical research effort but could in future enable us to individually tailor the use of molecular targeted drugs in order to fully utilise their high potential in cancer therapy.”
“It is unknown whether the glycosaminoglycan drug sulodexide interferes with transforming growth factor-beta 1-a member of heparin-binding family and a potent regulator of human biology and diseases. Hence, a 2-week pilot Study was performed in 11 healthy men. Sulodexide was initially administered intravenously selleck chemicals in a single dose, then-orally for 12 days and-again intravenously on study completion. Initial injection had no effect on activated from of the growth factor measured in plasma after 10 and 120 min; no change was also observed after 120 min from drug ingestion On day 7. On final intravenous administration, the growth factor levels increased by almost 60% after 10 min and remained elevated; the 120-min levels directly correlated with sulodexide dosage. Baseline cytokine levels decreased during the 2-week trial by more than 50%. In conclusion, transforming growth factor-beta 1 release and likely downregulation of its expression may constitute novel pharmacological effects of sulodexide.

The authors have indicated no significant interest with commercia

The authors have indicated no significant interest with commercial supporters.”
“We have carried out an experimental study to reveal the dielectric function of SmH(x)(x=2.28,2.42,2.56,2.57) WH-4-023 cost films based on room-temperature reflectivity

for photon energies ranging from 0.05 to 6.5 eV. The derivation of the dielectric functions has been carried out using model dielectric functions as well as Kramers-Kronig analysis. It is inferred from our analysis that when the H/Sm value is increased from 2.28 to 2.57, (i) the interband transition band located in the ultraviolet region shows a redshift of about 1 eV, (ii) the relatively weak transition band located in the near-infrared region shows a reduction in intensity, and (iii) the unperturbed plasma frequency of free carriers decreases slightly. The behaviors (i), (ii), and (iii) caused by the H/Sm selleck chemical value change are thoroughly approximately the same as those observed for YH(x), suggesting that these trends are characteristic of H-M systems showing a metal-insulator transition. It was also confirmed from our structural analysis that these changes

in the dielectric function are achieved without a change in the lattice constant. The origin of this constancy in the lattice constant in our samples with different H/Sm values is discussed by assessing the T- and O-site hydrogen concentrations. The hydrogen incorporation effect is also observed in the magnitude of the unperturbed plasma frequency, about 1.7 eV, which is unexpectedly small compared to conventional metals. This characteristic can possibly be attributed to mass enhancement of mobile carriers; we obtained VX-661 nmr an effective mass of about 10m(0)

(where m(0) is the free electron mass) when the carrier density estimated from the Hall coefficient value is used.”
“The ingestion toxicity of three Lamiaceae essential oils (EOs) – Hyptis suaveolens, Rosmarinus officinalis and Lavandula angustifolia – incorporated in protein baits was evaluated against Bactrocera oleae, a worldwide pest of olive fruits. In laboratory conditions, all the tested EOs showed dose-dependent toxicity on B. oleae, with mortality rates ranging from 12% (EO concentration: 0.01% w:v) to 100% (EO concentration: 1.75% w:v). Semi-field results highlighted the toxicity of L. angustifolia and H. suaveolens EOs, which exerted more than 60% of flies mortality at a concentration of 1.75% (w:v). Gas Chromatography-Electron Impact Mass Spectrometry analyses of the three EOs showed that H. suaveolens EO was dominated by monoterpene and sesquiterpene hydrocarbons. Oxygenated monoterpenes were the main chemical class in R. officinalis and L. angustifolia EOs. Further research is needed to evaluate the efficacy of these EOs plus food bait against the olive fruit fly in the open field.”
“BACKGROUND Periorbital hyperpigmentation (POH) presents with a dark area surrounding the eyelids.

This review aims to enunciate the principles of organ perfusion a

This review aims to enunciate the principles of organ perfusion and preservation as they relate to indication, aspects of organ protection and to highlight future developments.”
“Objective-To determine the effects of body position and extension of the neck and extremities on CT measurements of ventilated lung volume in red-eared slider turtles (Trachemys scripta elegans).

