A major QTL corresponding to the Rk locus for resistance to root-knot nematodes in cowpea (Vigna unguiculata L. Walp.).

Key messageGenome resolution of a major QTL associated with the Rk locus in cowpea for resistance to root-knot nematodes has significance for plant breeding programs and R gene characterization. Cowpea (Vigna unguiculata L. Walp.) is a susceptible host of root-knot nematodes (Meloidogyne spp.) (RKN), major plant-parasitic pests in global agriculture. To date, breeding for host resistance in cowpea has relied on phenotypic selection which requires time-consuming and expensive controlled infection assays. To facilitate marker-based selection, we aimed to identify and map quantitative trait loci (QTL) conferring the resistance trait. One recombinant inbred line (RIL) and two F2:3 populations, each derived from a cross between a susceptible and a resistant parent, were genotyped with genome-wide single nucleotide polymorphism (SNP) markers. The populations were screened in the field for root-galling symptoms and/or under growth-chamber conditions for nematode reproduction levels using M. incognita and M. javanica biotypes. One major QTL was mapped consistently on linkage group VuLG11 of each population. By genotyping additional cowpea lines and near-isogenic lines derived from conventional backcrossing, we confirmed that the detected QTL co-localized with the genome region associated with the Rk locus for RKN resistance that has been used in conventional breeding for many decades. This chromosomal location defined with flanking markers will be a valuable target in marker-assisted breeding and for positional cloning of genes controlling RKN resistance

A Novel Root-Knot Nematode Resistance QTL on Chromosome Vu01 in Cowpea.

The root-knot nematode (RKN) species Meloidogyne incognita and M. javanica cause substantial root system damage and suppress yield of susceptible cowpea cultivars. The narrow-based genetic resistance conferred by the Rk gene, present in some commercial cultivars, is not effective against Rk-virulent populations found in several cowpea production areas. The dynamics of virulence within RKN populations require a broadening of the genetic base of resistance in elite cowpea cultivars. As part of this goal, F1 and F2 populations from the cross CB46-Null (susceptible) x FN-2-9-04 (resistant) were phenotyped for M. javanica induced root-galling (RG) and egg-mass production (EM) in controlled growth chamber and greenhouse infection assays. In addition, F[Formula: see text] families of the same cross were phenotyped for RG on field sites infested with Rk-avirulent M. incognita and M. javanica The response of F1 to RG and EM indicated that resistance to RKN in FN-2-9-04 is partially dominant, as supported by the degree of dominance in the F2 and F[Formula: see text] populations. Two QTL associated with both RG and EM resistance were detected on chromosomes Vu01 and Vu04. The QTL on Vu01 was most effective against aggressive M. javanica, whereas both QTL were effective against avirulent M. incognita Allelism tests with CB46 x FN-2-9-04 progeny indicated that these parents share the same RKN resistance locus on Vu04, but the strong, broad-based resistance in FN-2-9-04 is conferred by the additive effect of the novel resistance QTL on Vu01. This novel resistance in FN-2-9-04 is an important resource for broadening RKN resistance in elite cowpea cultivars

Individual differences in metabolomics: individualised responses and between-metabolite relationships

Many metabolomics studies aim to find ‘biomarkers’: sets of molecules that are consistently elevated or decreased upon experimental manipulation. Biological effects, however, often manifest themselves along a continuum of individual differences between the biological replicates in the experiment. Such differences are overlooked or even diminished by methods in standard use for metabolomics, although they may contain a wealth of information on the experiment. Properly understanding individual differences is crucial for generating knowledge in fields like personalised medicine, evolution and ecology. We propose to use simultaneous component analysis with individual differences constraints (SCA-IND), a data analysis method from psychology that focuses on these differences. This method constructs axes along the natural biochemical differences between biological replicates, comparable to principal components. The model may shed light on changes in the individual differences between experimental groups, but also on whether these differences correspond to, e.g., responders and non-responders or to distinct chemotypes. Moreover, SCA-IND reveals the individuals that respond most to a manipulation and are best suited for further experimentation. The method is illustrated by the analysis of individual differences in the metabolic response of cabbage plants to herbivory. The model reveals individual differences in the response to shoot herbivory, where two ‘response chemotypes’ may be identified. In the response to root herbivory the model shows that individual plants differ strongly in response dynamics. Thereby SCA-IND provides a hitherto unavailable view on the chemical diversity of the induced plant response, that greatly increases understanding of the system

