Audit quality : earnings management in the context of the 1997 Asian crisis

This study assumes that evidence regarding audit quality can be derived from the level of earnings management reflected in reported abnormal or discretionary accruals. Given this assumption, audit quality is examined in the context of the 1997 Asian financial crisis using data from Malaysia. Examining audit quality in its association with earnings management across differential macroeconomic periods provides insights that may be otherwise masked. The period of the crisis is partitioned between pre-crisis (1994-1996), crisis (1997-1998) and post-crisis (1999). Using a robust approach to the measurement of abnormal accruals, the association of Big 5/non-Big 5 and Industry Specialist/Industry non-specialist auditors with both the levels of, and change in levels of, abnormal accruals is investigated across and within the crisis sub-periods from 1994-1999. Audit quality is found to be associated with abnormal accruals, and differentially so across macroeconomic period with greater constraint evident post-crisis.

Do maternally derived antibodies and early immune experience shape the adult immune response?

1. Immunological imprinting by maternally derived antibodies has been proposed to have both positive and negative consequences for offspring immunity in early and adult life. However, few studies of maternal effects on immunity have followed individuals past the juvenile stages.

2. Using laboratory Japanese quail, we developed a novel method of directly manipulating yolk antibodies of neonates, and then followed individuals through a series of immune challenges until they were of reproductive age.

3. Our method of directly injecting purified antibodies into the yolk sac of newly hatched chicks successfully elevated the plasma titres of specific anti-KLH IgY in neonates. This allows us to test whether differences in neonatal anti-KLH IgY affect immunity at the juvenile and adult stages of life.

4. We found little evidence for an effect of maternal antibodies on juvenile stage immune response, in contrast to results from previous studies. Adult immune response depended largely on the magnitude of the juvenile immune response regardless of the identity of the antigen in the juvenile immune challenge, and did not depend on neonatal IgY titres. Our results are consistent with a priming effect of early immune experience on adult stage immune responsiveness, but we found no evidence of carryover effects of yolk-derived antibodies on adult immunity.

5. This study employs new methodology for investigation of maternal antibodies and presents results suggesting that further studies of maternal effects on immunity will require careful consideration of the numerous ways maternally derived yolk components can impact the different types of immune response.

Ecological and life-history factors influencing the evolution of maternal antibody allocation : a phylogenetic comparison

Maternally derived yolk antibodies provide neonates with immune protection in early life at negligible cost to mothers. However, developmental effects on the neonate's future immunity are potentially costly and thus could limit yolk antibody deposition. The benefits to neonatal immunity must be balanced against costs, which may depend on neonate vulnerability to pathogens, developmental trajectories and the immunological strategies best suited to a species' pace of life. We measured yolk antibodies and life-history features of 23 species of small Neotropical birds and assessed the evidence for each of several hypotheses for life history and ecological effects on the evolution of yolk antibody levels. Developmental period and yolk antibodies are negatively related, which possibly reflect the importance of humoral immune priming through antigen exposure, and selection to avoid autoimmunity, in species with a slower pace of life. There is also a strong relationship between body size and yolk antibody concentration, suggesting that larger species are architecturally equipped to produce and transfer higher concentrations of antibodies. These results suggest that developmental effects of maternally derived antibodies, such as imprinting effects on B-cell diversity or autoimmune effects, are important and deserve more consideration in future research.

Systemic activation of dendritic cells by toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity

The mechanisms responsible for the immunosuppression associated with sepsis or some chronic blood infections remain poorly understood. Here we show that infection with a malaria parasite (Plasmodium berghei) or simple systemic exposure to bacterial or viral Toll-like receptor ligands inhibited cross-priming. Reduced cross-priming was a consequence of downregulation of cross-presentation by activated dendritic cells due to systemic activation that did not otherwise globally inhibit T cell proliferation. Although activated dendritic cells retained their capacity to present viral antigens via the endogenous major histocompatibility complex class I processing pathway, antiviral responses were greatly impaired in mice exposed to Toll-like receptor ligands. This is consistent with a key function for cross-presentation in antiviral immunity and helps explain the immunosuppressive effects of systemic infection. Moreover, inhibition of cross-presentation was overcome by injection of dendritic cells bearing antigen, which provides a new strategy for generating immunity during immunosuppressive blood infections.

Economic network structures, growth and poverty

While investors are advised to diversify in order to manage risk, developing countries are advised instead to liberalise their trade regimes and specialise according to their current comparative advantage. This study uses 67 regions of the GTAP database to investigate the effects of unilateral liberalisation and its impacts on countries’ economic structures and the extent to which this affects countries’ vulnerability to an economic shock. While liberalisation resulted in improvements in GDP and welfare on average, there were significant variations. A number of countries experienced contractions in their GPDs and declines in welfare. While there was no evidence of a relationship between the percentage change in GDP and the initial export or output concentration, there was a positive relationship between the percentage change in GDP and the percentage change in export and output concentrations. On average, increases in GDP following liberalisation were associated with increases in concentration in both the export sector and in overall industrial output and also reductions in the fraction of unskilled labour employed by the main export sector. Initial GDP per capita has no significant effect, implying that once concentration measures and the fraction of costs in the main export are accounted for, the per capita income levels of a country show no systematic effects on the percentage change in GDP induced by the liberalisation. For developing countries undergoing unilateral liberalisation, the results imply that they are likely to experience an increase in GDP, but an increase accompanied by more highly concentrated industrial output and exports, and also a lower fraction of main export costs due to unskilled labour. Following liberalisation, the responses of liberalised and non-liberalised versions of the region’s economies to a shock were compared. The rest of the world’s productivity in the country’s main export was increased by 10%, with the liberalised economies faring marginally worse on average in welfare and terms of trade effects, but slightly better on GDP effects. When the net effects of the initial liberalisation and subsequent technology shock were compared, countries were better off on average if they had liberalised. But this average masked important sectoral differences. Countries specialising in sectors with high proportions of own-commodity inputs in their main export’s total cost, such as manufacturing, did best, while those specialising in food tended to suffer welfare declines. Higher levels of export and output concentration also tended to reduce welfare. This suggests that increased concentration does indeed make countries more vulnerable to certain economic shocks. Finally, the economic network structures of the two extreme cases, Tanzania and Vietnam are compared visually as an aid to interpretation.

Diagnosing bipolar disorder : how can we do it better?

• Accurate diagnosis of bipolar disorder is essential for effective treatment.

• The diagnosis of bipolar disorder is particularly complex, resulting in lengthy delays between first presentation and initiation of appropriate therapy. Inappropriate therapy destabilises the course and outcome of the disease.

• Although the defining features of bipolar disorder are manic or hypomanic episodes, patients typically present for treatment of depression and commonly deny symptoms of mood elevation.

• A correct diagnosis can easily be masked by comorbidities, personality issues and complex phenomenology.

• A diagnosis of bipolar disorder can be assisted by:

   → asking about symptoms of mania or hypomania in every patient presenting with symptoms of depression.

   → recognising mixed states in which manic and depressive symptoms occur simultaneously.

   → identifying the features of bipolar depression that distinguish it from unipolar depression.

• There is a risk of over-diagnosis of bipolar disorder among patients who are histrionic, show abnormal illness behaviour MJA 2006; 184: 459–462 and/or have issues of secondary gain.

Use of a photographic manipulation tool to assess corneal vascular response

Purpose. Corneal vasculature change in contact lens wearers has been linked to the level of hypoxia within the cornea. To assess the impact a treatment has on limbal vessels, a sensitive method of measurement and quantification is required.

Methods. A group of 21 highly myopic, hydrogel wearers, with preexisting signs of corneal hypoxia, were enrolled into a study where they wore sifilcon A silicone hydrogel lenses (Dk/t = 117), on a daily wear basis for 9 months. At all scheduled visits, photographs were taken of the superior, inferior, temporal, and nasal limbal regions which were then imported into Adobe Photoshop. A red-free filter was applied to enhance the contrast of the blood columns. In each quadrant, the length of the longest visible blood column was measured and the blood columns that penetrated >0.5 mm into the cornea were counted. A control group of 11 non-lens wearers was recruited. Their photographs were taken at the beginning of the study and 9 months later. An independent, masked observer assessed the photographs.