Design-Prospective crossover-design study.

Animals-14 adult

red-eared slider turtles.

Procedures-CT was performed on turtles in horizontal ventral recumbent and vertical left lateral recumbent, right lateral recumbent, and caudal recumbent body positions. In sedated turtles, evaluations were performed SB203580 in horizontal ventral recumbent body position with and without extension of the neck

and extremities. Lung volumes were estimated from helical CT images with commercial software. Effects of body position, extremity and neck extension, sedation, body weight, and sex on lung volume were analyzed.

Results-Mean +/- SD volume of dependent lung tissue was significantly decreased in vertical Selleckchem SNX-5422 left lateral (18.97 +/- 14.65 mL), right lateral (24.59 +/- 19.16 mL), and caudal (9.23 +/- 12.13 mL) recumbent positions, compared with the same region for turtles in horizontal ventral recumbency (48.52 +/- 20.08 mL, 50.66 +/- 18.08 mL, and 31.95 +/- 15.69 mL, respectively). Total lung volume did not differ among positions because of compensatory increases in nondependent lung tissue. Extension of the extremities and neck significantly increased total lung volume (12794 +/- 35.53 mL), compared with that in turtles with the head, neck, and extremities withdrawn into the shell (103.24 +/- 40.13 mL).

Conclusions and Clinical Relevance-Vertical positioning of red-eared

sliders significantly affected lung volumes and could potentially affect interpretation of radiographs obtained see more in these positions. Extension of the extremities and neck resulted in the greatest total lung volume.”
“We propose that counterfactual representations for reasoning about the past or predicting the future depend on structured event complexes (SECs) in the human prefrontal cortex (PFC; ‘What would happen if X were performed in the past or enacted in the future?’). We identify three major categories of counterfactual thought (concerning action versus inaction, the self versus other and upward versus downward thinking) and propose that each form of inference recruits SEC representations in distinct regions of the medial PFC. We develop a process model of the regulatory functions these representations serve and draw conclusions about the importance of SECs for explaining the past and predicting the future.”
“The magnetic dead layer (MDL) in amorphous CoFeB layers is investigated for four different unit structures.

Our study, therefore, provides new therapeutic avenues that could

Our study, therefore, provides new therapeutic avenues that could help to prevent the putative pro-amyloidogenic properties of small volatile anesthetics.”
“A recent study of two widely used angiotensin receptor blockers reported a reduced risk of cardiovascular events (-14.4%) when using candesartan compared with losartan in the primary treatment of hypertension. In addition to clinical benefits, costs associated with treatment strategies must be considered when allocating scarce health-care resources. The aim of this study was to assess resource use and costs of losartan and candesartan in hypertensive patients. Resource use (drugs, outpatient contacts, hospitalizations and laboratory

tests) associated www.selleckchem.com/products/epz015666.html with losartan and candesartan treatment was estimated in 14 100 patients in a real-life clinical

setting. We electronically extracted patient data from primary care records Torin 2 order and mandatory Swedish national registers for death and hospitalization. Patients treated with losartan had more outpatient contacts (+15.6%), laboratory tests (+13.8%) and hospitalizations (+13.8%) compared with the candesartan group. During a maximum observation time of 9 years, the mean total costs per patient were 10 369 Swedish kronor (95% confidence interval: 3109-17 629) higher in the losartan group. In conclusion, prescribing candesartan for the primary treatment of hypertension results in lower long-term health-care costs compared with losartan. Journal of Human Hypertension (2011) 25, 130-136; doi: 10.1038/jhh.2010.36; published online 8 April 2010″
“On 12 May 2008, an earthquake measuring 8.0 on the Richter scale struck Wenchuan County, Sichuan, China. Between 12 May and 11 June, 1823 victims were hospitalized in West China Hospital. These patients were severely injured, and INCB028050 molecular weight most

of their wounds were contaminated. Here, the results of bacteriological identification and antibiotic susceptibility testing of 725 non-duplicate isolates from earthquake victims are presented. Gram-negative bacilli were most frequently isolated (71.3%). Only 18.9% of isolates were Gram-positive bacteria; Candida spp. accounted for 9.7%, and Gram-negative cocci for 0.1%. After anaerobic culture, four Clostridium sordellii strains and one Clostridium bifermentans strain were isolated from deep wounds. Specimen culture from earthquake victims revealed a spectrum of pathogens and antibiotic susceptibilities that was different from that usually encountered in West China Hospital, especially concerning methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producers, and multidrug-resistant (MDR) non-fermenting Gram-negative bacilli. The pathophysiology of the injuries in earthquake victims was different from that in the patients who were not earthquake victims.