ASKyphoplan: a program for deformity planning in ankylosing spondylitis

A closing wedge osteotomy of the lumbar spine may be considered to correct posture and spinal balance in progressive thoracolumbar kyphotic deformity caused by ankylosing spondylitis (AS). Adequate deformity planning is essential for reliable prediction of the effect of surgical correction of the spine on the sagittal balance and horizontal gaze of the patient. The effect of a spinal osteotomy on the horizontal gaze is equal to the osteotomy angle. However, the effect of a spinal osteotomy on the sagittal balance depends on both the correction angle and the level of osteotomy simultaneously. The relation between the correction angle, the level of osteotomy and the sagittal balance of the spine can be expressed by a mathematical equation. However, this mathematical equation is not easily used in daily practice. We present the computer program ASKyphoplan that analyses and visualizes the planning procedure for sagittal plane corrective osteotomies of the spine in AS. The relationship between the planned correction angle, level of osteotomy and sagittal balance are coupled into the program. The steps taken during an ASKyphoplan run are outlined, and the clinical application is discussed. The application of the program is illustrated by the analysis of the data from a patient recently treated by a lumbar osteotomy in AS. The software can be used free of charge on the internet at http://www.stega.nl under the heading “research” in the menu

Significant reduction in heart rate variability is a feature of acute decompensation of cirrhosis and predicts 90-day mortality

Background: Heart rate variability (HRV) is reduced in cirrhosis and in conditions of systemic inflammation. Whether HRV is associated with cirrhosis decompensation and development of acute‐on‐chronic liver failure (ACLF) is unknown. // Aims: To (a) validate wireless remote HRV monitoring in cirrhosis decompensation; (b) determine if severely reduced HRV is a surrogate for inflammation and progression of cirrhosis decompensation; (c) assess if measuring HRV determines prognosis in cirrhosis decompensation. // Methods: One hundred and eleven patients at risk of cirrhosis decompensation at two clinical sites were monitored for HRV. Standard deviation of all normal beat‐beat intervals (SDNN) reflecting HRV was assessed using remote monitoring (Isansys Lifetouch) and/or Holter ECG recording. Clinical outcomes and major prognostic scores were recorded during 90‐day follow‐up. // Results: Reduced HRV denoted by lower baseline SDNN, correlated with severity of decompensation (median 14 (IQR 11‐23) vs 33 (25‐42); P < 0.001, decompensated patients vs stable outpatient cirrhosis). Furthermore, SDNN was significantly lower in patients developing ACLF compared to those with only decompensation (median 10 (IQR9‐12) vs 16 (11‐24); P = 0.02), and correlated inversely with MELD and Child‐Pugh scores, and C‐reactive protein (all P < 0.0001) and white cell count (P < 0.001). SDNN predicted disease progression on repeat measures and appeared an independent predictor of 90‐day mortality (12 patients). An SDNN cut‐off of 13.25 ms had a 98% negative predictive value. // Conclusions: This study demonstrates that remote wireless HRV monitoring identifies cirrhosis patients at high risk of developing ACLF and death, and suggests such monitoring might guide the need for early intervention in such patients. Clinical Trial number: NIHR clinical research network CPMS ID 4949

Adherence to physiotherapy clinical guideline acute ankle injury and determinants of adherence: a cohort study

