Association and linkage analyses of restriction fragment length polymorphisms for the human renin and antithrombin III genes in essential hypertension

Essential hypertension is a highly hereditable disorder in which genetic influences predominate over environmental factors. The molecular genetic profiles which predispose to essential hypertension are not known. In rats with genetic hypertension, there is some recent evidence pointing to linkage of renin gene alleles with blood pressure. The genes for renin and antithrombin III belong to a conserved synteny group which, in humans, spans the q21.3-32.3 region of chromosome I and, in rats, is linkage group X on chromosome 13. The present study examined the association of particular human renin gene (REN) and antithrombin III gene (AT3) polymorphisms with essential hypertension by comparing the frequency of specific alleles for each of these genes in 50 hypertensive offspring of hypertensive parents and 91 normotensive offspring of normotensive parents. In addition, linkage relationships were examined in hypertensive pedigrees with multiple affected individuals. Alleles of a REN HindIII restriction fragment length polymorphism (RFLP) were detected using a genomic clone, λHR5, to probe Southern blots of HindIII-cut leucocyte DNA, and those for an AT3 Pstl RFLP were detected by phATIII 113 complementary DNA probe. The frequencies of each REN allele in the hypertensive group were 0.76 and 0.24 compared with 0.74 and 0.26 in the normotensive group. For AT3, hypertensive allele frequencies were 0.49 and 0.51 compared with normotensive values of 0.54 and 0.46. These differences were not significant by χ2 analysis (P > 0.2). Linkage analysis of a family (data from 16 family members, 10 of whom were hypertensive), informative for both markers, without an age-of-onset correction, and assuming dominant inheritance of hypertension, complete penetrance and a disease frequency of 20%, did not indicate linkage of REN with hypertension, but gave a positive, although not significant, logarithm of the odds for linkage score of 0.784 at a recombination fraction of 0 for AT3 linkage to hypertension. In conclusion, the present study could find no evidence for an association of a REN HindIII RFLP with essential hypertension or for a linkage of the locus defined by this RFLP in a family segregating for hypertension. In the case of an AT3 Pstl RFLP, although association analysis was negative, linkage analysis suggested possible involvement (odds of 6:1 in favour) of a gene located near the 1q23 locus with hypertension in one informative family.

Allelic variation at a single gene increases food value in a drought-tolerant staple cereal

The production of adequate agricultural outputs to support the growing human population places great demands on agriculture, especially in light of ever-greater restrictions on input resources. Sorghum is a drought-adapted cereal capable of reliable production where other cereals fail, and thus represents a good candidate to address food security as agricultural inputs of water and arable land grow scarce. A long-standing issue with sorghum grain is that it has an inherently lower digestibility. Here we show that a low-frequency allele type in the starch metabolic gene, pullulanase, is associated with increased digestibility, regardless of genotypic background. We also provide evidence that the beneficial allele type is not associated with deleterious pleiotropic effects in the modern field environment. We argue that increasing the digestibility of an adapted crop is a viable way forward towards addressing food security while maximizing water and land-use efficiency.

Hyperopic defocus and diurnal changes in human choroid and axial length

Purpose To investigate the influence of monocular hyperopic defocus on the normal diurnal rhythms in axial length and choroidal thickness of young adults. Methods A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained for 15 emmetropic young adults over three consecutive days. The natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular hyperopic defocus (Day 2, – 2.00 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) in diurnal rhythms were examined. Results Both axial length and choroidal thickness underwent significant diurnal changes on each of the three measurement days (p<0.0001). The introduction of monocular hyperopic defocus resulted in significant changes in the diurnal variations observed in both parameters (p<0.05). A significant (p<0.001) increase in the mean amplitude (peak to trough) of change in axial length (mean increase, 0.016 ± 0.005 mm) and choroidal thickness (mean increase, 0.011 ± 0.003 mm) was observed on day 2 with hyperopic defocus compared to the two ‘no defocus’ days (days 1 and 3). At the second measurement (mean time 12:10 pm) on the day with hyperopic defocus, the eye was significantly longer by 0.012 ± 0.002 mm compared to the other two days (p<0.05). No significant difference was observed in the average timing of the daily peaks in axial length (mean peak time 12:12 pm) and choroidal thickness (21:02 pm) over the three days. Conclusions The introduction of monocular hyperopic defocus resulted in a significant increase in the amplitude of the diurnal change in axial length and choroidal thickness that returned to normal the following day after removal of the blur stimulus.

