Indexed oxygen delivery during pediatric cardiopulmonary bypass is a modifiable risk factor for postoperative acute kidney injury.

BACKGROUND: Acute kidney injury after pediatric cardiac surgery is a common complication with few established modifiable risk factors. We sought to characterize whether indexed oxygen delivery during cardiopulmonary bypass was associated with postoperative acute kidney injury in a large pediatric cohort. METHODS: This was a retrospective analysis of patients under 1 year old undergoing cardiac surgery with cardiopulmonary bypass between January 1, 2013, and January 1, 2020. Receiver operating characteristic curves across values ranging from 260 to 400 mL/min/m2 were used to identify the indexed oxygen delivery most significantly associated with acute kidney injury risk. RESULTS: We included 980 patients with acute kidney injury occurring in 212 (21.2%). After adjusting for covariates associated with acute kidney injury, an indexed oxygen delivery threshold of 340 mL/min/m2 predicted acute kidney injury in STAT 4 and 5 neonates (area under the curve = 0.66, 95% CI = 0.60 - 0.72, sensitivity = 56.1%, specificity = 69.4%). An indexed oxygen delivery threshold of 400 mL/min/m2 predicted acute kidney injury in STAT 1-3 infants (area under the curve = 0.65, 95% CI = 0.58 - 0.72, sensitivity = 52.6%, specificity = 74.6%). CONCLUSION: Indexed oxygen delivery during cardiopulmonary bypass is a modifiable variable independently associated with postoperative acute kidney injury in specific pediatric populations. Strategies aimed at maintaining oxygen delivery greater than 340 mL/min/m2 in complex neonates and greater than 400 mL/min/m2 in infants may reduce the occurrence of postoperative acute kidney injury in the pediatric population.

p-d Orbital Hybridization Induced by a Monodispersed Ga Site on a Pt3 Mn Nanocatalyst Boosts Ethanol Electrooxidation.

Constructing monodispersed metal sites in heterocatalysis is an efficient strategy to boost their catalytic performance. Herein, a new strategy using monodispersed metal sites to tailor Pt-based nanocatalysts is addressed by engineering unconventional p-d orbital hybridization. Thus, monodispersed Ga on Pt3 Mn nanocrystals (Ga-O-Pt3 Mn) with high-indexed facets was constructed for the first time to drive ethanol electrooxidation reaction (EOR). Strikingly, the Ga-O-Pt3 Mn nanocatalyst shows an enhanced EOR performance with achieving 8.41 times of specific activity than that of Pt/C. The electrochemical in situ Fourier transform infrared spectroscopy results and theoretical calculations disclose that the Ga-O-Pt3 Mn nanocatalyst featuring an unconventional p-d orbital hybridization not only promote the C-C bond-breaking and rapid oxidation of -OH of ethanol, but also inhibit the generation of poisonous CO intermediate species. This work discloses a promising strategy to construct a novel nanocatalysts tailored by monodispersed metal site as efficient fuel cell catalysts.

Transcatheter aortic valve replacement with Evolut R versus Sapien 3 in Japanese patients with a small aortic annulus: The OCEAN-TAVI registry.

