Validating the NIH LDL-C equation for provincial implementation in Alberta.

BACKGROUND: LDL-C, a cardiovascular disease risk assessment biomarker, is commonly calculated using the Friedewald equation. The NIH equation overcomes several limitations of the Friedewald equation. Consistent with the Canadian Society of Clinical Chemists (CSCC) lipid reporting recommendations, we assessed the NIH LDL-C equation in Alberta prior to its provincial implementation. METHODS: 1-year (01/01/2021-12/31/2021) of lipid results (n = 1,486,584 after data cleaning) were obtained from five analytical instrument groups used across Alberta. Analyses were performed on all data and after separating by age, analytical instrument group, and fasting status. The correlation between Friedewald- and NIH-calculated LDL-C and between Friedewald- and NIH-calculated LDL-C difference and each lipid parameter, was determined. The frequency of unreportable/inaccurate LDL-C results was compared between the two equations. The concordance between the two equations and with non-HDL-C was determined at LDL-C thresholds. Lastly, LDL-C calculated by Friedewald, NIH, and Martin-Hopkins equations was compared to density-gradient ultracentrifugation. RESULTS: Friedewald- and NIH-calculated LDL-C exhibit the strongest correlation when triglycerides ≤ 4.52 mmol/L. The difference between Friedewald- and NIH-calculated LDL-C increases with decreasing LDL-C concentration. The NIH equation yields fewer inaccurate results (0.35 % vs. 22.0 %). The percent agreement between equations was > 96 % at all LDL-C thresholds, suggesting most patients will not require treatment changes. NIH-calculated LDL-C exhibited better agreement with non-HDL-C when triglycerides ≤ 9.04 mmol/L and better correlated with LDL-C measured by ultracentrifugation (r2 = 0.926 vs. 0.775 (Friedewald) and 0.863 (Martin-Hopkins)). Results were consistent across age, analytical instrument group, and fasting status. CONCLUSIONS: Our findings demonstrate the benefits of implementing the NIH equation across Alberta.

Pediatric reference intervals for endocrine markers in healthy children and adolescents on the Liaison XL (DiaSorin) immunoassay system.

OBJECTIVES: Prominent physiological changes occurring throughout childhood and adolescence necessitate the consideration of age and sex in biomarker interpretation. Critical gaps exist in pediatric reference intervals (RIs) for specialized endocrine markers, despite expected influence of growth and development. The current study aimed to establish and/or verify RIs for six specialized endocrine markers on a specialized immunoassay system. METHODS: Samples were collected from healthy children and adolescents (5 to <19 years) and apparently healthy outpatients (0 to <5 years) as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). Serum samples were analysed for aldosterone, renin (plasma), thyroglobulin, anti-thyroglobulin, growth hormone, and insulin-like growth factor-1 (IGF-1) on the Liaison XL (DiaSorin) immunoassay platform. RIs (2.5th and 97.5th percentiles) were established for aldosterone, renin, thyroglobulin, anti-thyroglobulin, and growth hormone. Manufacturer-recommended pediatric RIs for IGF-1 were verified. RESULTS: Age-specific RIs were established for aldosterone, renin, and thyroglobulin, while no age-specific differences were observed for anti-thyroglobulin or growth hormone. IGF-1 was the only endocrine marker studied that demonstrated significant sex-specific differences. Manufacturer-recommended IGF-1 RIs were verified for children aged 6 to <19 years, while those for children aged 0 to <6 years did not verify. CONCLUSIONS: This study marks the first time that pediatric RIs for aldosterone and renin were established in the CALIPER cohort and highlights the dynamic changes that occur in water and sodium homeostasis during the first years of life. Overall, these data will assist pediatric clinical laboratories in test result interpretation and improve clinical decision-making for patients tested using Liaison immunoassays.

Hemoglobin variant in disguise.

BACKGROUND: Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants. However, molecular genetic analysis is a more definitive method for Hb variant identification. CASE REPORT: Here, we report a case of a 23-month-old male with results from capillary electrophoresis, gel electrophoresis (acid and alkaline), and high-performance liquid chromatography most consistent with HbS trait. Specifically, capillary electrophoresis showed slightly elevated HbF and HbA2, HbA of 39.4% and HbS of 48.5%. The HbS percentage was consistently higher than expected (typically 30-40%) for HbS trait with no concurrent thalassemic indices. The patient has not experienced any clinical complications due to the hemoglobinopathy and he is thriving. CONCLUSION: Molecular genetic analysis revealed the presence of compound heterozygosity for HbS and Hb Olupona. Hb Olupona is an extremely rare beta-chain variant that appears as HbA on all three common methods used for phenotypic Hb analysis. When the fractional concentration of Hb variants is unusual, more definitive methods should be used, such as mass spectrometry or molecular genetic testing. In this case, incorrectly reporting this result as HbS trait is unlikely to have a significant clinical impact, as current evidence suggests Hb Olupona is not a clinically significant variant.

Variation in processes and reporting of cerebrospinal fluid oligoclonal banding and associated tests and calculated indices across Canadian clinical laboratories.

OBJECTIVES: Multiple sclerosis is diagnosed based on clinical and laboratory findings, including cerebrospinal fluid (CSF) oligoclonal banding (OCB) analysis. The lack of updated CSF OCB laboratory guidelines in Canada has likely led to variation in processes and reporting across clinical laboratories. As a first step to developing harmonized laboratory recommendations, we examined current CSF OCB processes, reporting, and interpretation across all Canadian clinical laboratories currently performing this test. DESIGN AND METHODS: A survey of 39 questions was sent to clinical chemists at all 13 Canadian clinical laboratories performing CSF OCB analysis. The survey included questions regarding quality control processes, reporting practices for CSF gel electrophoresis pattern interpretation, and associated tests and calculated indices. RESULTS: The survey response rate was 100%. Most (10/13) laboratories use ≥2 CSF-specific bands (2017 McDonald Criteria) as their CSF OCB positivity cut-off and only 2/13 report the number of bands with every report. Most (8/13 and 9/13) laboratories report an inflammatory response pattern and monoclonal gammopathy pattern, respectively. However, the process for reporting and/or confirming a monoclonal gammopathy varies widely. Variation was observed for reference intervals, units, and the panel of reported associated tests and calculated indices. The maximum acceptable time interval between paired CSF and serum collections varied from 24 h to no limit. CONCLUSIONS: Profound variation exists in processes, reporting, and interpretation of CSF OCB and associated tests and indices across Canadian clinical laboratories. Harmonization of CSF OCB analysis is required to ensure continuity and quality of patient care. Our detailed assessment of current practice variation highlights the need for clinical stakeholder engagement and further data analysis to support optimal interpretation and reporting practices, which will aid in developing harmonized laboratory recommendations.

Defining blood gas analysis stability limits across five sample types.

Accurate reporting of blood gas samples is dependent upon following proper preanalytical sample handling requirements though there is variation for sample acceptability criteria across institutions. We examined five common sample types (arterial, venous, umbilical arterial, umbilical venous and capillary) stored at either room temperature or on crushed ice in a time series (0, 15, 30, 45, 60, 90, 180, 240 min) and applied local regulatory and/or institutional allowable performance limits to determine the need for cold preservation and/or maximum stability time for pH, pO2, pCO2, glucose, lactate, sodium, potassium, chloride, and ionized calcium where applicable in each sample type. Although changes in sample pO2 and/or lactate values were responsible, in part or in whole, for surpassing the allowable limits in nearly all sample types analyzed, this was not uniformly observed across sample types within the typical time limits that are referenced in literature. Furthermore, we demonstrated that cold preservation may not ubiquitously provide longer stability for blood gas specimens and this is dependent on the sample type and analyte in question. Nevertheless, these results demonstrate the known instability of pO2 and lactate and suggest that it may be possible to simplify the monitoring of preanalytical conditions by first evaluating pO2 and lactate in patient blood gas samples if applicable.

Sample stability of autoantibodies: A tool for laboratory quality initiatives.

OBJECTIVES: Serum autoantibody measurement aids in diagnosing and monitoring various autoimmune conditions. Defining autoantibody stability limits can improve laboratory process quality. Here, we define short-term stability in a refrigerator, long-term stability in a freezer, and the effect of freeze-thaw cycles to improve autoantibody testing procedures. DESIGN AND METHODS: Seventy-nine residual serum samples were used to assess the stability of 11 autoantibodies (anti-dsDNA, anti-Ro52, anti-Ro60, anti-SSB, anti-RNP, anti-Sm, anti-aCL-IgG, anti-tTG-IgA, anti-tTG-IgG, anti-DGP-IgA, anti-DGP-IgG) and two screening assays (CTD screen, ENA7 screen) on the BIO-FLASH (Inova Diagnostics). Three storage conditions were assessed: 8 weeks at 2-8 °C, 12 months at -30 °C, and 6 freeze (-30 °C)-thaw cycles. The maximum permissible instability (MPI) for each autoantibody was set as 2x %CV, calculated as the weighted average CV from cumulative QC data over the study period. RESULTS: By considering both mean percent difference (MPD) and mean absolute relative difference (MARD), all autoantibodies were stable for up to 8 weeks stored at 2-8 °C, except for CTD screen and anti-dsDNA. All autoantibodies were stable for up to 12 months stored at -30 °C, except ENA screen, anti-dsDNA, anti-DGP-IgA, anti-cardiolipin, and CTD screen. Lastly, all autoantibodies were stable for up to 6 freeze(-30 °C)-thaw cycles, except anti-RNP, anti-Ro60, anti-cardiolipin and anti-dsDNA. CONCLUSIONS: It is important to develop laboratory procedures derived from evidence-based stability limits. This study will aid laboratories in undertaking quality assurance and improvement initiatives to enhance autoantibody testing by ensuring appropriate storage conditions that consider defined sample stability limits.

Analytical performance evaluation of thyroid-stimulating hormone receptor antibody (TRAb) immunoassays.

BACKGROUND: Thyroid-stimulating hormone receptor (TSHR)-activating autoantibodies stimulate thyroid growth and hormone synthesis/secretion, causing hyperthyroidism of Graves' disease (GD). TRAb measurement helps diagnose GD and is an important first test in evaluating hyperthyroidism according to the recent American Thyroid Association guidelines. We compared the performance of the BRAHMS TRAK Kryptor (Thermo Scientific) and Roche cobas TRAb immunoassays for use in GD. METHOD: Method comparison (n = 40) and clinical agreement were assessed between the Kryptor, cobas e411, and cobas e601. The analytical performance of Kryptor and cobas e411 were assessed for within- and between-day imprecision across 20 days, linearity, functional assay sensitivity (FAS), dilution recovery, and cut-off verification. RESULTS: The Kryptor, e411, and e601 TRAb immunoassays correlated well (r > 0.95, overall percent agreement = 0.95, Cohen's kappa = 0.90). With a total allowable error of 20%, percent bias was within 13%, which was minimally negative at <20 IU/L, but highly positive (33%-34%) >20 IU/L. The Kryptor, but not e411, was linear across the claimed analytical measuring range (AMR). The claimed functional assay sensitivity (FAS), which was close to the clinical GD cut-off 1.8 IU/L, was verified for Kryptor and e411. CONCLUSION: Overall, our evaluation demonstrates acceptable comparability between TRAb immunoassays with in-house imprecision up to 13% and 10% on Kryptor and e411, respectively. While Roche has preferable calibration frequency and on-board reagent stability, both platforms demonstrate acceptable imprecision using patient samples at their claimed FAS, which is important for GD diagnosis. Diluted results (using a negative patient pool as diluent) exhibits proportional positive bias on the Kryptor relative to the Roche methods.

Pediatric reference intervals for calculated LDL cholesterol, non-HDL cholesterol, and remnant cholesterol in the healthy CALIPER cohort.

OBJECTIVES: Increased prevalence of pediatric obesity and associated co-morbidities has heightened the concern for cardiovascular disease (CVD) risk later in life. Although the fasting lipid profile is traditionally used to assess CVD risk, the non-fasting lipid profile may simplify lipid testing and better predict CVD risk. Unfortunately, non-fasting lipid reference values are limited, particularly for children. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has recruited thousands of healthy pediatric subjects to develop a pediatric reference interval database. Here, CALIPER reports pediatric reference intervals for non-fasting calculated low-density lipoprotein cholesterol (LDLc), non-high-density lipoprotein cholesterol (non-HDLc) and remnant cholesterol. METHODS: Non-fasting serum samples from the CALIPER cohort of community children and adolescents were previously analyzed for HDLc, total cholesterol, and triglycerides. These values were used to calculate LDLc, non-HDLc, and remnant cholesterol and subsequently establish reference intervals with corresponding 90% confidence intervals according to CLSI EP28-A3c guidelines. Reference intervals were also calculated using alternative statistical methods highlighted in recent literature. RESULTS: All three lipid parameters required an age partition at 1 year due to wider reference intervals in the first year of life. LDLc and non-HDLc required sex partitioning for subjects 1-<10 years. Non-HDLc upper reference limit was higher than the 2011 National Heart, Lung, and Blood Institute (NHLBII) pediatric recommended cut-offs, suggesting elevated atherogenic lipoproteins in a proportion of apparently healthy pediatric subjects. The LDLc upper reference limit (10-<19 year partition) was the same as the NHLBI cut-off, potentially due to lower calculated LDLc values in the non-fasting state. CONCLUSIONS: With the increased use of non-fasting lipid profiles, age- and sex-specific reference intervals and appropriate clinical decision limits are necessary for pediatric lipid monitoring. Our data supports the notion that appropriate decision limits, rather than reference intervals, should be used to interpret lipid levels in children as there is a high prevalence of hyperlipidemia in the apparently healthy pediatric population.

Biosecurity and the management of emergency animal disease among commercial beef producers in New South Wales and Queensland (Australia).

Australia places great importance on the prevention and management of emergency animal diseases (EAD), with strict quarantine measures offshore and at the border. Livestock producers are crucial for disease control onshore; however, limited information is available on commercial livestock producers' practices in relation to the management of disease risks. The aims of this paper are to investigate how commercial beef producers in Australia's Northern and Southern beef zones manage EADs and to identify drivers for effective biosecurity and EAD prevention. This paper forms part of a broader mixed methods research project involving an analysis of literature and current policies, qualitative semi-structured interviews with government and industry stakeholders and a cross-sectional study among beef producers. The cross-sectional study used a postal survey (n=182) and face-to-face interviews (n=34) to gather data on beef producers' knowledge and practices on biosecurity and EADs and their communication networks. Findings indicate that producers are uncertain about the roles and responsibilities of stakeholders involved in biosecurity and EAD management. This uncertainty may create confusion about EAD management and impact upon producers' willingness to report animal disease, with over 20% reporting the last veterinary contact more than five years ago and an additional 8.5% who had never contacted a veterinarian. Producers had a generally high awareness of the key sources of animal disease risk and they prioritise herd health planning as part of their everyday practices. Over 40% of producers had limited knowledge of the meaning of EAD; and EAD and biosecurity planning was given a low priority, primarily due to the perceived limited likelihood of an EAD event in Australia and the belief that EAD prevention is primarily the role of government. Only a moderate implementation of biosecurity practices, such as isolating incoming animals, having a single property entry point or keeping visitors' records was reported. If faced with an unusual disease event, most producers would contact their private or government veterinarian; however, in some instances most would also treat themselves and over a third would do nothing. Findings from this study suggest that there is a need for better coordination between stakeholders to encourage a shared biosecurity and EAD understanding and to communicate a consistent message to all stakeholders including producers. Further, there is a need for improving producer awareness of the importance of EAD prevention and biosecurity practices as well as the stakeholders' roles within the broader animal health system.

Impact of physician specialty on classification of physician-perceived patient severity for patients with osteoarthritis.

BACKGROUND: Physicians often classify patients' osteoarthritis (OA) severity subjectively. As treatment decisions are influenced by severity classifications, it is important to understand the factors that influence physicians' OA severity ratings. This research sought to empirically identify physician and patient characteristics that lead to a patient being perceived as having more severe OA. METHODS: Data were analyzed from the OA IX Disease Specific Program, a large cross-sectional survey of OA physicians and patients in Germany, the UK, and USA between September 2011 and January 2012. Eligible, consenting physicians completed a Patient Record Form (PRF) for 10 consecutive OA patients. The PRF asked physicians to report the patient's demographics [age, gender, body mass index (BMI), ethnicity], their assessment of the patients' symptom severity, treatment, probability for surgery, to rate their overall OA severity (mild, moderate or severe) and the factors that had influenced the rating. Chi-squared tests and analysis of variance were used to identify patient characteristics that significantly impacted physicians' OA severity ratings. Controlling for the significant patient characteristics, we then examined the impact of physician specialty on physician's OA severity ratings. Finally, we investigated the differences in physician-reported factors that influenced the physicians' rating of patients' severity between physician specialties. RESULTS: Three hundred and sixty-three physicians [220 primary care physicians (PCPs), 48 rheumatologists, 95 orthopedic surgeons] recruited 3561 patients. Patients with greater age and BMI, worse symptoms and greater health care use were given higher OA severity ratings. Controlling for these factors, orthopedic surgeons rated their OA patients as more severe than PCPs and rheumatologists [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI) 1.4-2.4]. Specialists (rheumatologists and orthopedic surgeons) were more likely than PCPs to use joint spaced narrowing based on X-ray and severity of joint deterioration radiographic severity to assess patients' OA severity (joint space narrowing: 79% and 78% vs 55%, P < 0.0001). CONCLUSIONS: Patient age, BMI, presence and severity of symptoms and health care use significantly impacted physicians' OA severity ratings, but radiographic changes appeared to be given greater weight among orthopedic surgeons and rheumatologists than PCPs when assessing patient severity. Whether these differences translate into different treatment recommendations for similar patients is unknown, and warrants study.

Slowing down of adult body mass index trend increases in England: a latent class analysis of cross-sectional surveys (1992-2010).

BACKGROUND: The prevalence of excess body weight, commonly measured as body mass index (BMI)≥25 kg m(-2), has increased substantially in many populations worldwide over the past three decades, but the rate of increase has slowed down in some western populations. OBJECTIVE: We address the hypothesis that the slowing down of BMI trend increases in England reflects a majority sub-population resistant to further BMI elevation. DESIGN: Pseudo-panel data derived from annual cross-sectional surveys, the Health Surveys for England (1992-2010). Trends in median BMI values were explored using regression models with splines, and gender-specific mixture model (latent class analysis) were fit to take an account of increasing BMI distribution variance with time and identify hidden subgroups within the population. SUBJECTS: BMI was available for 164 155 adults (men: 76 382; women: 87 773). RESULTS: Until 2001, the age-adjusted yearly increases in median BMI were 0.140 and 0.139 kg m(-2) for men and women, respectively, decreasing thereafter to 0.073 and 0.055 kg m(-2) (differences between time periods, both P-values<0.0001). The mixture model identified two components--a normal BMI and a high BMI sub-population--the proportions for the latter were 23.5% in men and 33.7% in women. The remaining normal BMI populations were 'resistant' with minimal increases in mean BMI values over time. By age, mean BMI values in the normal BMI sub-population increased greatest between 20 and 34 years for men; for women, the increases were similar throughout age groups (slope differences, P<0.0001). CONCLUSION: In England, recent slowing down of adult BMI trend increases can be explained by two sub-populations--a high BMI sub-population getting 'fatter' and a majority 'resistant' normal BMI sub-population. These findings support a targeted, rather than a population-wide, policy to tackle the determinants of obesity.

Transcriptomic insights into the molecular response of Saccharomyces cerevisiae to linoleic acid hydroperoxide.

Eukaryotic microorganisms are constantly challenged by reactive oxygen species derived endogenously or encountered in their environment. Such adversity is particularly applied to Saccharomyces cerevisiae under harsh industrial conditions. One of the major oxidants to challenge S. cerevisiae is linoleic acid hydroperoxide (LoaOOH). This study, which used genome-wide microarray analysis in conjunction with deletion mutant screening, uncovered the molecular pathways of S. cerevisiae that were altered by an arresting concentration of LoaOOH (75 µM). The oxidative stress response, iron homeostasis, detoxification through PDR transport and direct lipid ß-oxidation were evident through the induction of the genes encoding for peroxiredoxins (GPX2, TSA2), the NADPH:oxidoreductase (OYE3), iron uptake (FIT2, ARN2, FET3), PDR transporters (PDR5, PDR15, SNQ2) and ß-oxidation machinery (FAA2, POX1). Further, we discovered that Gpx3p, the dual redox sensor and peroxidase, is required for protection against LoaOOH, indicated by the sensitivity of gpx3Δ to a mild dose of LoaOOH (37.5 µM). Deletion of GPX3 conferred a greater sensitivity to LoaOOH than the loss of its signalling partner YAP1. Deletion of either of the iron homeostasis regulators AFT1 or AFT2 also resulted in sensitivity to LoaOOH. These novel findings for Gpx3p, Aft1p and Aft2p point to their distinct roles in response to the lipid peroxide. Finally, the expression of 89 previously uncharacterised genes was significantly altered against LoaOOH, which will contribute to their eventual annotation.

Ethnicity and childhood overweight/obesity in England.

BACKGROUND: Some studies suggest that British Afro-Caribbean girls and Pakistani girls have higher levels of obesity than girls in the general population of England. However, the interplay between child obesity, ethnicity, mother's socioeconomic status and other parental characteristics is unclear and requires exploration. OBJECTIVES: This study examines the relationship between child ethnicity and child overweight/obesity after controlling for a wide range of mothers' socioeconomic characteristics and parental overweight/obesity. METHODS: Health Survey for England data (1999 and 2004) are used to examine 7047 children aged 2-15 years. Body mass index (BMI) for children is classified using the International Obesity Task Force age-specific BMI thresholds for obesity and overweight. RESULTS: After controlling for a wide range of maternal socioeconomic characteristics and parental overweight/obesity, there are no ethnic differences in childhood overweight/obesity. CONCLUSIONS: Having overweight or obese parents is a stronger predictor of childhood overweight/obesity than ethnic origin of the child. Interventions aimed at reducing childhood overweight/obesity should focus on parental characteristics rather than the ethnicity of the child, but they also need to be sensitive to gender and ethnic differences. Future research should aim to repeat the analyses using a measure of abdominal obesity such as waist circumference, if data become available.

Impact of ocular symptoms on quality of life (QoL), work productivity and resource utilisation in allergic rhinitis patients--an observational, cross sectional study in four countries in Europe.

OBJECTIVE: It is hypothesised that the presence of ocular, in addition to nasal, symptoms among patients with allergic rhinitis (AR) results in poorer quality of life, reduced work productivity and increased resource utilisation. This study investigated the impact on quality of life, burden of illness and healthcare resources among 1640 AR patients. METHODS: Data were drawn from an observational cross-sectional study of consulting patients undertaken in May/June 2008 in four European countries. Doctors provided records for the next four to five patients presenting with AR who filled out a self-completion survey which included the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (RQOLQ) and the Pittsburgh Sleep Quality Index (PSQI). Propensity scoring allied to regression-type analysis was used to assess the extra burden associated with ocular symptoms utilising two comparison groups (patients with nasal-only symptoms versus those with nasal and ocular symptoms). The analysis controlled for differences between the groups on confounding variables age, gender, smoking status and co-morbidities. The analysis was conducted twice, once controlling for differences between the groups in nasal severity and once without, recognising that it is not clear whether or not increased nasal severity symptoms are naturally associated with ocular symptoms. The severity of ocular symptoms as opposed to their presence alone was also assessed on outcome measures using regression type methods. RESULTS: A total of 1009 patient records met the inclusion criteria, of whom 69% presented with both ocular and nasal symptoms. The results show that the presence of ocular symptoms reduces quality of life, reduces work productivity and increases resource utilisation irrespective of whether differences in severity of nasal symptoms are accounted for between the comparison groups. Patients with nasal and ocular symptoms require more healthcare consultations. All work-related domains were statistically different, with the presence of ocular symptoms associated with greater impact on work hours missed and impairment while working. For each of the above this was the case regardless of whether or not adjustment was made for nasal severity (both p < 0.05). Patients with nasal and ocular symptoms also record an additional half a day more time off work in the last 3 months as a result of AR (nasal severity unadjusted or adjusted, both p < 0.05). Clinically meaningful differences were found in overall quality of life score as represented by RQLQ, with a mean score increase of 0.6 (nasal severity unadjusted) and 0.5 (nasal severity adjusted) associated with the presence of ocular symptoms (both p < 0.05). With regard to sleep quality, the presence of ocular symptoms was associated with a mean increase in PSQI of 1 when no adjustment was made for nasal severity (p < 0.05). When nasal severity was adjusted for, no significant difference was observed. Similarly, for the number of prescribed medications, when no adjustment was made for nasal severity, patients with ocular symptoms were observed to receive a significantly higher number of AR drugs (+0.19, p < 0.05) whereas with nasal severity adjusted for the difference was +0.17 which was not significant. In addition, with the exception of the number of AR drugs prescribed, for all outcome variables, the severity of ocular symptoms, and not just their presence, had a detrimental impact on the outcome. LIMITATIONS: Since patients were recruited via the physician, the study aim was to represent the consulting population. In addition, it cannot be fully excluded that the likelihood for an individual patient to complete a questionnaire is influenced by differences in patient typology compared with those patients who chose not to complete. Given the geographical dispersion of the sample patients, it may be reasonable to assume possible differences in the intensity of the AR season based on latitude. CONCLUSION: The added presence of ocular symptoms in AR patients suffering with nasal symptoms deteriorates patients' quality of life, leads to greater lost productivity and places higher burden on resource utilisation. Studies are therefore needed to test whether treatment options that address ocular in addition to nasal symptoms will improve quality of life and reduce both direct and indirect resource use associated with AR.

Communication challenges in surgical oncology.

In this essay we set out clinical communication challenges in surgical oncology. We draw directly on relevant examples where they are available. Otherwise, we refer to the more generic surgical and medical literature. We offer 'macro' and 'micro' perspectives on clinical communication. That is, exploring communication challenges at the level of the organization and between individuals, doctors and patients and interprofessionally across different settings. Training content and methods are reported that address the complex communication challenges associated with surgical oncology. Innovations in simulation-based education offer exciting new opportunities for formative and summative assessment. We outline limitations of the essay and finally propose the content of a surgical oncology communication program.

Physician and patient survey of allergic rhinitis: methodology.

Methodology for Disease Specific Programme (DSP) surveys designed by Adelphi Group Products is used each year to survey patients and physicians on their perceptions of treatment effectiveness, symptoms and impact of diseases. These point-in-time surveys, conducted in the USA and Europe (France, Germany, Italy, Spain and UK), provide useful information on the real-world management and treatment of diseases. This paper describes the methodology for the DSP survey in allergic rhinitis, detailing the preparation of materials, recruitment of physicians, data collection and data management.

Generation of a novel Saccharomyces cerevisiae strain that exhibits strong maltose utilization and hyperosmotic resistance using nonrecombinant techniques.

A yeast strain capable of leavening both unsugared and sweet bread dough efficiently would reduce the necessity of carrying out the expensive procedure of producing multiple baker's yeast strains. But issues involving the use of genetically modified foods have rendered the use of recombinant techniques for developing yeast strains controversial. Therefore, we used strong selection and screening systems in conjunction with traditional mass mating techniques to develop a strain of Saccharomyces cerevisiae that efficiently leavens both types of dough.

Identification of a Saccharomyces cerevisiae gene that is required for G1 arrest in response to the lipid oxidation product linoleic acid hydroperoxide.

Reactive oxygen species cause damage to all of the major cellular constituents, including peroxidation of lipids. Previous studies have revealed that oxidative stress, including exposure to oxidation products, affects the progression of cells through the cell division cycle. This study examined the effect of linoleic acid hydroperoxide, a lipid peroxidation product, on the yeast cell cycle. Treatment with this peroxide led to accumulation of unbudded cells in asynchronous populations, together with a budding and replication delay in synchronous ones. This observed modulation of G1 progression could be distinguished from the lethal effects of the treatment and may have been due to a checkpoint mechanism, analogous to that known to be involved in effecting cell cycle arrest in response to DNA damage. By examining several mutants sensitive to linoleic acid hydroperoxide, the YNL099c open reading frame was found to be required for the arrest. This gene (designated OCA1) encodes a putative protein tyrosine phosphatase of previously unknown function. Cells lacking OCA1 did not accumulate in G1 on treatment with linoleic acid hydroperoxide, nor did they show a budding, replication, or Start delay in synchronous cultures. Although not essential for adaptation or immediate cellular survival, OCA1 was required for growth in the presence of linoleic acid hydroperoxide, thus indicating that it may function in linking growth, stress responses, and the cell cycle. Identification of OCA1 establishes cell cycle arrest as an actively regulated response to oxidative stress and will enable further elucidation of oxidative stress-responsive signaling pathways in yeast.