Malnutrition and its impact on cost of hospitalization, length of stay, readmission and 3-year mortality

Background & aims The confounding effect of disease on the outcomes of malnutrition using diagnosis-related groups (DRG) has never been studied in a multidisciplinary setting. This study aims to determine the impact of malnutrition on hospitalisation outcomes, controlling for DRG. Methods Subjective Global Assessment was used to assess the nutritional status of 818 patients within 48 hours of admission. Prospective data were collected on cost of hospitalisation, length of stay (LOS), readmission and mortality up to 3 years post-discharged using National Death Register data. Mixed model analysis and conditional logistic regression matching by DRG were carried out to evaluate the association between nutritional status and outcomes, with the results adjusted for gender, age and race. Results Malnourished patients (29%) had longer hospital stays (6.9±7.3 days vs. 4.6±5.6 days, p<0.001) and were more likely to be readmitted within 15 days (adjusted relative risk = 1.9, 95%CI 1.1–3.2, p=0.025). Within a DRG, the mean difference between actual cost of hospitalisation and the average cost for malnourished patients was greater than well-nourished patients (p=0.014). Mortality was higher in malnourished patients at 1 year (34% vs. 4.1 %), 2 years (42.6% vs. 6.7%) and 3 years (48.5% vs. 9.9%); p<0.001 for all. Overall, malnutrition was a significant predictor of mortality (adjusted hazard ratio = 4.4, 95%CI 3.3-6.0, p<0.001). Conclusions Malnutrition was evident in up to one third of inpatients and led to poor hospitalisation outcomes, even after matching for DRG. Strategies to prevent and treat malnutrition in the hospital and post-discharge are needed.

Queensland’s high risk foot database : tracking the length and width of Queensland’s foot ulcers

Background Foot ulcers are a leading cause of avoidable hospital admissions and lower extremity amputations. However, large clinical studies describing foot ulcer presentations in the ambulatory setting are limited. The aim of this descriptive observational paper is to report the characteristics of ambulatory foot ulcer patients managed across 13 of 17 Queensland Health & Hospital Services. Methods Data on all foot ulcer patients registered with a Queensland High Risk Foot Form (QHRFF) was collected at their first consult in 2012. Data is automatically extracted from each QHRFF into a Queensland high risk foot database. Descriptive statistics display age, sex, ulcer types and co-morbidities. Statewide clinical indicators of foot ulcer management are also reported. Results Overall, 2,034 people presented with a foot ulcer in 2012. Mean age was 63(±14) years and 67.8% were male. Co-morbidities included 85% had diabetes, 49.7% hypertension, 39.2% dyslipidaemia, 25.6% cardiovascular disease, 13.7% kidney disease and 12.2% smoking. Foot ulcer types included 51.6% neuropathic, 17.8% neuro-ischaemic, 7.2% ischaemic, 6.6% post-surgical and 16.8% other; whilst 31% were infected. Clinical indicator results revealed 98% had their wound categorised, 51% received non-removable offloading, median ulcer healing time was 6-weeks and 37% had ulcer recurrence. Conclusion This paper details the largest foot ulcer database reported in Australia. People presenting with foot ulcers appear predominantly older, male with several co-morbidities. Encouragingly it appears most patients are receiving best practice care. These results may be a factor in the significant reduction of Queensland diabetes foot-related hospitalisations and amputations recently reported.