OBJECTIVES: To compare safety, efficacy, and hemodynamics of transfemoral transcatheter aortic valve replacement (TAVR) using self-expanding and balloon-expandable transcatheter heart valves (THVs) in patients with a small aortic annulus. BACKGROUND: Few studies have directly compared TAVR outcomes using third-generation THVs, focusing on patients with small aortic annuli. METHODS: In a multicenter TAVR registry, we analyzed data from 576 patients with a small annulus and who underwent transfemoral TAVR using third-generation THVs. Propensity score matching was used to adjust baseline clinical characteristics. RESULTS: The device success rate in the overall cohort was 92.0% (Evolut R: 92.1% vs. Sapien 3:92.0%, p = 0.96). One year after TAVR, patients treated with Evolut R maintained a lower mean pressure gradient (mPG) and a higher indexed effective orifice area (iEOA) in the matched cohort {mPG: 9.0 [interquartile range (IQR): 6.0-11.9] vs. 12.0 [IQR: 9.9-16.3] mmHg, p < .001; iEOA: 1.20 [IQR: 1.01-1.46] vs. 1.08 [IQR: 0.90-1.28] cm2 /m2 , p < .001}. However, no significant differences were reported in the incidence of severe prosthesis-patient mismatch and aortic regurgitation at 1 year. Furthermore, both groups showed comparable outcomes with no differences in terms of all-cause mortality (log-lank test, p = .81). CONCLUSIONS: TAVR for patients with a small annulus using third-generation THVs was associated with high device success. Evolut R seems to be superior to Sapien 3 in hemodynamic performance for patients with a small annulus and body surface area up to 1 year after TAVR. Nevertheless, all-cause mortality at 1 year was similar between both groups.

Prediction of LC-MS/MS Properties of Peptides from Sequence by Deep Learning.

Deep learning models for prediction of three key LC-MS/MS properties from peptide sequences were developed. The LC-MS/MS properties or behaviors are indexed retention times (iRT), MS1 or survey scan charge state distributions, and sequence ion intensities of HCD spectra. A common core deep supervised learning architecture, bidirectional long-short term memory (LSTM) recurrent neural networks was used to construct the three prediction models. Two featurization schemes were proposed and demonstrated to allow for efficient encoding of modifications. The iRT and charge state distribution models were trained with on order of 105 data points each. An HCD sequence ion prediction model was trained with 2 × 106 experimental spectra. The iRT prediction model and HCD sequence ion prediction model provide improved accuracies over the start-of-the-art models available in literature. The MS1 charge state distribution prediction model offers excellent performance. The prediction models can be used to enhance peptide identification and quantification in data-dependent acquisition and data-independent acquisition (DIA) experiments as well as to assist MRM (multiple reaction monitoring) and PRM (parallel reaction monitoring) experiment design.

Sex differences in workload-indexed blood pressure response and vascular function among professional athletes and their utility for clinical exercise testing.

PURPOSE: Sex differences in blood pressure (BP) regulation at rest have been attributed to differences in vascular function. Further, arterial stiffness predicts an exaggerated blood pressure response to exercise (BPR) in healthy young adults. However, the relationship of vascular function to the workload-indexed BPR and potential sex differences in athletes are unknown. METHODS: We examined 47 male (21.6 ± 1.7 years) and 25 female (21.1 ± 2 years) athletes in this single-center pilot study. We assessed vascular function at rest, including systolic blood pressure (SBP). Further, we determined the SBP/W slope, the SBP/MET slope, and the SBP/W ratio at peak exercise during cycling ergometry. RESULTS: Male athletes had a lower central diastolic blood pressure (57 ± 9.5 vs. 67 ± 9.5 mmHg, p < 0.001) but a higher central pulse pressure (37 ± 6.5 vs. 29 ± 4.7 mmHg, p < 0.001), maximum SBP (202 ± 20 vs. 177 ± 15 mmHg, p < 0.001), and ΔSBP (78 ± 19 vs. 58 ± 14 mmHg, p < 0.001) than females. Total vascular resistance (1293 ± 318 vs. 1218 ± 341 dyn*s/cm5, p = 0.369), pulse wave velocity (6.2 ± 0.85 vs. 5.9 ± 0.58 m/s, p = 0.079), BP at rest (125 ± 10/76 ± 7 vs. 120 ± 11/73.5 ± 8 mmHg, p > 0.05), and the SBP/MET slope (5.7 ± 1.8 vs. 5.1 ± 1.6 mmHg/MET, p = 0.158) were not different. The SBP/W slope (0.34 ± 0.12 vs. 0.53 ± 0.19 mmHg/W) and the peak SBP/W ratio (0.61 ± 0.12 vs. 0.95 ± 0.17 mmHg/W) were markedly lower in males than in females (p < 0.001). CONCLUSION: Male athletes displayed a lower SBP/W slope and peak SBP/W ratio than females, whereas the SBP/MET slope was not different between the sexes. Vascular functional parameters were not able to predict the workload-indexed BPR in males and females.