We evaluated immunohistochemical expressions of cyclin D1, CDK4 a

We evaluated immunohistochemical expressions of cyclin D1, CDK4 and phosphorylated pRb (p-pRb) in 50 PAs to investigate a role for functional inactivation of pRb associated with cyclin D1/CDK4 overexpression in pituitary tumorigenesis

and to correlate it with clinicopathologic variables. Methods : Fifty human PAs were immunohistochemically stained for cyclin D1, CDK4 and p-pRb (Thr 356). Correlations between their expression and the clinicopathologic characteristics were statistically analyzed. Results: Cyclin Selleckchem GDC941 D1 and CDK4 were overexpressed in 56% and 64%, respectively; pRb was hyperphosphorylated in 64%. Forty one cases (82%) showed one or more of these altered expressions. Overexpressions of cyclin D1 and CDK4 were correlated with functional pRb inactivation. Cyclin D1 overexpression was associated with apoplexy and growth hormone production. Conclusions : Functional inactivation of pRb associated with the cyclin D1/CDK4 overexpression might play a key role in human pituitary tumorigenesis. CDK4 worked in concert with cyclin D1 to hyperphosphorylate pRb. Pituitary apoplexy appeared to be associated

with cyclin D1 overexpression.”
“Background: There is no consensus on the optimum imaging method to use to confirm the diagnosis of true CCI-779 scaphoid fractures among patients with suspected scaphoid fractures. This study tested the null hypothesis that computed tomography (CT) and magnetic resonance imaging (MRI) have the same diagnostic performance characteristics for the diagnosis of scaphoid fractures.

Methods: Thirty-four consecutive patients with a suspected scaphoid fracture (tenderness of the scaphoid and normal radiographic findings after a fall on the outstretched hand) underwent CT and MRI within ten days after a wrist injury. The reference standard for a true fracture of the scaphoid was six-week follow-up radiographs in four views. A panel including surgeons and radiologists came to a consensus diagnosis for each type of imaging. The images were considered in a randomly ordered, blinded fashion,

independent of the other types of imaging. We calculated sensitivity, specificity, and accuracy as well as positive and negative predictive values.

Results: The reference standard revealed six true fractures of the scaphoid (prevalence, 18%). CT demonstrated a fracture in five patients (15%), with one false-positive, Sapitinib research buy two false-negative, and four true-positive results. MRI demonstrated a fracture in,seven patients (21%), with three false-positive, two false-negative, and four true-positive results. The sensitivity, specificity, and accuracy were 67%, 96%, and 91%, respectively, for CT and 67%, 89%, and 85%, respectively, for MRI. According to the McNemar test for paired binary data, these differences were not significant. The positive predictive value with use of the Bayes formula was 0.76 for CT and 0.54 for MRI. The negative predictive value was 0.94 for CT and 0.


“Purpose of study To describe a simple and reliable method


“Purpose of study To describe a simple and reliable method of intra-operative localisation of thoracic spine in a single surgical setting.

Summary of background Intra-operative localisation of thoracic spine levels can be difficult due to anatomical constraints, such as scapular shadow, patient’s size and poor bone quality. This is particularly true in cases of thoracic discectomies in which the vertebral bodies appear normal. There are several methods described in recent literature to address this. Many of them require a separate procedure which was performed often the previous day. We report a technique which addresses the issue

of localising thoracic level intra-operatively.