Influence of eye rotation on peripheral eye length measurement obtained with a partial coherence interferometry instrument

Purpose The eye rotation approach for measuring peripheral eye length leads to concern about whether the rotation influences results, such as through pressure exerted by eyelids or extra-ocular muscles. This study investigated whether this approach is valid. Methods Peripheral eye lengths were measured with a Lenstar LS 900 biometer for eye rotation and no-eye rotation conditions (head rotation for horizontal meridian and instrument rotation for vertical meridian). Measurements were made for 23 healthy young adults along the horizontal visual field (±30°) and, for a subset of eight participants along the vertical visual field (±25°). To investigate the influence of the duration of eye rotation, for six participants measurements were made at 0, 60, 120, 180 and 210 s after eye rotation to ±30° along horizontal and vertical visual fields. Results Peripheral eye lengths were not significantly different for the conditions along the vertical meridian (F1,7 = 0.16, p = 0.71). The peripheral eye lengths for the conditions were significantly different along the horizontal meridian (F1,22 = 4.85, p = 0.04), although not at individual positions (p ≥ 0.10) and were not important. There were no apparent differences between the emmetropic and myopic groups. There was no significant change in eye length at any position after maintaining position for 210 s. Conclusion Eye rotation and no-eye rotation conditions were similar for measuring peripheral eye lengths along horizontal and vertical visual field meridians at ±30° and ±25°, respectively. Either condition can be used to estimate retinal shape from peripheral eye lengths.

Putative full-length clones of the genomic DNA segments of subterranean clover stunt virus and identification of the segment coding for the viral coat protein

Subterranean clover stunt disease is an economically important aphid-borne virus disease affecting certain pasture and grain legumes in Australia. The virus associated with the disease, subterranean clover stunt virus (SCSV), was previously found to be representative of a new type of single-stranded DNA virus. Analysis of the virion DNA and restriction mapping of double-stranded cDNA synthesized from virion DNA suggested that SCSV has a segmented genome composed of 3 or 4 different species of circular ssDNA each of about 850-880 nucleotides. To further investigate the complexity of the SCSV genome, we have isolated the replicative form DNA from infected pea and from it prepared putative full-length clones representing the SCSV genome segments. Analysis of these clones by restriction mapping indicated that clones representing at least 4 distinct genomic segments were obtained. This method is thus suitable for generating an extensive genomic library of novel ssDNA viruses containing multiple genome segments such as SCSV and banana bunchy top virus. The N-terminal amino acid sequence and amino acid composition of the coat protein of SCSV were determined. Comparison of the amino acid sequence with partial DNA sequence data, and the distinctly different restriction maps obtained for the full-length clones suggested that only one of these clones contained the coat protein gene. The results confirmed that SCSV has a functionally divided genome composed of several distinct ssDNA circles each of about 1 kb.

Standardising corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy

AIMS: Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy. METHODS: Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy. RESULTS: The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity. CONCLUSIONS: Standardizing corneal nerve fibre length for tortuosity enhances the ability to differentiate individuals with diabetes, with and without neuropathy.

Arm’s length pricing and multinational banks : an old fashioned approach in a modern world

In “Arm’s Length Pricing and Multinational Banks: An Old Fashioned Approach in a Modern World”, Kerrie Sadiq, describes the high level of integration of multinational financial institutions and argues that treating each element within a given operation as a separate entity for transfer pricing purposes is not economically or legally realistic. She proposes instead formulary apportionment as a device for managing this complexity.

Transfer pricing and multinational financial institutions : the case for replacing arm’s length price with a unitary approach

The international tax system, designed a century ago, has not kept pace with the modern multinational entity rendering it ineffective in taxing many modern businesses according to economic activity. One of those modern multinational entities is the multinational financial institution (MNFI). The recent global financial crisis provides a particularly relevant and significant example of the failure of the current system on a global scale. The modern MNFI is increasingly undertaking more globalised and complex trading operations. A primary reason for the globalisation of financial institutions is that they typically ‘follow-the-customer’ into jurisdictions where international capital and international investors are required. The International Monetary Fund (IMF) recently reported that from 1995-2009, foreign bank presence in developing countries grew by 122 per cent. The same study indicates that foreign banks have a 20 per cent market share in OECD countries and 50 per cent in emerging markets and developing countries. Hence, most significant is that fact that MNFIs are increasingly undertaking an intermediary role in developing economies where they are financing core business activities such as mining and tourism. IMF analysis also suggests that in the future, foreign bank expansion will be greatest in emerging economies. The difficulties for developing countries in applying current international tax rules, especially the current traditional transfer pricing regime, are particularly acute in relation to MNFIs, which are the biggest users of tax havens and offshore finance. This paper investigates whether a unitary taxation approach which reflects economic reality would more easily and effectively ensure that the profits of MNFIs are taxed in the jurisdictions which give rise to those profits. It has previously been argued that the uniqueness of MNFIs results in a failure of the current system to accurately allocate profits and that unitary tax as an alternative could provide a sounder allocation model for international tax purposes. This paper goes a step further, and examines the practicalities of the implementation of unitary taxation for MNFIs in terms of the key components of such a regime, along with their their implications. This paper adopts a two-step approach in considering the implications of unitary taxation as a means of improved corporate tax coordination which requires international acceptance and agreement. First, the definitional issues of the unitary MNFI are examined and second, an appropriate allocation formula for this sector is investigated. To achieve this, the paper asks first, how the financial sector should be defined for the purposes of unitary taxation and what should constitute a unitary business for that sector and second, what is the ‘best practice’ model of an allocation formula for the purposes of the apportionment of the profits of the unitary business of a financial institution.

Optimising the length of Random Breath Tests : results from the Queensland Community Engagement Trial

Research suggests that the length and quality of police-citizen encounters affect policing outcomes. The Koper Curve, for example, shows that the optimal length for police presence in hot spots is between 14 and 15 minutes, with diminishing returns observed thereafter. Our study, using data from the Queensland Community Engagement Trial (QCET), examines the impact of encounter length on citizen perceptions of police performance. QCET involved a randomised field trial, where 60 random breath test (RBT) traffic stop operations were randomly allocated to an experimental condition involving a procedurally just encounter or a business-as-usual control condition. Our results show that the optimal length of time for procedurally just encounters during RBT traffic stops is just less than 2 minutes. We show, therefore, that it is important to encourage and facilitate positive police–citizen encounters during RBTat traffic stops, while ensuring that the length of these interactions does not pass a point of diminishing returns.

Estimating hidden message length in binary image embedded by using boundary pixels steganography

In this paper, we propose a new steganalytic method to detect the message hidden in a black and white image using the steganographic technique developed by Liang, Wang and Zhang. Our detection method estimates the length of hidden message embedded in a binary image. Although the hidden message embedded is visually imperceptible, it changes some image statistic (such as inter-pixels correlation). Based on this observation, we first derive the 512 patterns histogram from the boundary pixels as the distinguishing statistic, then we compute the histogram difference to determine the changes of the 512 patterns histogram induced by the embedding operation. Finally we propose histogram quotient to estimate the length of the embedded message. Experimental results confirm that the proposed method can effectively and reliably detect the length of the embedded message.

Short-term changes in axial length during simulations of typical far, intermediate and near tasks