Impact of valve size, predicted effective and indexed effective orifice area after aortic valve replacement.

INTRODUCTION: The impact of manufacturer labeled prosthesis size and predicted effective orifice area (EOA) on long-term survival after aortic valve replacement is not clear although indexed effective orifice area (iEOA) has been associated with worse survival. METHODS: Data was retrospectively collected from Jan 2000-Dec 2019 for prosthesis type, model, and size for isolated aortic valve replacements. Stratified survival was compared between groups and subgroups for labeled valve size, EOA and predicted patient prosthesis mismatch (PPM). RESULTS: A total of 3444 patients were included. Moderate and severe PPM was 15.6% and 1.6%, respectively. Cumulative lifetime hazard was worse for biological valves (mortality: biological 77.7% vs. mechanical 64.8%, p = .001). Moderate prosthetic aortic stenosis (AS), (EOA = 1-1.5 cm2 ) was 12.1% and severe prosthetic AS (EOA ≤ 1 cm2 ) was 0.8%, respectively. Survival was 10.5 ± 0.4 years with moderate to severe prosthetic AS (EOA≤1.5 cm2 ) versus 12.6 ± 0.2 years with mild to no prosthetic AS (EOA>1.5 cm2 ), p = .001. Worse survival in the presence of moderate-severe prosthetic AS was seen with biological valves (9.7 ± 0.4 years vs. 11.2 ± 0.2 years, p = .001 for EOA≤1.5, >1.5 cm2 , respectively). Moderate to severe PPM was associated with worse survival (11.1 ± 0.4 years for iEOA ≤ 0.85 cm2 /m2 vs. 12.5 ± 0.2 years with iEOA > 0.85 cm2 /m2 , p = .001). Moderate to severe PPM predicted worse long term survival (hazard ratio: 3.56; 95% confidence interval: 1.37-9.25; p = .009). CONCLUSION: Predicted prosthetic moderate to severe AS and moderate to severe PPM adversely affect long term survival. Smaller valves are associated with reduced survival.

Correct use of non-indexed eGFR for drug dosing and renal drug-related problems at hospital admission.

PURPOSE: Two to seven percent of the German adult population has a renal impairment (RI) with an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. This often remains unrecognized and adjustment of drug therapy is lacking. To determine renal function in clinical routine, the CKD-EPI equation is used to calculate an indexed eGFR (ml/min/1.73m2). For drug dosing, it has to be individualized to a non-indexed eGFR (ml/min) by the patient's body surface area. Here, we investigated the number of patients admitted to urological wards of a teaching hospital with RI between July and December 2016. Additionally, we correctly used the eGFRnon-indexed for drug and dosage adjustments and to analyse the use of renal risk drugs (RRD) and renal drug-related problems (rDRP). METHODS: In a retrospective observational study, urological patients with pharmacist-led medication reconciliation at hospital admission and eGFRindexed (CKD-EPI) of 15-59 ml/min/1.73m2 were identified. Indexed eGFR (ml/min/1.73m2) was recalculated with body surface area to non-indexed eGFR (ml/min) for correct drug dosing. Medication at admission was reviewed for RRD and based on the eGFRnon-indexed for rDRP, e.g. inappropriate dose or contraindication. RESULTS: Of 1320 screened patients, 270 (20.5%) presented with an eGFRindexed of 15-59 ml/min/1.73m2. After readjustment, 203 (15.4%) patients had an eGFRnon-indexed of 15-59 ml/min. Of these, 190 (93.6%) used ≥ 1 drugs at admission with 660 of 1209 (54.7%) drugs classified as RRD. At least one rDRP was identified in 115 (60.5%) patients concerning 264 (21.8%) drugs. CONCLUSION: Renal impairment is a common risk factor for medication safety in urologic patients admitted to a hospital. Considerable shifts were seen in eGFR-categories when correctly calculating eGFRnon-indexed for drug dosing purposes. The fact that more than half of the study patients showed rDRP at hospital admission underlines the need to consider this risk factor appropriately.

Determinants of LA reservoir strain: Independent effects of LA volume and LV global longitudinal strain.

BACKGROUND: Left atrial (LA) deformation during the reservoir phase (LASr) has demonstrated strong prognostic value in different clinical settings. Although determinants of left atrial reservoir strain including left atrial relaxation, left atrial compliance, and left ventricular longitudinal systolic function are fairly well defined, there is incomplete information regarding the effect of left atrial volume on this relationship which is the focus of our study. METHOD: Consecutive patients without prior cardiac disease referred for transthoracic echocardiography were prospectively recruited. All participants underwent clinical assessment, transthoracic echocardiography (TTE), and screening exercise stress test. Only patients with normal left ventricular ejection fraction (LVEF) without left ventricular hypertrophy (LVH) or myocardial ischemia on stress testing were included. RESULTS: A total of 260 patients (57% male, mean age 59 ± 14 years) were included. 70% had hypertension, 33% had diabetes mellitus, and 31% had both HTN and DM. On multivariate analysis, age, e', LAVI, and LV GLS (P < .01 for all) showed an independent association with LASr. Of interest, at lower tertiles of LAVI, a linear decrease in LASr was observed parallel to worsening LV GLS, whilst at higher tertiles of LAVI, the reduction in LASr was non-linear implying that LA enlargement, consequent to LA remodeling, had an incremental effect on LASr. CONCLUSION: Age, e', LV GLS, and LAVI were independently associated with LASr. LA remodeling reflected by larger LAVI had an incremental negative association with LASr independent of LV GLS.

JOA: Joint Overlap Analysis of multiple genomic interval sets.

BACKGROUND: Next-generation sequencing (NGS) technologies have produced large volumes of genomic data. One common operation on heterogeneous genomic data is genomic interval intersection. Most of the existing tools impose restrictions such as not allowing nested intervals or requiring intervals to be sorted when finding overlaps in two or more interval sets. RESULTS: We proposed segment tree (ST) and indexed segment tree forest (ISTF) based solutions for intersection of multiple genomic interval sets in parallel. We developed these methods as a tool, Joint Overlap Analysis (JOA), which takes n interval sets and finds overlapping intervals with no constraints on the given intervals. The proposed indexed segment tree forest is a novel composite data structure, which leverages on indexing and natural binning of a segment tree. We also presented construction and search algorithms for this novel data structure. We compared JOA ST and JOA ISTF with each other, and with other interval intersection tools for verification of its correctness and for showing that it attains comparable execution times. CONCLUSIONS: We implemented JOA in Java using the fork/join framework which speeds up parallel processing by taking advantage of all available processor cores. We compared JOA ST with JOA ISTF and showed that segment tree and indexed segment tree forest methods are comparable with each other in terms of execution time and memory usage. We also carried out execution time comparison analysis for JOA and other tools and demonstrated that JOA has comparable execution time and is able to further reduce its running time by using more processors per node. JOA can be run using its GUI or as a command line tool. JOA is available with source code at https://github.com/burcakotlu/JOA/ . A user manual is provided at https://joa.readthedocs.org.

Improved Estimation of Total Blood Volume Can Provide a Reliable Prediction of Dilutional Hematocrit and Oxygen Delivery during Cardiopulmonary Bypass.

Optimal oxygen delivery during cardiopulmonary bypass (CPB) for open heart surgery is crucial to protect organ function, improve outcomes, and reduce hospital stay. Effective preparation for optimal oxygen delivery during CPB is dependent on a reliable estimation of total blood volume (TBV) to accurately predict dilutional hematocrit (Hct) and calculate indexed oxygen delivery (iDO2). Unreliable estimation of TBV is a major reason for inaccurate prediction of dilutional Hct and iDO2. We performed a retrospective study of 113 patients who underwent cardiac surgery to compare the accuracy of predicted versus measured Hct and iDO2. We used four conventional methods of TBV estimation: 1) weight based A; 70 mL/kg for all patients, 2) weight based B; 70 mL/kg for males and 65 mL/kg for females, 3) Allen's formula, and 4) Nadler's formula. We found that TBV estimated by Allen's formula predicted dilutional Hct better than the other three. However, all four methods overestimate TBV when Hct is low and underestimate when Hct is high, suggesting that TBV is dependent on Hct in addition to body size and gender. Our analysis indicates that two individuals with the same body size and gender can have different TBV depending on Hct. We revised Allen's formula by adding a component that adjusts TBV depending on Hct to provide a more accurate prediction of dilutional Hct and iDO2.

Primality, Fractality, and Image Analysis.

This paper deals with the hidden structure of prime numbers. Previous numerical studies have already indicated a fractal-like behavior of prime-indexed primes. The construction of binary images enables us to generalize this result. In fact, two-integer sequences can easily be converted into a two-color image. In particular, the resulting method shows that both the coprimality condition and Ramanujan primes resemble the Minkowski island and Cantor set, respectively. Furthermore, the comparison between prime-indexed primes and Ramanujan primes is introduced and discussed. Thus the Cantor set covers a relevant role in the fractal-like description of prime numbers. The results confirm the feasibility of the method based on binary images. The link between fractal sets and chaotic dynamical systems may allow the characterization of the Hénon map only in terms of prime numbers.

Progress and prospects of medical education research in Asian Countries.

BACKGROUND AND OBJECTIVES: Medical education has a profound impact on health care system. Progress in achieving medical education research goals varies over time and across countries. This study aimed to investigate the medical education research ambience in Asia during the period 1965-2015. METHODS: We investigated the bibliometric indicators of 49 Asian states in medical education research from 1965-2015. The data about Asian countries, their per capita GDP, expenditure on R&D, universities and indexed scientific journals were collected. We recorded medical education related research documents published in Institute of Scientific Information (ISI) Web of Science, Thomson Reuters during the period 1965-2015. RESULTS: Asian countries collectively published 12721799 research articles, among them 40628 (0.31%) publications were in medical education. China contributed total of 3351565 articles among which 5414 (0.16%) research articles were in medical education; India added 1328725 papers with 4563 (0.34%) in medical education; Japan produced 3080257 papers with 4199 (0.13%) in medical education; Israel 561531 with 3848 (0.68%) in medical education; and lastly, Georgia contributed a total of 296532 research articles with 2565 (0.86%) in medical education. CONCLUSIONS: In Asia, the top five countries in medical education research are China, Georgia, Israel, Japan and India. The countries at low ranking are Yemen, Palestine, Myanmar, Kazakhstan, Syria and Armenia. In Asian states, the overall performance in medical science research needs policies to enhance its impact globally. Medical universities should offer research programs for learning and understanding the challengeable issues in medical education research.

Early and Mid-term Outcome of the St. Jude Medical Regent 19-mm Aortic Valve Mechanical Prosthesis. Functional and Haemodynamic Evaluation.

BACKGROUND AND OBJECTIVES: The aim of the present study is to report the early and mid-term clinical and haemodynamic results of the St Jude Medical Regent 19-mm aortic mechanical prothesis (SJMR-19). MATERIALS AND METHODS: Between January 2002 and January 2012, 265 patients with aortic valve disease underwent AVR (Aortic Valve Replacement) with a SJMR-19 (St Jude Medical Regent Nr.19). There were 51 males. Mean age was 67.5±12.72years and mean body surface area (BSA) was 1.67±0.14m2. Thirty-six patients required annulus enlargement. The mean follow-up was 34.5±18.8months (range 6-60 months). All patients underwent echocardiographic examination at discharge and within 1 year after surgery. RESULTS: There were 14 (5.3%) hospital deaths. Six of the hospital deaths were identified in patients undergoing reoperation, significantly higher than patients undergoing first time operation (p=0.0001). Also the postoperative mortality was significantly higher in patients undergoing annulus enlargement versus patients not requiring annulus enlargement (p=0.02). The mean transprosthesis gradient at discharge was 19±9mmHg. At 6 months follow-up the mean NYHA FC class was 1.6±0.5 significantly lower than preoperatively 2.4±0.75 (p <0.0001). The M-TPG was 15.2±6.5mmHg within 1 year after surgery. Left ventricular mass (LVM) and indexed left ventricular mass (LVMi) were significantly lower than preoperatively The actuarial survival and cumulative freedom from reoperation at 1, 2 and 3 years follow-up were 99.5%, 97.5%, 96.7% and 99.2%, 96.5%, 94.5% respectively. The cumulative actuarial free-events survival at 4 years was 92%. The Cox model identified age (p=0.015), LVEF≤35% (p=0.043), reoperation (p=0.031), combined surgery (p=0.00002), and annulus enlargement (p=0.015) as strong predictors for poor actuarial free-major events survival. CONCLUSIONS: The SJMR-19 offers excellent postoperative clinical, haemodynamic outcome and LVMi reduction in patients with small aortic annulus. These data demonstrate that the modern St Jude small mechanical protheses do not influence the intermediate free-reoperation survival.

Advanced Precursor Ion Selection Algorithms for Increased Depth of Bottom-Up Proteomic Profiling.

Conventional TopN data-dependent acquisition (DDA) LC-MS/MS analysis identifies only a limited fraction of all detectable precursors because the ion-sampling rate of contemporary mass spectrometers is insufficient to target each precursor in a complex sample. TopN DDA preferentially targets high-abundance precursors with limited sampling of low-abundance precursors and repeated analyses only marginally improve sample coverage due to redundant precursor sampling. In this work, advanced precursor ion selection algorithms were developed and applied in the bottom-up analysis of HeLa cell lysate to overcome the above deficiencies. Precursors fragmented in previous runs were efficiently excluded using an automatically aligned exclusion list, which reduced overlap of identified peptides to ∼10% between replicates. Exclusion of previously fragmented high-abundance peptides allowed deeper probing of the HeLa proteome over replicate LC-MS runs, resulting in the identification of 29% more peptides beyond the saturation level achievable using conventional TopN DDA. The gain in peptide identifications using the developed approach translated to the identification of several hundred low-abundance protein groups, which were not detected by conventional TopN DDA. Exclusion of only identified peptides compared with the exclusion of all previously fragmented precursors resulted in an increase of 1000 (∼10%) additional peptide identifications over four runs, suggesting the potential for further improvement in the depth of proteomic profiling using advanced precursor ion selection algorithms.

Virtual Distances Methodology as Verification Technique for AACMMs with a Capacitive Sensor Based Indexed Metrology Platform.

This paper presents a new verification procedure for articulated arm coordinate measuring machines (AACMMs) together with a capacitive sensor-based indexed metrology platform (IMP) based on the generation of virtual reference distances. The novelty of this procedure lays on the possibility of creating virtual points, virtual gauges and virtual distances through the indexed metrology platform's mathematical model taking as a reference the measurements of a ball bar gauge located in a fixed position of the instrument's working volume. The measurements are carried out with the AACMM assembled on the IMP from the six rotating positions of the platform. In this way, an unlimited number and types of reference distances could be created without the need of using a physical gauge, therefore optimizing the testing time, the number of gauge positions and the space needed in the calibration and verification procedures. Four evaluation methods are presented to assess the volumetric performance of the AACMM. The results obtained proved the suitability of the virtual distances methodology as an alternative procedure for verification of AACMMs using the indexed metrology platform.

Research productivity of Gulf Cooperation Council (GCC) countries in science and social sciences.