Materials and methods After induction of general anaesthesia, selleck compound the patient was placed prone and the pedicle of interest was identified using fluoroscopy. A K-wire was then inserted percutaneously

into this pedicle under image guidance [confirmed in the antero-posterior (AP) and lateral views]. The wire was then cut close to the skin after bending it. The patient was now positioned laterally and the intended procedure performed through an anterior trans-thoracic approach. The ‘K’ wire PLX4032 order was removed at the end of the procedure.

Results and conclusion We routinely used this technique in all our thoracic discectomies (four cases in 2 years). There were no intra-operative complications. This method is simple, avoids the patient undergoing two procedures and requires no more ability than placing an implant in the pedicle under fluoroscopy. Placing the ‘K’ wire into a fixed point like the pedicle facilitates rapid intra-operative viewing of the level of interest and is removed easily at the conclusion of surgery.”
“Argatroban was used as the anticoagulant during cardiopulmonary bypass (CPB) in a patient with heparin-induced thrombocytopenia (HIT) type II undergoing mitral valve replacement. Dosage was reduced

because of preoperative congestive liver disorder. Perioperative coagulability was poor, and, ultimately, failure of hemostasis led to a fatal outcome. Although argatroban use as an anticoagulant for HIT is reported, the optimal dose has not been established. During IWR-1-endo long-term CPB, increasing the total dosage may extend anticoagulant ability, leading to dose dependence. Because no antagonist for argatroban”
“Since 1988, the American Society for Clinical Pathology (ASCP) has conducted surveys to determine the extent and distribution of workforce shortages within the nation’s clinical laboratories. This confidential survey has been administered every 2 years and has served as a source of information for academic, government, and industry labor analysts. Results from past surveys show that laboratory medicine is a rapidly evolving field.

Considerable insight into the biology and drug resistance of the

Considerable insight into the biology and drug resistance of the leprosy bacillus has been obtained from genomics. M. leprae has undergone reductive evolution and pseudogenes now occupy half of its genome. Comparative genomics of four different strains revealed remarkable conservation of the genome (99.995% identity) yet uncovered 215 polymorphic sites, mainly single nucleotide polymorphisms, and a handful of new pseudogenes. Mapping

these polymorphisms in a large panel of strains defined 16 single nucleotide polymorphism-subtypes that showed strong geographical associations and helped retrace the evolution of M. leprae.”
“Study Design. A gross anatomic and magnetic resonance imaging study of intervertebral disc (IVD) degeneration in fresh cadaveric

lumbar spines.

Objective. Quisinostat supplier The purpose of this study was to find the rate of IVD degeneration.

Summary of Background Data. Age, sex, race, and lumbar level are among some of the factors that play a role in IVD degeneration. The rate at which IVDs degenerate is unknown.

Methods. Complete lumbar spine segments (T11/T12 to S1) were received within 24 hours of death. The nucleus pulposus, anulus fibrosus, cartilaginous and bony endplate, and the peripheral vertebral Tubastatin A body were assessed with magnetic resonance imaging and IVD degeneration was graded by two observers from grade 1 (nondegenerated) to grade 5 (severely degenerated) on the basis of a scale developed by Tanaka et al. The specimens were then sectioned and gross anatomic evaluation was performed according to Thompson et al.

Results. A total of 433 donors and 1712 CRT0066101 nmr IVDs were analyzed. There were 366 whites, 47 Africans, 16 Hispanics, 4 Asian. There were 306 male and 127 female donors. The age range was 14 to 81 years, (average: 60.5 +/- 11.3). For donors greater than age 40, the L5/S1 IVD degenerated at a significantly faster rate of 0.043 per year compared to 0.031, 0.034, 0.033, 0.027 for L1/L2, L2/L3, L3/L4, L4/L5, respectively. For donors younger than 40, L5/S1 IVD degenerated at a significantly faster rate of 0.141/y

compared to 0.033, 0.021, 0.031, 0.050 for L1/L2, L2/L3, L3/L4, L4/L5, respectively. Multiple regression analysis revealed that sex had no significant effect on IVD degeneration whereas African ethnicity was associated with lower Thompson score at L1/L2, L2/L3, L3/L4, L4/L5 when compared with whites.

Conclusion. The relatively early degeneration at L5-S1 in all races and lower Thompson grade in donors of African ethnicity needs further investigation. Factors such as sagittal alignment, facet joint arthritis, and genetics potentially play a role in IVD degeneration.”
“Aim. To investigate antiproteinuric effect of spironolactone in patients with chronic kidney disease (CKD) treated with angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin II type 1 receptor blockers (ARBs). Methods.

It remains important for residents to acquire research skills bef

It remains important for residents to acquire research skills before continuing into practice or fellowship. The Clinical Research Education Study IPI-145 concentration Team program facilitates this education in an efficient, organized manner. (Obstet Gynecol 2011;117:1403-7) DOI: 10.1097/AOG.0b013e3182179705″
“Objective. The incorporation of airways conductance/resistance is a rare feature in clinical methacholine challenge test (MCT) protocols, and the majority

of pulmonary laboratories rely solely on the spirometric parameters. The importance and interpretation of an MCT demonstrating a significant decline in specific airway conductance specific airway conductance (sGaw), but not forced expiratory volume in one second (FEV1), remains undefined. This study sought to elucidate the clinical and physiologic phenotypes of individuals with a >= 40% sGaw decline but <20% FEV1 change. Methods. All subjects completed the Asthma Quality of Life Questionnaire (AQLQ), followed by standard MCT, with measurements of sGaw and an additional

independent measurement of resistance and reactance by impulse oscillation system (IOS) before and after MCT. Results. Of 201 subjects, 47(23.4%) were in Group 1 (FEV1 declined by >= 20%), 45(22.4%) were in Group 2 (non-significant FEV1 drop, sGaw declined >= 40%), and 109(54.2%) click here were in Group 3 (no significant decline in FEV1/sGaw). There was a nearly identical change in all oscillometric parameters and sGaw for Groups 1 and 2 versus Group 3. There were no differences between Groups

selleck inhibitor 1 and 2 in any AQLQ category, and Groups 1 and 2 were statistically different from Group 3. Conclusions. Our prospective study suggests that patients with a significant sGaw decline alone during MCT are a clinically and physiologically important hyper-reactivity phenotype-whose hyper-reactivity independently was confirmed to be nearly identical to those with an FEV1 decline. By failing to assess airways conductance/resistance, asthma may be inappropriately “”ruled out”" in similar to 20% of the patients referred for MCT. Based on this, standardized incorporation of body plethysmography and/or IOS to MCT protocols should be considered.”
“Empirical evidence indicates that cognitive consequences of cerebellar lesions tend to be mild and less important than the symptoms due to lesions to cerebral areas. By contrast, imaging studies consistently report strong cerebellar activity during tasks of action observation and action understanding. This has been interpreted as part of the automatic motor simulation process that takes place in the context of action observation. The function of the cerebellum as a sequencer during executed movements makes it a good candidate, within the framework of embodied cognition, for a pivotal role in understanding the timing of action sequences.

RESULTS: All patients underwent peripheral cannulation In 59 cas

RESULTS: All patients underwent peripheral cannulation. In 59 cases, vv-ECMO was placed in another facility with ECMO transport by helicopter or ambulance. The mean vv-ECMO support interval was 12 +/- 9.0 days (range, 1-67 days). During ECMO, 12 patients (7%) could be extubated and stepwise mobilized. Cannula-related A-1155463 mw complications during long-term support occurred in 14%, which was mostly minor bleeding. Overall

survival was 56%: 58 patients (33%) died during mechanical support, and 20 (11%) died after weaning from the system. The best outcome was noted in trauma patients. Risk factors were mainly advanced age and multiorgan failure.

CONCLUSION: Modern vv-ECMO is an excellent treatment in patients with severe ALF and should be more liberally used. J Heart Lung Transplant 2012;31:9-15 (C)

2012 International Society for Heart and Lung Transplantation. All rights reserved.”
“We present a study of the optical properties of GaN/AlN and InGaN/GaN quantum dot (QD) superlattices grown via plasma-assisted molecular-beam epitaxy, as compared to their quantum well (QW) counterparts. The three-dimensional/two-dimensional nature of the structures has been verified using atomic force microscopy and transmission electron microscopy. The QD superlattices present higher internal quantum efficiency as compared to the respective QWs as a result of the three-dimensional carrier Fer-1 cost localization in the islands. In the QW samples, photoluminescence (PL) measurements point out a certain degree of carrier localization due to structural defects or thickness

fluctuations, which is more pronounced in InGaN/GaN QWs due to alloy inhomogeneity. In the case of the QD stacks, carrier localization on potential fluctuations with a spatial extension smaller than the QD size is observed only for the InGaN QD-sample with the highest In content (peak emission around 2.76 eV). These results confirm the efficiency of the QD three-dimensional confinement in circumventing the potential BMS-754807 manufacturer fluctuations related to structural defects or alloy inhomogeneity. PL excitation measurements demonstrate efficient carrier transfer from the wetting layer to the QDs in the GaN/AlN system, even for low QD densities (similar to 10(10) cm(-3)). In the case of InGaN/GaN QDs, transport losses in the GaN barriers cannot be discarded, but an upper limit to these losses of 15% is deduced from PL measurements as a function of the excitation wavelength. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3590151]“
“BACKGROUND: Medical and psychosocial factors are related to 1-year outcomes in the Waiting for a New Heart Study. With increased use of mechanical circulatory support devices (MCSD) over the course of the study, we can now evaluate these variables as predictors of MCSD in an extended follow-up.

METHODS: Analyses focused on 313 MCSD-free patients (82% men; aged 53 +/- 11 years) newly listed for heart transplantation (HTx).

Conclusions: IF-RSP appears to be a feasible procedure in large-v

Conclusions: IF-RSP appears to be a feasible procedure in large-volume prostatomegaly. The entire prostate tissue is removed without compromising continence and potency. Larger series and longer-term follow-up are needed to evaluate the proper place of this approach.”
“Microorganisms can produce lipases with different

biochemical characteristics making necessary the screening of new lipase-producing strains for different industrial applications. selleck kinase inhibitor In this study, 90 microbial strains were screened as potential lipase producers using a sensitive agar plate method with a suitable medium supplemented with Tween 20 and also a liquid culture supplemented with olive oil. The highest cell growth and lipase production for Candida viswanathii were observed in triolein and oleic acid when used as the only pure carbon source. Renewable low-cost triacylglycerols supported the best cell growth, and olive oil was found to be the best inducer for lipase LY411575 datasheet production (19.50 g/L and 58.50 U). The selected conditions for enzyme production were found with yeast extract as nitrogen source and 1.5 % (w/v) olive oil (85.70 U) that resulted in

a good cell growth yield (Y-X/S = 1.234 g/g) and lipase productivity (1.204 U/h) after 72 h of shake-flask cultivation. C. viswanathii lipase presented high hydrolytic activity on esters bonds of triacylglycerols of long-chain, and this strain can be considered an important candidate Bindarit datasheet for future applications in chemical industries.”
“Background: The Millennium Cohort Study is a longitudinal cohort study designed in the late 1990s to evaluate how military service may affect long-term health. The purpose of this investigation was to examine characteristics of Millennium Cohort Study participants who responded to the open-ended question, and to identify and investigate the most commonly reported areas of concern.

Methods: Participants who responded during the 2001-2003 and 2004-2006 questionnaire cycles were included in this study (n = 108,129). To perform

these analyses, Latent Semantic Analysis (LSA) was applied to a broad open-ended question asking the participant if there were any additional health concerns. Multivariable logistic regression was performed to examine the adjusted odds of responding to the open-text field, and cluster analysis was executed to understand the major areas of concern for participants providing open-ended responses.

Results: Participants who provided information in the open-ended text field (n = 27,916), had significantly lower self-reported general health compared with those who did not provide information in the open-ended text field. The bulk of responses concerned a finite number of topics, most notably illness/injury, exposure, and exercise.