Background. Clinical guidelines are considered important instruments to improve quality in health care. In physiotherapy, insight in adherence to guidelines is limited. Knowledge of adherence is important to identify barriers and to enhance implementation. Purpose of this study is to investigate the ability to adherence to recommendations of the guideline Acute ankle injury, and to identify patient characteristics that determine adherence to the guideline. Methods. Twenty-two physiotherapists collected data of 174 patients in a prospective cohort study, in which the course of treatment was systematically registered. Indicators were used to investigate adherence to recommendations. Patient characteristics were used to identify prognostic factors that may determine adherence to the guideline. Correlation between patient characteristics and adherence to outcome-indicators (treatment sessions, functioning of patient, accomplished goals) was calculated using univariate logistic regression. To calculate explained variance of combined patient characteristics, multivariate analysis was performed. Results. Adherence to individual recommendations varied from 71% to 100%. In 99 patients (57%) the physiotherapists showed adherence to all indicators. Adherence to preset maximum of six treatment sessions for patients with severe ankle injury was 81% (132 patients). The odds to receive more than six sessions were statistically significant for three patient characteristics: females (OR:3.89; 95%CI: 1.41-10.72), recurrent sprain (OR: 6.90; 95%CI: 2.34 - 20.37), co-morbidity (OR: 25.92; 95% CI: 6.79 - 98.93). All factors together explained 40% of the variance. Inclusion of physiotherapist characteristics in the regression model showed that work-experience reduced the odds to receive more than six sessions (OR: 0.2; 95%CI: 0.06 - 0.77), and increased explained variance to 45%. Conclusion. Adherence to the clinical guideline Acute ankle sprain showed that the guideline is applicable in daily practice. Adherence to the guideline, even in a group of physiotherapists familiar with the guideline, showed possibilities for improvement. The necessity to exceed the expected number of treatment sessions may be explained by co-morbidity and recurrent sprains. It is not clear why female patients were treated with more sessions. Experience of the physiotherapist reduced the number of treatment sessions. Quality indicators may be used for audit and feedback as part of the implementation strategy

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Metabolic analysis of the interaction between plants and herbivores

Insect herbivores by necessity have to deal with a large arsenal of plant defence metabolites. The levels of defence compounds may be increased by insect damage. These induced plant responses may also affect the metabolism and performance of successive insect herbivores. As the chemical nature of induced responses is largely unknown, global metabolomic analyses are a valuable tool to gain more insight into the metabolites possibly involved in such interactions. This study analyzed the interaction between feral cabbage (Brassica oleracea) and small cabbage white caterpillars (Pieris rapae) and how previous attacks to the plant affect the caterpillar metabolism. Because plants may be induced by shoot and root herbivory, we compared shoot and root induction by treating the plants on either plant part with jasmonic acid. Extracts of the plants and the caterpillars were chemically analysed using Ultra Performance Liquid Chromatography/Time of Flight Mass Spectrometry (UPLCT/MS). The study revealed that the levels of three structurally related coumaroylquinic acids were elevated in plants treated on the shoot. The levels of these compounds in plants and caterpillars were highly correlated: these compounds were defined as the ‘metabolic interface’. The role of these metabolites could only be discovered using simultaneous analysis of the plant and caterpillar metabolomes. We conclude that a metabolomics approach is useful in discovering unexpected bioactive compounds involved in ecological interactions between plants and their herbivores and higher trophic levels.

What factors affect patients' recall of general practitioners' advice?

<p>Abstract</p> <p>Background</p> <p>In order for patients to adhere to advice, provided by family doctors, they must be able to recall it afterwards. However, several studies have shown that most patients do not fully understand or memorize it. The aim of this study was to determine the influence of demographic characteristics, education, amount of given advice and the time between consultations on recalled advice.</p> <p>Methods</p> <p>A prospective survey, lasting 30 months, was conducted in an urban family practice in Slovenia. Logistic regression analysis was used to identify the risk factors for poorer recall.</p> <p>Results</p> <p>250 patients (87.7% response rate) received at least one and up to four pieces of advice (2.4 ± 0.8). A follow-up consultation took place at 47.4 ± 35.2 days. The determinants of better recall were high school (OR 0.4, 95% CI 0.15-0.99, p = 0.049) and college education (OR 0.3, 95% CI 0.10-1.00, p = 0.050), while worse recall was determined by number of given instructions three or four (OR 26.1, 95% CI 3.15-215.24, p = 0.002; OR 56.8, 95% CI 5.91-546.12, p < 0.001, respectively) and re-test interval: 15-30 days (OR 3.3, 95% CI 1.06-10.13, p = 0.040), 31-60 days (OR 3.2, 95% CI 1.28-8.07, p = 0.013) and more than 60 days (OR 2.5, 95% CI 1.05-6.02, p = 0.038).</p> <p>Conclusions</p> <p>Education was an important determinant factor and warrants further study. Patients should be given no more than one or two instructions in a consultation. When more is needed, the follow-up should be within the next 14 days, and would be of a greater benefit to higher educated patients.</p

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides