Losing the ability in activities of daily living in the oldest old: a hierarchic disability scale from the Newcastle 85+ study

Objectives

To investigate the order in which 85 year olds develop difficulty in performing a wide range of daily activities covering basic personal care, household care and mobility.

Design

Cross-sectional analysis of baseline data from a cohort study.

Setting

Newcastle upon Tyne and North Tyneside, UK.

Participants

Individuals born in 1921, registered with participating general practices.

Measurements

Detailed health assessment including 17 activities of daily living related to basic personal care, household care and mobility. Questions were of the form ‘Can you …’ rather than ‘Do you…’ Principal Component Analysis (PCA) was used to confirm a single underlying dimension for the items and Mokken Scaling was used to determine a subsequent hierarchy. Validity of the hierarchical scale was assessed by its associations with known predictors of disability.

Results

839 people within the Newcastle 85+ study for whom complete information was available on self-reported Activities of Daily Living (ADL). PCA confirmed a single underlying dimension; Mokken scaling confirmed a hierarchic scale where ‘Cutting toenails’ was the first item with which participants had difficulty and ‘feeding’ the last. The ordering of loss differed between men and women. Difficulty with ‘shopping’ and ‘heavy housework’ were reported earlier by women whilst men reported ‘walking 400 yards’ earlier. Items formed clusters corresponding to strength, balance, lower and upper body involvement and domains specifically required for balance and upper/lower limb functional integrity.

Conclusion

This comprehensive investigation of ordering of ability in activities in 85 year olds will inform researchers and practitioners assessing older people for onset of disability and subsequent care needs.     

Sub-typing of rheumatic diseases based on a systems diagnosis questionnaire

Background

The future of personalized medicine depends on advanced diagnostic tools to characterize responders and non-responders to treatment. Systems diagnosis is a new approach which aims to capture a large amount of symptom information from patients to characterize relevant sub-groups.

Methodology

49 patients with a rheumatic disease were characterized using a systems diagnosis questionnaire containing 106 questions based on Chinese and Western medicine symptoms. Categorical principal component analysis (CATPCA) was used to discover differences in symptom patterns between the patients. Two Chinese medicine experts where subsequently asked to rank the Cold and Heat status of all the patients based on the questionnaires. These rankings were used to study the Cold and Heat symptoms used by these practitioners.

Findings

The CATPCA analysis results in three dimensions. The first dimension is a general factor (40.2% explained variance). In the second dimension (12.5% explained variance) ‘anxious’, ‘worrying’, ‘uneasy feeling’ and ‘distressed’ were interpreted as the Internal disease stage, and ‘aggravate in wind’, ‘fear of wind’ and ‘aversion to cold’ as the External disease stage. In the third dimension (10.4% explained variance) ‘panting s’, ‘superficial breathing’, ‘shortness of breath s’, ‘shortness of breath f’ and ‘aversion to cold’ were interpreted as Cold and ‘restless’, ‘nervous’, ‘warm feeling’, ‘dry mouth s’ and ‘thirst’ as Heat related. ‘Aversion to cold’, ‘fear of wind’ and ‘pain aggravates with cold’ are most related to the experts Cold rankings and ‘aversion to heat’, ‘fullness of chest’ and ‘dry mouth’ to the Heat rankings.

Conclusions

This study shows that the presented systems diagnosis questionnaire is able to identify groups of symptoms that are relevant for sub-typing patients with a rheumatic disease.     

Development and Validation of the Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) for Primary Care Patients with Type 2 Diabetes

Objectives

To develop and evaluate the psychometric properties of a Chinese questionnaire which assesses the barriers and enablers to commencing insulin in primary care patients with poorly controlled Type 2 diabetes.

Research Design and Method

Questionnaire items were identified using literature review. Content validation was performed and items were further refined using an expert panel. Following translation, back translation and cognitive debriefing, the translated Chinese questionnaire was piloted on target patients. Exploratory factor analysis and item-scale correlations were performed to test the construct validity of the subscales and items. Internal reliability was tested by Cronbach’s alpha.

Results

Twenty-seven identified items underwent content validation, translation and cognitive debriefing. The translated questionnaire was piloted on 303 insulin naïve (never taken insulin) Type 2 diabetes patients recruited from 10 government-funded primary care clinics across Hong Kong. Sufficient variability in the dataset for factor analysis was confirmed by Bartlett’s Test of Sphericity (P<0.001). Using exploratory factor analysis with varimax rotation, 10 factors were generated onto which 26 items loaded with loading scores > 0.4 and Eigenvalues >1. Total variance for the 10 factors was 66.22%. Kaiser-Meyer-Olkin measure was 0.725. Cronbach’s alpha coefficients for the first four factors were ≥0.6 identifying four sub-scales to which 13 items correlated. Remaining sub-scales and items with poor internal reliability were deleted. The final 13-item instrument had a four scale structure addressing: ‘Self-image and stigmatization’; ‘Factors promoting self-efficacy; ‘Fear of pain or needles’; and ‘Time and family support’.

Conclusion

The Chinese Attitudes to Starting Insulin Questionnaire (Ch-ASIQ) appears to be a reliable and valid measure for assessing barriers to starting insulin. This short instrument is easy to administer and may be used by healthcare providers and researchers as an assessment tool for Chinese diabetic primary care patients, including the elderly, who are unwilling to start insulin.     

Graduate entry medicine: selection criteria and student performance

Background

Graduate entry medicine raises new questions about the suitability of students with different backgrounds. We examine this, and the broader issue of effectiveness of selection and assessment procedures.

Methods

The data included background characteristics, academic record, interview score and performance in pre-clinical modular assessment for two years intake of graduate entry medical students. Exploratory factor analysis is a powerful method for reducing a large number of measures to a smaller group of underlying factors. It was used here to identify patterns within and between the selection and performance data.

Principal Findings

Basic background characteristics were of little importance in predicting exam success. However, easily interpreted components were detected within variables comprising the ‘selection’ and ‘assessment’ criteria. Three selection components were identified (‘Academic’, ‘GAMSAT’, ‘Interview’) and four assessment components (‘General Exam’, ‘Oncology’, ‘OSCE’, ‘Family Case Study’). There was a striking lack of relationships between most selection and performance factors. Only ‘General Exam’ and ‘Academic’ showed a correlation (Pearson''s r = 0.55, p<0.001).

Conclusions

This study raises questions about methods of student selection and their effectiveness in predicting performance and assessing suitability for a medical career. Admissions tests and most exams only confirmed previous academic achievement, while interview scores were not correlated with any consequent assessment.     

Coding, recording and incidence of different forms of coronary heart disease in primary care

Objectives

To evaluate the coding, recording and incidence of coronary heart disease (CHD) in primary care electronic medical records.

Methods

Data were drawn from the UK General Practice Research Database. Analyses evaluated the occurrence of 271 READ medical diagnostic codes, including categories for ‘Angina’, ‘Myocardial Infarction’, ‘Coronary Artery Bypass Grafting’ (CABG), ‘percutaneous transluminal coronary angioplasty’ (PCTA) and ‘Other Coronary Heart Disease’. Time-to-event analyses were implemented to evaluate occurrences of different groups of codes after the index date.

Results

Among 300,020 participants aged greater than 30 years there were 75,197 unique occurrences of coronary heart disease codes in 24,244 participants, with 12,495 codes for incident events and 62,702 for prevalent events. Among incident event codes, 3,607 (28.87%) were for angina, 3,262 (26.11%) were for MI, 514 (4.11%) for PCTA, 161 (1.29%) for CABG and 4,951 (39.62%) were for ‘Other CHD’. Among prevalent codes, 20,254 (32.30%) were for angina, 3,644 (5.81%) for MI, 34,542 (55.09%) for ‘Other CHD’ and 4,262 (6.80%) for CABG or PCTA. Among 3,685 participants initially diagnosed exclusively with ‘Other CHD’ codes, 17.1% were recorded with angina within 5 years, 5.6% with myocardial infarction, 6.3% with CABG and 8.6% with PCTA. From 2000 to 2010, the overall incidence of CHD declined, as did the incidence of angina, but the incidence of MI did not change. The frequency of CABG declined, while PCTA increased.

Conclusion

In primary care electronic records, a substantial proportion of coronary heart disease events are recorded with codes that do not distinguish between different clinical presentations of CHD. The results draw attention to the need to improve coding practice in primary care. The results also draw attention to the importance of code selection in research studies and the need for sensitivity analyses using different sets of codes.     

The Association of Longitudinal and Interpersonal Continuity of Care with Emergency Department Use,Hospitalization, and Mortality among Medicare Beneficiaries

Background

Continuity of medical care is widely believed to lead to better health outcomes and service utilization patterns for patients. Most continuity studies, however, have only used administrative claims to assess longitudinal continuity with a provider. As a result, little is known about how interpersonal continuity (the patient''s experience at the visit) relates to improved health outcomes and service use.

Methods

We linked claims-based longitudinal continuity and survey-based self-reported interpersonal continuity indicators for 1,219 Medicare beneficiaries who completed the National Health and Health Services Use Questionnaire. With these linked data, we prospectively evaluated the effect of both types of continuity of care indicators on emergency department use, hospitalization, and mortality over a five-year period.

Results

Patient-reported continuity was associated with reduced emergency department use, preventable hospitalization, and mortality. Most of the claims-based measures, including those most frequently used to assess continuity, were not associated with reduced utilization or mortality.

Conclusion

Our results indicate that the patient- and claims-based indicators of continuity have very different effects on these important health outcomes, suggesting that reform efforts must include the patient-provider experience when evaluating health care quality.     

Source of previous treatment for re-treatment TB cases registered under the National TB control Programme, India, 2010

Background

In 2009, nearly half (289,756) of global re-treatment TB notifications are from India; no nationally-representative data on the source of previous treatment was available to inform strategies for improvement of initial TB treatment outcome.

Objectives

To assess the source of previous treatment for re-treatment TB patients registered under India''s Revised National TB control Programme (RNTCP).

Methodology

A nationally-representative cross sectional study was conducted in a sample of 36 randomly-selected districts. All consecutively registered retreatment TB patients during a defined 15-day period in these 36 districts were contacted and the information on the source of previous treatment sought.

Results

Data was collected from all 1712 retreatment TB patients registered in the identified districts during the study period. The data includes information on 595 ‘relapse’ cases, 105 ‘failure’ cases, 437 ‘treatment after default (TAD)’ cases and 575 ‘re-treatment others’ cases. The source of most recent previous anti-tuberculosis therapy for 754 [44% (95% CI, 38.2%–49.9%)] of the re-treatment TB patients was from providers outside the TB control programme. A higher proportion of patients registered as TAD (64%) and ‘retreatment others’ (59%) were likely to be treated outside the National Programme, when compared to the proportion among ‘relapse’ (22%) or ‘failure’ (6%). Extrapolated to national registration, of the 292,972 re-treatment registrations in 2010, 128,907 patients would have been most recently treated outside the national programme.

Conclusions

Nearly half of the re-treatment cases registered with the national programme were most recently treated outside the programme setting. Enhanced efforts towards extending treatment support and supervision to patients treated by private sector treatment providers are urgently required to improve the quality of treatment and reduce the numbers of patients with recurrent disease. In addition, reasons for the large number of recurrent TB cases from those already treated by the national programme require urgent detailed investigation.     

Relationships between xylem vessel characteristics, calculated axial hydraulic conductance and size-controlling capacity of peach rootstocks

Background and Aims

Previous studies indicate that the size-controlling capacity of peach rootstocks is associated with reductions of scion water potential during mid-day that are caused by the reduced hydraulic conductance of the rootstock. Thus, shoot growth appears to be reduced by decreases in stem water potential. The aim of this study was to investigate the mechanism of reduced hydraulic conductance in size-controlling peach rootstocks.

Methods

Anatomical measurements (diameter and frequency) of xylem vessels were determined in shoots, trunks and roots of three contrasting peach rootstocks grown as trees, each with different size-controlling characteristics: ‘Nemaguard’ (vigorous), ‘P30-135’ (intermediate vigour) and ‘K146-43’ (substantially dwarfing). Based on anatomical measurements, the theoretical axial xylem conductance of each tissue type and rootstock genotype was calculated via the Poiseuille–Hagen law.

Key Results

Larger vessel dimensions were found in the vigorous rootstock (‘Nemaguard’) than in the most dwarfing one (‘K146-43’) whereas vessels of ‘P30-135’ had intermediate dimensions. The density of vessels per xylem area in ‘Nemaguard’ was also less than in ‘P30-135’and ‘K146-43’. These characteristics resulted in different estimated hydraulic conductance among rootstocks: ‘Nemaguard’ had higher theoretical values followed by ‘P30-135’ and ‘K146-43’.

Conclusions

These data indicate that phenotypic differences in xylem anatomical characteristics of rootstock genotypes appear to influence hydraulic conductance capacity directly, and therefore may be the main determinant of dwarfing in these peach rootstocks.Key words: Prunus, rootstock, vessel diameter, hydraulic conductance, dwarfing, xylem anatomy, Poiseuille–Hagen     

The infection processes of Sclerotinia sclerotiorum in cotyledon tissue of a resistant and a susceptible genotype of Brassica napus

Background and Aims

Sclerotinia sclerotiorum can attack >400 plant species worldwide. Very few studies have investigated host–pathogen interactions at the plant surface and cellular level in resistant genotypes of oilseed rape/canola (Brassica napus).

Methods

Infection processes of S. sclerotiorum were examined on two B. napus genotypes, one resistant cultivar ‘Charlton’ and one susceptible ‘RQ001-02M2’ by light and scanning electron microscopy from 2 h to 8 d post-inoculation (dpi).

Key Results

The resistant ‘Charlton’ impeded fungal growth at 1, 2 and 3 dpi, suppressed formation of appresoria and infection cushions, caused extrusion of protoplast from hyphal cells and produced a hypersensitive reaction. At 8 dpi, whilst in ‘Charlton’ pathogen invasion was mainly confined to the upper epidermis, in the susceptible ‘RQ001-02M2’, colonization up to the spongy mesophyll cells was evident. Calcium oxalate crystals were found in the upper epidermis and in palisade cells in susceptible ‘RQ001-02M2’ at 6 dpi, and throughout leaf tissues at 8 dpi. In resistant ‘Charlton’, crystals were not observed at 6 dpi, whereas at 8 dpi they were mainly confined to the upper epidermis. Starch deposits were also more prevalent in ‘RQ001-02M2’.

Conclusions

This study demonstrates for the first time at the cellular level that resistance to S. sclerotiorum in B. napus is a result of retardation of pathogen development, both on the plant surface and within host tissues. The resistance mechanisms identified in this study will be useful for engineering disease-resistant genotypes and for developing markers for screening for resistance against this pathogen.     

Coverage and Quality of Antenatal Care Provided at Primary Health Care Facilities in the ‘Punjab’ Province of ‘Pakistan’

Background

Antenatal care is a very important component of maternal health services. It provides the opportunity to learn about risks associated with pregnancy and guides to plan the place of deliveries thereby preventing maternal and infant morbidity and mortality. In ‘Pakistan’ antenatal services to rural population are being provided through a network of primary health care facilities designated as ''Basic Health Units and Rural Health Centers. Pakistan is a developing country, consisting of four provinces and federally administered areas. Each province is administratively subdivided in to ‘Divisions’ and ‘Districts’. By population ‘Punjab’ is the largest province of Pakistan having 36 districts. This study was conducted to assess the coverage and quality antenatal care in the primary health care facilities in ‘Punjab’ province of ‘Pakistan’.

Methods

Quantitative and Qualitative methods were used to collect data. Using multistage sampling technique nine out of thirty six districts were selected and 19 primary health care facilities of public sector (seventeen Basic Health Units and two Rural Health Centers were randomly selected from each district. Focus group discussions and in-depth interviews were conducted with clients, providers and health managers.

Results

The overall enrollment for antenatal checkup was 55.9% and drop out was 32.9% in subsequent visits. The quality of services regarding assessment, treatment and counseling was extremely poor. The reasons for low coverage and quality were the distant location of facilities, deficiency of facility resources, indifferent attitude and non availability of the staff. Moreover, lack of client awareness about importance of antenatal care and self empowerment for decision making to seek care were also responsible for low coverage.

Conclusion

The coverage and quality of the antenatal care services in ‘Punjab’ are extremely compromised. Only half of the expected pregnancies are enrolled and out of those 1/3 drop out in follow-up visits.     

Distinct mechanisms for aerenchyma formation in leaf sheaths of rice genotypes displaying a quiescence or escape strategy for flooding tolerance

Background and Aims

Rice is one of the few crops able to withstand periods of partial or even complete submergence. One of the adaptive traits of rice is the constitutive presence and further development of aerenchyma which enables oxygen to be transported to submerged organs. The development of lysigenous aerenchyma is promoted by ethylene accumulating within the submerged plant tissues, although other signalling mechanisms may also co-exist. In this study, aerenchyma development was analysed in two rice (Oryza sativa) varieties, ‘FR13A’ and ‘Arborio Precoce’, which show opposite traits in flooding response in terms of internode elongation and survival.

Methods

The growth and survival of rice varieties under submergence was investigated in the leaf sheath of ‘FR13A’ and ‘Arborio Precoce’. The possible involvement of ethylene and reactive oxygen species (ROS) was evaluated in relation to aerenchyma formation. Cell viability and DNA fragmentation were determined by FDA/FM4-64 staining and TUNEL assay, respectively. Ethylene production was monitored by gas chromatography and by analysing ACO gene expression. ROS production was measured by using Amplex Red assay kit and the fluorescent dye DCFH₂-DA. The expression of APX1 was also evaluated. AVG and DPI solutions were used to test the effect of inhibiting ethylene biosynthesis and ROS production, respectively.

Key Results

Both the varieties displayed constitutive lysigenous aerenchyma formation, which was further enhanced when submerged. ‘Arborio Precoce’, which is characterized by fast elongation when submerged, showed active ethylene biosynthetic machinery associated with increased aerenchymatous areas. ‘FR13A’, which harbours the Sub1A gene that limits growth during oxygen deprivation, did not show any increase in ethylene production after submersion but still displayed increased aerenchyma. Hydrogen peroxide levels increased in ‘FR13A’ but not in ‘Arborio Precoce’.

Conclusions

While ethylene controls aerenchyma formation in the fast-elongating ‘Arborio Precoce’ variety, in ‘FR13A’ ROS accumulation plays an important role.     

Maternal malaria, birth size and blood pressure in Nigerian newborns: insights into the developmental origins of hypertension from the Ibadan growth cohort

Background

Hypertension is an increasing health issue in sub-Saharan Africa where malaria remains common in pregnancy. We established a birth cohort in Nigeria to evaluate the early impact of maternal malaria on newborn blood pressure (BP).

Methods

Anthropometric measurements, BP, blood films for malaria parasites and haematocrit were obtained in 436 mother-baby pairs. Women were grouped to distinguish between the timing of malaria parasitaemia as ‘No Malaria’, ‘Malaria during pregnancy only’ or ‘Malaria at delivery’, and parasite density as low (<1000 parasites/µl of blood) and high (≥1000/µl).

Results

Prevalence of maternal malaria parasitaemia was 48%, associated with younger maternal age (p<0.001), being primigravid (p = 0.022), lower haematocrit (p = 0.028). High parasite density through pregnancy had the largest effect on mean birth indices so that weight, length, head and mid-upper arm circumferences were smaller by 300 g, 1.1 cm, 0.7 cm and 0.4 cm respectively compared with ‘No malaria’ (all p≤0.005). In babies of mothers who had ‘malaria at delivery’, their SBPs adjusted for other confounders were lower respectively by 4.3 and 5.7 mmHg/kg compared with ‘malaria during pregnancy only’ or ‘none’. In contrast the mean newborn systolic (SBP) and diastolic BPs (DBP) adjusted for birth weight were higher by 1.7 and 1.4 mmHg/kg respectively in babies whose mothers had high compared with low parasitaemia.

Conclusions

As expected, prenatal malarial exposure had a significant impact on fetal growth rates. Malaria at delivery was associated with the lowest newborn BPs while malaria through pregnancy, which may attenuate growth of the vascular network, generated higher newborn BPs adjusted for size. These neonatal findings have potential implications for cardiovascular health in sub-Saharan Africa.     

Foundation characteristics of edible Musa triploids revealed from allelic distribution of SSR markers

Background and Aims

The production of triploid banana and plantain (Musa spp.) cultivars with improved characteristics (e.g. greater disease resistance or higher yield), while still preserving the main features of current popular cultivars (e.g. taste and cooking quality), remains a major challenge for Musa breeders. In this regard, breeders require a sound knowledge of the lineage of the current sterile triploid cultivars, to select diploid parents that are able to transmit desirable traits, together with a breeding strategy ensuring final triploidization and sterility. Highly polymorphic single sequence repeats (SSRs) are valuable markers for investigating phylogenetic relationships.

Methods

Here, the allelic distribution of each of 22 SSR loci across 561 Musa accessions is analysed.

Key Results and Conclusions

We determine the closest diploid progenitors of the triploid ‘Cavendish’ and ‘Gros Michel’ subgroups, valuable information for breeding programmes. Nevertheless, in establishing the likely monoclonal origin of the main edible triploid banana subgroups (i.e. ‘Cavendish’, ‘Plantain’ and ‘Mutika-Lujugira’), we postulated that the huge phenotypic diversity observed within these subgroups did not result from gamete recombination, but rather from epigenetic regulations. This emphasizes the need to investigate the regulatory mechanisms of genome expression on a unique model in the plant kingdom. We also propose experimental standards to compare additional and independent genotyping data for reference.     

From Where Are Tuberculosis Patients Accessing Treatment in India? Results from a Cross-Sectional Community Based Survey of 30 Districts

Background

Tuberculosis (TB) notification in India by the Revised National TB Control Programme (RNTCP) provides information on TB patients registered for treatment from the programme. There is limited information about the proportion of patients treated for TB outside RNTCP and where these patients access their treatment.

Objectives

To estimate the proportion of patients accessing TB treatment outside the RNTCP and to identify their basic demographic characteristics.

Methods

A cross sectional community-based survey in 30 districts. Patients were identified through a door-to-door survey and interviewed using a semi-structured questionnaire.

Results

Of the estimated 75,000 households enumerated, 73,249 households (97.6%) were visited. Of the 371,174 household members, 761 TB patients were identified (∼205 cases per 100,000 populations). Data were collected from 609 (80%) TB patients of which 331 [54% (95% CI: 42–66%)] were determined to be taking treatment ‘under DOTS/RNTCP’. The remaining 278 [46% (95% CI: 34–57%)] were on treatment from ‘outside DOTS/RNTCP’ sources and hence were unlikely to be part of the TB notification system. Patients who were accessing treatment from ‘outside DOTS/RNTCP’ were more likely to be patients from rural areas [adjusted Odds Ratio (aOR) 2.5, 95% CI (1.2–5.3)] and whose TB was diagnosed in a non-government health facility (aOR 14.0, 95% CI 7.9–24.9).

Conclusions

This community-based survey found that nearly half of self-reported TB patients were missed by TB notification system in these districts. The study highlights the need for 1) Reviewing and revising the scope of the TB notification system, 2) Strengthening and monitoring health care delivery systems with periodic assessment of the reach and utilisation of the RNTCP services especially among rural communities, 3) Advocacy, communication and social mobilisation activities focused at rural communities with low household incomes and 4) Inclusive involvement of all health-care providers, especially providers of poor rural communities.     

Hubs with network motifs organize modularity dynamically in the protein-protein interaction network of yeast

Background

It has been recognized that modular organization pervades biological complexity. Based on network analysis, ‘party hubs’ and ‘date hubs’ were proposed to understand the basic principle of module organization of biomolecular networks. However, recent study on hubs has suggested that there is no clear evidence for coexistence of ‘party hubs’ and ‘date hubs’. Thus, an open question has been raised as to whether or not ‘party hubs’ and ‘date hubs’ truly exist in yeast interactome.

Methodology

In contrast to previous studies focusing on the partners of a hub or the individual proteins around the hub, our work aims to study the network motifs of a hub or interactions among individual proteins including the hub and its neighbors. Depending on the relationship between a hub''s network motifs and protein complexes, we define two new types of hubs, ‘motif party hubs’ and ‘motif date hubs’, which have the same characteristics as the original ‘party hubs’ and ‘date hubs’ respectively. The network motifs of these two types of hubs display significantly different features in spatial distribution (or cellular localizations), co-expression in microarray data, controlling topological structure of network, and organizing modularity.

Conclusion

By virtue of network motifs, we basically solved the open question about ‘party hubs’ and ‘date hubs’ which was raised by previous studies. Specifically, at the level of network motifs instead of individual proteins, we found two types of hubs, motif party hubs (mPHs) and motif date hubs (mDHs), whose network motifs display distinct characteristics on biological functions. In addition, in this paper we studied network motifs from a different viewpoint. That is, we show that a network motif should not be merely considered as an interaction pattern but be considered as an essential function unit in organizing modules of networks.     

A quick mind with letters can be a slow mind with natural scenes: individual differences in attentional selection

Background

Most people show a remarkable deficit in reporting the second of two targets (T2) when presented 200–500 ms after the first (T1), reflecting an ‘attentional blink’ (AB). However, there are large individual differences in the magnitude of the effect, with some people, referred to as ‘non-blinkers’, showing no such attentional restrictions.

Methodology/Principal Findings

Here we replicate these individual differences in a task requiring identification of two letters amongst digits, and show that the observed differences in T2 performance cannot be attributed to individual differences in T1 performance. In a second experiment, the generality of the non-blinkers'' superior performance was tested using a task containing novel pictures rather than alphanumeric stimuli. A substantial AB was obtained in non-blinkers that was equivalent to that of ‘blinkers’.

Conclusion/Significance

The results suggest that non-blinkers employ an efficient target selection strategy that relies on well-learned alphabetic and numeric category sets.     

Preventing nerve function impairment in leprosy: validation and updating of a prediction rule

Background

To validate and update a prediction rule for estimating the risk of leprosy-related nerve function impairment (NFI).

Methodology/Principal Findings

Prospective cohort using routinely collected data, in which we determined the discriminative ability of a previously published rule and an updated rule with a concordance statistic (c). Additional risk factors were analyzed with a Cox proportional hazards regression model. The population consisted of 1,037 leprosy patients newly diagnosed between 2002 and 2003 in the health care facilities of the Rural Health Program in Nilphamari and Rangpur districts in northwest Bangladesh. The primary outcome was the time until the start of treatment. An NFI event was defined as the decision to treat NFI with corticosteroids after diagnosis. NFI occurred in 115 patients (13%; 95% confidence interval 11%–16%). The original prediction rule had adequate discriminative ability (c = 0.79), but could be improved by substituting one predicting variable: ‘long-standing nerve function impairment at diagnosis’ by ‘anti-PGL-I antibodies’. The adjusted prediction rule was slightly better (c = 0.81) and identified more patients with NFI (80%) than the original prediction rule (72%).

Conclusions/Significance

NFI can well be predicted by using the risk variables ‘leprosy classification’ and ‘anti-PGL-I antibodies’. The use of these two variables that do not include NFI offer the possibility of predicting NFI, even before it occurs for the first time. Surveillance beyond the treatment period can be targeted to those most likely to benefit from preventing permanent disabilities.     

Phenotypic complexity, measurement bias, and poor phenotypic resolution contribute to the missing heritability problem in genetic association studies

Background

The variance explained by genetic variants as identified in (genome-wide) genetic association studies is typically small compared to family-based heritability estimates. Explanations of this ‘missing heritability’ have been mainly genetic, such as genetic heterogeneity and complex (epi-)genetic mechanisms.

Methodology

We used comprehensive simulation studies to show that three phenotypic measurement issues also provide viable explanations of the missing heritability: phenotypic complexity, measurement bias, and phenotypic resolution. We identify the circumstances in which the use of phenotypic sum-scores and the presence of measurement bias lower the power to detect genetic variants. In addition, we show how the differential resolution of psychometric instruments (i.e., whether the instrument includes items that resolve individual differences in the normal range or in the clinical range of a phenotype) affects the power to detect genetic variants.

Conclusion

We conclude that careful phenotypic data modelling can improve the genetic signal, and thus the statistical power to identify genetic variants by 20–99%.     

Genotypic differences in pod wall and seed growth relate to invertase activities and assimilate transport pathways in asparagus bean

Background and Aims

Coordination of sugar transport and metabolism between developing seeds and their enclosing fruit tissues is little understood. In this study the physiological mechanism is examined using two genotypes of asparagus bean (Vigna unguiculata ssp. sesquipedialis) differing in pod wall and seed growth rates. Pod growth dominates over seed growth in genotype ‘Zhijiang 121’ but not in ‘Zhijiang 282’ in which a ‘bulging pod’ phenotype is apparent from 8 d post-anthesis (dpa) onward.

Methods

Seed and pod wall growth rates and degree of pod-bulging were measured in the two genotypes together with assays of activities of sucrose-degrading enzymes and sugar content in pod wall and seed and evaluation of cellular pathways of phloem unloading in seed coat using a symplasmic fluorescent dye, 5(6)-carboxyfluorescein (CF).

Key Results

Activities of cell wall, cytoplasmic and vacuolar invertases (CWIN, CIN and VIN) were significantly smaller in pod walls of ‘282’ than in ‘121’ at 10 dpa onwards. Low INV activities were associated with weak pod wall growth of ‘282’. In seed coats, CF was confined within the vasculature in ‘282’ but moved beyond the vasculature in ‘121’, indicating apoplasmic and symplasmic phloem unloading, respectively. Higher CWIN activity in ‘282’ seed coats at 6–8 dpa correlated with high hexose concentration in embryos and enhanced early seed growth. However, CWIN activity in ‘282’ decreased significantly compared with ‘121’ from 10 dpa onwards, coinciding with earlier commencement of nuclei endoreduplication in their embryos.

Conclusions

The study shows genotypic differences between ‘bulging pod’ and ‘non-bulging’ phenotypes of asparagus bean in sucrose metabolism in relation to the pathway of phloem unloading in developing seed coats, and to pod and seed growth. Low INV activity in pod wall corresponds to its shortened and weak growth period; by contrast, the apoplasmic path in the seed coat is associated with high CWIN activity and strong early seed growth.     

Genotypic differences in Al resistance and the role of cell-wall pectin in Al exclusion from the root apex in Fagopyrum tataricum

Background and Aims

Aluminium (Al) toxicity is one of the factors limiting crop production on acid soils. However, genotypic differences exist among plant species or cultivars in response to Al toxicity. This study aims to investigate genotypic differences among eight cultivars of tatary buckwheat (Fagopyrum tataricum) for Al resistance and explore the possible mechanisms of Al resistance.

Methods

Al resistance was evaluated based on relative root elongation (root elongation with Al/root elongation without Al). Root apex Al content, pectin content and exudation of root organic acids were determined and compared.

Key Results

Genotypic differences among the eight cultivars were correlated with exclusion of Al from the root apex. However, there was a lack of correlation between Al exclusion and Al-induced oxalate secretion. Interestingly, cell-wall pectin content of the root apex was generally lower in Al-resistant cultivars than in Al-sensitive cultivars. Although we were unable to establish a significant correlation between Al exclusion and pectin content among the eight cultivars, a strong correlation could be established among six cultivars, in which the pectin content in the most Al-resistant cultivar ‘Chuan’ was significantly lower than that in the most Al-sensitive cultivar ‘Liuku2’. Furthermore, root apex cell-wall pectin methylesterase activity (PME) was similar in ‘Chuan’ and ‘Liuku2’ in the absence of Al, but Al treatment resulted in increased PME activity in ‘Liuku2’ compared with ‘Chuan’. Immunolocalization of pectins also showed that the two cultivars had similar amounts of either low-methyl-ester pectins or high-methyl-ester pectins in the absence of Al, but Al treatment resulted in a more significant increase of low-methyl-ester pectins and decrease of high-methyl-ester pectins in ‘Liuku2’.

Conclusions

Cell-wall pectin content may contribute, at least in part, to differential Al resistance among tatary buckwheat cultivars.