Purpose: To investigate the changes in axial length with the combined effect of accommodation and angle of gaze (convergence and downward gaze) over 5 minutes in groups of myopes and emmetropes. Methods: A total of 31 subjects (nine emmetropes, 10 low myopes, and 12 moderate to high myopes) aged from 18 to 31 years were recruited. To measure ocular biometrics in inferonasal gaze with accommodation, an optical biometer (Lenstar LS900) was inclined on a tilt and height adjustable stage, with the subject’s chinrest mounted on a rotary stage to induce various levels of convergence by rotation of the subject’s head in primary or downward gaze. Initially, the subjects performed a distance viewing task in primary gaze for 10 minutes to provide a ‘wash-out’ period for prior visual tasks, and then the subject’s axial length and ocular biometrics were measured in nine different combinations of gaze/accommodation over 5 minutes. These nine sessions for all gaze measurements (i.e. three levels of accommodation 9 three levels of convergence) were completed across 3 days of testing (one accommodation condition on each day).The nine combinations of gaze/accommodation were based on those required to view the centre, right and left edges of a distant TV at 6 m in primary gaze, an intermediate task (i.e. computer at 50 cm in 10° downward gaze) and a near task (i.e. reading A4 page at 20 cm in 20° downward gaze). Subjects were wearing a custom built three-axes head tracker throughout the experiment that monitored subjects’ relative head movements (roll, pitch and yaw) during measurements. Results: A significant increase in axial length occurred with the combined effect of accommodation, convergence and downward gaze (repeated measures ANOVA, p < 0.001), with the greatest axial elongation during the near task in downward gaze with convergence (i.e. downward 20°/inward 33°, with 5 D accommodation) (mean change 33 ± 13 lm, after 5 minutes task) followed by the intermediate task (i.e. downward 10°/inward 25°, with 2 D accommodation) (mean change 14 ± 11 lm, after 5 minutes task).Changes in axial length for the distance task (i.e. primary gaze/9° convergence, with 0.16 D accommodation) were not statistically significant (mean change 4 ± 8 lm, after 5 minutes task, p > 0.05). Moderate to high myopes had a greater change in the axial length (mean change 40 ± 11 lm after 5 minutes of near task) than that of emmetropes (mean change 29 ± 15 lm after 5 minutes of near task) and low myopes (mean change 29 ± 16 lm after 5 minutes of near task) associated with time (p = 0.02) and accommodation by time (p = 0.03). Conclusions: The combination of accommodation, convergence and downward angle has a significant short term effect on axial length over time. The near task in downward gaze with convergence caused a greater change in axial length than the intermediate and distant visual tasks. The greater axial elongation measured in the infero-nasal direction with accommodation is most likely associated with a combination of biomechanical factors such as, extraocular muscle forces and ciliary muscle contraction.

Survival models of community tenure and length of hospital stay for the seriously mentally ill : a 10-year perspective

Objective: To examine the effects of personal and community characteristics, specifically race and rurality, on lengths of state psychiatric hospital and community stays using maximum likelihood survival analysis with a special emphasis on change over a ten year period of time. Data Sources: We used the administrative data of the Virginia Department of Mental Health, Mental Retardation, and Substance Abuse Services (DMHMRSAS) from 1982-1991 and the Area Resources File (ARF). Given these two sources, we constructed a history file for each individual who entered the state psychiatric system over the ten year period. Histories included demographic, treatment, and community characteristics. Study Design: We used a longitudinal, population-based design with maximum likelihood estimation of survival models. We presented a random effects model with unobserved heterogeneity that was independent of observed covariates. The key dependent variables were lengths of inpatient stay and subsequent length of community stay. Explanatory variables measured personal, diagnostic, and community characteristics, as well as controls for calendar time. Data Collection: This study used secondary, administrative, and health planning data. Principal Findings: African-American clients leave the community more quickly than whites. After controlling for other characteristics, however, race does not affect hospital length of stay. Rurality does not affect length of community stays once other personal and community characteristics are controlled for. However, people from rural areas have longer hospital stays even after controlling for personal and community characteristics. The effects of time are significantly smaller than expected. Diagnostic composition effects and a decrease in the rate of first inpatient admissions explain part of this reduced impact of time. We also find strong evidence for the existence of unobserved heterogeneity in both types of stays and adjust for this in our final models. Conclusions: Our results show that information on client characteristics available from inpatient stay records is useful in predicting not only the length of inpatient stay but also the length of the subsequent community stay. This information can be used to target increased discharge planning for those at risk of more rapid readmission to inpatient care. Correlation across observed and unobserved factors affecting length of stay has significant effects on the measurement of relationships between individual factors and lengths of stay. Thus, it is important to control for both observed and unobserved factors in estimation.