Results. There was a significant decrease in the maximum penetration of the blood column in all quadrants (p < 0.001) from baseline to the 9-month visit (e.g., superior: baseline 0.84 ± 0.39 mm; 9 months 0.63 ± 0.20 mm). There was also significant reduction in the number of visible blood columns longer than 0.5 mm in each quadrant (p < 0.001) from baseline to 9 months in all quadrants (e.g., superior: baseline 14.0 ± 8.2; 9 months 6.5 ± 6.0). The control group showed no change over time for the maximum blood column length (p = 0.638) or the number of columns >0.5 mm (p = 0.341).

Conclusions. A group of highly myopic subjects exhibited reduction in the maximum length and number of blood columns in the cornea when refit with a highly permeable silicone hydrogel material. The use of photography, along with Adobe Photoshop software, provides a reliable way of measuring corneal vascular responses over time.

Measurement of the refractive index of soft contact lenses during wear

Purpose: To determine whether the refractive index (RI) of a soft contact lens can be evaluated using refractometry while the lens remains on the eye and to compare this with more traditional ex vivo RI measurements.

Methods: A slitlamp apparatus was modified to incorporate a customized Atago hand refractometer. With a double-masked study design, nine adapted symptomatic soft contact lens wearers wore a contact lens in each eye (lotrafilcon B and etafilcon A) in a randomized order. In vivo RI was determined from the relative Brix scale measurements immediately after lens insertion and after 1 and 10 hr of lens wear. Ex vivo refractometry was performed after 10 hr of lens wear for comparison. Means ± standard errors of the means are reported.

Results: In vivo RI values at baseline were 1.422 ± 0.0004 (lotrafilcon B) and 1.405 ± 0.0021 (etafilcon A); after 1 hr of lens wear, values were 1.423 ± 0.0006 and 1.408 ± 0.0007, respectively; and after 10 hr of lens wear, values were 1.424 ± 0.0004 and 1.411 ± 0.0010, respectively. Ex vivo RI values at the end of the 10 hr wearing period were 1.424 ± 0.0003 (lotrafilcon B) and 1.412 ± 0.0017 (etafilcon A). The change in in vivo RI across the day was statistically significant for the etafilcon A lens (repeated-measures analysis of variance, P<0.01) but not for the lotrafilcon B lens (P>0.05).

Conclusions: This novel adaptation of refractometry was able to measure the RI of soft contact lenses during wear (without lens removal). End of day RI measurements using in vivo and ex vivo refractometry were comparable with each other. Future work is required to determine whether this in vivo method can improve our understanding of the relationships between soft contact lens RI, hydration, on-eye lens performance, and symptomology.

Early symptomatic presbyopes - what correction modality works best?

Purpose: To compare the performance of a low-addition silicone hydrogel multifocal soft lens with other soft lens correction options in a group of habitual soft lens wearers of distance correction who are symptomatic of early presbyopia.

Method: This clinical study was designed as a prospective, double-masked, randomized, crossover, dispensing trial consisting of four 1-week phases, one for each of the correction modalities: a low-addition silicone hydrogel multifocal soft lens, monovision, habitual correction, and optimized distance visual correction. The prescriptions of all modalities were finalized at a single fitting visit, and the lenses were worn according to a randomized schedule. All lenses were made from lotrafilcon B material. A series of objective vision tests were conducted: high- and low-contrast LogMAR under high- and low-room lighting conditions, stereopsis, and critical print size. A number of other data collection methods used were novel: some data were collected under controlled laboratory-based conditions and others under real-world conditions, some of which were completed on a BlackBerry hand-held communication device.

Results: All participants were able to be fit with all four correction modalities. Objective vision tests showed no statistical difference between the lens modalities except in the case of low-contrast near LogMAR acuity under low-lighting levels where monovision (+0.29 ± 0.10) performed better than the multifocal (+0.33 ± 0.11, P=0.027) and the habitual (+0.37 ± 0.12, P<0.001) modalities. Subjective ratings indicated a statistically better performance provided by the multifocal correction compared with monovision, particularly for the vision associated with driving tasks such as driving during the daytime (93.3 ± 8.8 vs. 84.2 ± 23.7, P=0.05), at nighttime (88.8 ± 11.7 vs. 74.9 ± 23.6, P=0.001), any associated haloes or glare (92.0 ± 10.6 vs. 78.0 ± 22.8, P=0.003), and observing road signs (90.1 ± 11.8 vs. 79.4 ± 20.2, P=0.027). Preference for the multifocal compared with monovision was also reported when watching television (95.0 ± 6.4 vs. 82.6 ± 20.1, P=0.001) and when changing focus from distance to near (87.0 ± 13.4 vs. 66.1 ± 32.2, P<0.001).

Conclusions: For this group of early presbyopes, the AIR OPTIX AQUA MULTIFOCAL-Low Add provided a successful option for visual correction, which was supported by the results of subjective ratings, many of which were made during or immediately after performing such activities as reading, using a computer, watching television, and driving. These results suggest that making a prediction of success or not based on consulting room acuity tests alone is probably unwise.

An investigation of the efficacy of a novel ocular lubricant

Objective: To investigate the efficacy of a novel ocular lubricant compared with a commercially marketed ocular lubricant in a group of noncontact lens wearers currently using over-the-counter products for the management of symptoms of moderate to severe dry eye.

Methods: This was a prospective, double-masked study that randomized 110 subjects in a ratio of 1:1 to receive a novel ocular lubricant (test group) or a marketed ocular lubricant (control group). Subjects were instructed to instill the lubricant eye drops at least three times daily. After enrollment, subjects were evaluated at baseline and at 7 and 30 days. They were also required to complete a series of home-based subjective questionnaires after 15 days. Main outcomes were subjective symptoms and objective clinical assessment at 7 and 30 days.

Results: The test group had higher overall comfort ratings than the control group (P = 0.012). Seventy-one percent of the test group and 57% of the control group said the drops used “somewhat” or “definitely” improved ocular comfort; 62% of the test group had greater end-of-day comfort compared with 45% of the control group (P = 0.015). There were no between-group differences in visual acuity, tear quality or quantity, corneal staining, conjunctival staining, or bulbar and limbal conjunctival hyperemia.

Conclusions: The novel ocular lubricant offers equivalent or superior comfort compared with a marketed lubricant eye drop. Objective clinical outcomes were not statistically significantly different between the two groups.

Multipurpose disinfecting solutions and their interactions with a silicone hydrogel lens

Purpose: To assess the compatibility of a new silicone hydrogel lens, asmofilcon A (with four multipurpose disinfecting solutions: OPTIFREE RepleniSH, ReNu MultiPlus, Solo-Care Aqua and MeniCare Soft). Ocular responses and subjective responses were monitored with each lens-care system combination.

Methods: The study was conducted as a prospective, bilateral, clinical trial with a single-masked investigator, and randomized cross-over design with four phases, (one for each care system). Each study phase comprised of two consecutive days of lens wear where the lenses were inserted on day 1 directly from the blister-packs and worn for over 8 hr, then inserted on day 2 after overnight disinfection with one of the study lens care systems. Twenty-five adapted soft contact lens wearers who were able to wear their habitual lenses comfortably for more than 12 hr were recruited.

Results: There were statistically significant differences in corneal staining found for all the lens-care systems when comparing the results of day 1 (from the blister pack) with day 2 (following care system use) (P < 0.05). ReNu MultiPlus solution had the highest grade for corneal staining at the 2-hr time point on day 2 which then decreased by 6 hr (P < 0.05). There was no difference between the lens care systems and the rating of subjective comfort over either of the two days. The rating of dryness and burning sensations were only slightly increased at 6 hr for all lens care systems except ReNu MultiPlus where burning was highest on insertion (P < 0.05).

Conclusion: Corneal staining observed in this study does not seem to have been related to the presence of polyhexamethylene biguanide (0.0001% wv) that was present in three of the four care systems. Only one care system (ReNu MultiPlus) demonstrated an associated level of corneal staining that was statistically significant; however, this was not considered to be of clinical relevance. These results suggest that using this novel surface-treated silicone hydrogel lens may result in less lens and lens care-related interactions.

Clinical evaluation of long-term users of two contact lens care preservative systems

Purpose: To clinically evaluate long-term users of two different contact lens care preservative systems and to investigate whether prolonged use is associated with an increase in the prevalence of dry eye.

Methods: Eighty-nine wearers of group IV hydrogel or silicone hydrogel lenses participated in this one-visit, investigator-masked study. Subjects were required to have consistently used a polyhexamethylene biguanide (PHMB) or polyquaternium-1 (PQT) based solution for 2 years. Consistent use was defined as 80% for the past 2 years and 100% for the past year. Clinical assessments included: average and comfortable wear time; overall and end-of-day comfort; signs of dryness, discomfort, burning or stinging, grittiness or scratchiness and visual changes; non-invasive and fluorescein break-up-time; pre-ocular tear film lipids, tear meniscus height, Schirmer and fluorescein clearance tests; limbal and bulbar hyperemia; palpebral roughness; corneal and conjunctival staining; lens front surface wetting; and lens film deposits.

Results: Significantly more grittiness or scratchiness was reported by subjects using a PHMB-containing system (67% vs. 44%; P = 0.02). Palpebral roughness and hyperemia were significantly greater in the PHMB group wearing group IV lenses (P = 0.01 and P = 0.05, respectively). Corneal staining was significantly higher in the PHMB users in all four peripheral sectors (P < 0.01). Nasal and temporal conjunctival staining was also significantly higher for users of PHMB-containing systems (P < 0.05). Front surface lens wettability was significantly better for group IV PQT users compared to PHMB users (P = 0.008), with 84% vs. 72%, respectively, with lenses graded by the investigator as having good or excellent wettability. Significantly higher levels of lens front surface film deposits were noted with PHMB users (P = 0.007), with 58% of group IV lenses treated with PHMB compared with 38% of group IV lenses treated with PQT showing some lens front surface film deposition. No significant differences between the two preservative system groups were noted for the range of dry eye evaluations nor the remaining clinical assessments.

Conclusions: Differences in both ocular and lens characteristic were observed between long-term users of two preservative systems used in many contact lens multi-purpose solutions. The findings from this study did not support the hypothesis that prolonged use of PHMB-containing solutions leads to dry eye. Additional studies including a larger sample size and perhaps longer use of the systems could help to further elucidate differences in clinical performance between systems.

Comfort and adaptation to silicone hydrogel lenses for daily wear

Objectives. To investigate initial comfort and adaptation of currently successful low oxygen transmissibility soft lens wearers refitted with silicone hydrogel (SH) lenses for daily wear.

Methods. Fifty-five subjects were enrolled in a subject-masked 5-month clinical trial in which they wore 5 SH lenses in a randomized, crossover design. Comfort, burning, and dryness were rated on scales of 0 to 100 immediately on insertion and the time for lens settling was recorded. Symptoms were then rated at various times, using BlackBerry wireless communication devices (Research in Motion, Waterloo, Canada), during the day for 2 cycles of 2 weeks wear for each lens type.

Results. Comfort immediately on insertion varied between lens types (P=0.002). All lens types were reported by the subjects to have settled within 30 to 45 sec of insertion (P=0.14) and settled comfort was greater than comfort immediately on insertion (P<0.001). Comfort within the first hour of wear also varied between lens types (P=0.02). Comfort during the day decreased significantly for all lenses (P=0.001), but there was no difference between lenses (P=0.19) and no effect of lens age (P=0.15). The wearing times were greater with the SH lenses than the habitual lenses worn before study commencement (P=0.001). Overall performance of the lenses after 4 weeks was high, with no difference between lenses (P=0.45).

Conclusions. Initial comfort and adaptation to all SH lenses were good and no differences in the overall ratings were found between the 5 SH lenses investigated. Decreased comfort was noted later in the day with all lens types, but longer wearing times were reported with the SH lenses than previous hydroxyethyl methacrylate-based lenses.

Glaucoma and on-road driving performance

PURPOSE. To investigate the on-road driving performance of patients with glaucoma.

METHODS. The sample comprised 20 patients with glaucoma and 20 subjects with normal vision, all licensed drivers, matched for age and sex. Driving performance was tested over a 10-km route incorporating 55 standardized maneuvers and skills through residential and business districts of Halifax, Nova Scotia, Canada. Testing was conducted by a professional driving instructor and assessed by an occupational therapist certified in driver rehabilitation, masked to participant group membership and level of vision. Main outcome measures were total number of satisfactory maneuvers and skills, overall rating, and incidence of at-fault critical interventions (application of the dual brake and/or steering override by the driving instructor to prevent a potentially unsafe maneuver). Measures of visual function included visual acuity, contrast sensitivity, and visual fields (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA; mean deviation [MD] and binocular Esterman points).

RESULTS. There was no significant difference between patients with glaucoma (mean MD = −1.7 dB [SD 2.2] and −6.5 dB [SD 4.9], better and worse eyes, respectively) and control subjects in total satisfactory maneuvers and skills (P = 0.65), or overall rating (P = 0.60). However, 12 (60%) patients with glaucoma had one or more at-fault critical interventions, compared with 4 (20%) control subjects (odds ratio = 6.00, 95% CI, 1.46–24.69; higher still after adjustment for age, sex, medications and driving exposure), the predominant reason being failure to see and yield to a pedestrian. In the glaucoma group, worse-eye MD was associated with the overall rating of driving (r = 0.66, P = 0.002).

CONCLUSIONS. This sample of patients with glaucoma with slight to moderate visual field impairment performed many real-world driving maneuvers safely. However, they were six times as likely as subjects with normal vision to have a driving instructor intervene for reasons suggesting difficulty with detection of peripheral obstacles and hazards and reaction to unexpected events.

Effects of modifying the tRNA(3Lys) anticodon on the initiation of human immunodeficiency virus type 1 reverse transcription

tRNA(3Lys) is a primer for reverse transcription in human immunodeficiency virus type 1 (HIV-1), and the anticodon of tRNA(3Lys) has been implicated in playing a role in both its placement onto the HIV-1 genome and its interaction with HIV-1 reverse transcriptase (RT). In this work, the anticodon in a tRNA(3Lys) gene was changed from UUU to CUA (tRNA(3Lys)Su+) or, in addition, G-73 was altered to A (tRNA(3Lys)Su+G73A). COS-7 cells were transfected with either wild-type or mutant tRNA(3Lys) genes, and both the wild-type and mutant tRNA(3Lys) produced were purified by using immobilized tRNA-specific hybridization probes. Each mutant tRNA(3Lys) was tested for its ability to prime reverse transcription in vitro, either alone or in competition with wild-type tRNA(3Lys). Short RT extensions of wild-type and mutant tRNALys could be distinguished from each other by their different mobilities in one-dimensional single-stranded conformation polymorphism polyacrylamide gel electrophoresis. These reverse transcription products show that heat-annealed tRNA(3Lys)Su+ has the same ability as heat-annealed wild-type tRNA(3Lys) to prime RT and competes equally well with wild-type tRNA(3Lys) for priming RT. tRNA(3Lys)Su+G73A has 60% of the wild-type ability to prime RT but competes poorly with wild-type tRNA(3Lys) for priming RT. However, the priming abilities of wild-type and mutant tRNA(3) are quite different when in vivo-placed tRNA is examined. HIV-1 produced in COS cells transfected with a plasmid containing both the HIV-1 proviral DNA and DNA coding for tRNA(3Lys)Su+ contains both endogenous, cellular wild-type tRNA(3Lys) and mutant tRNA(3Lys). When total viral RNA is used as the source of primer tRNA placed onto the genomic RNA in vivo, only wild-type tRNA(3Lys) is used as a primer. If the total viral RNA is first heated and exposed to hybridizing conditions, then both the wild-type and mutant tRNA(3Lys) act as primers for RT. These results indicate that the tRNA(3Lys)Su+ packaged into the virions is unable to act as a primer for RT, and a model is proposed to explain the disparate results between heat-annealed and in vivo-placed primer tRNA.