OBJECTIVE: To investigate the research progress of Gulf Cooperation Council countries in science and social sciences. METHODS: This study was conducted in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, from June 2014 to February 2015.All research documents related to the 1996-2013 period having an affiliation with Gulf Cooperation Council countries, including Saudi Arabia, the United Arab Emirates, Kuwait, Qatar, Bahrain and Oman, were tracked. The main source for data-gathering was World Association of Universities, Sci-mago Journal and Country ranking and Web of Science Institute of Scientific Information (ISI) Thomson Reuters. RESULTS: Of the 544 institutions produced research papers, 141(25.92%) were universities or degree-awarding institutes, 372(68.38%) were research institutes and 31(5.7%) were Institute of Scientific Information-indexed scientific journals. The number of degree awarding institutes were 68(48.23%) in Saudi Arabia, 33(23.4%) in the United Arab Emirates and 12(8.51%) in Qatar. The total number of publications contributed by the region was 133638 (Mean ± SD: 22273 ± 26302.20); citable documents 127739 (Mean ± SD: 21289.83 ±25241.22); self-citations 105,716 (Mean ± SD: 17619.33 ± 23328.44); total citations 756141 (Mean ± SD: 126023.5 ± 143260.95) and citations per documents 33.22 (Mean ± SD: 5.53 ± 1.09).The overall and mean Hirschindex was 513and 85.5± 35.39. CONCLUSIONS: Among Gulf Cooperation Council countries, Saudi Arabia was the most productive country producing adequate number of research publications, citations and holding the highest Hirsch index value.

Leaf phenomics: a systematic reverse genetic screen for Arabidopsis leaf mutants.

The study and eventual manipulation of leaf development in plants requires a thorough understanding of the genetic basis of leaf organogenesis. Forward genetic screens have identified hundreds of Arabidopsis mutants with altered leaf development, but the genome has not yet been saturated. To identify genes required for leaf development we are screening the Arabidopsis Salk Unimutant collection. We have identified 608 lines that exhibit a leaf phenotype with full penetrance and almost constant expressivity and 98 additional lines with segregating mutant phenotypes. To allow indexing and integration with other mutants, the mutant phenotypes were described using a custom leaf phenotype ontology. We found that the indexed mutation is present in the annotated locus for 78% of the 553 mutants genotyped, and that in half of these the annotated T-DNA is responsible for the phenotype. To quickly map non-annotated T-DNA insertions, we developed a reliable, cost-effective and easy method based on whole-genome sequencing. To enable comprehensive access to our data, we implemented a public web application named PhenoLeaf (http://genetics.umh.es/phenoleaf) that allows researchers to query the results of our screen, including text and visual phenotype information. We demonstrated how this new resource can facilitate gene function discovery by identifying and characterizing At1g77600, which we found to be required for proximal-distal cell cycle-driven leaf growth, and At3g62870, which encodes a ribosomal protein needed for cell proliferation and chloroplast function. This collection provides a valuable tool for the study of leaf development, characterization of biomass feedstocks and examination of other traits in this fundamental photosynthetic organ.

VALIDATION OF AN INDEXED RADIOTHERAPY HEAD POSITIONING DEVICE FOR USE IN DOGS AND CATS.

Setup variability affects the appropriate delivery of radiation and informs the setup margin required to treat radiation patients. Twenty-four veterinary patients with head and neck cancers were enrolled in this prospective, cross-sectional study to determine the accuracy of an indexed board immobilization device for positioning. Couch position values were defined at the first treatment based on setup films. At subsequent treatments, patients were moved to the previously defined couch location, orthogonal films were acquired, table position was modified, and displacement was recorded. The mean systematic displacement, random displacement, overall displacement, and mean displacement values of the three-dimensional (3D) vector were calculated. Three hundred thirty-two pairs of orthogonal setup films were analyzed for displacement in cranial-caudal, lateral, and dorsal-ventral directions. The mean systematic displacements were 0.5, 0.8, and 0.5 mm, respectively. The mean random displacements were 1.0, 1.1, and 0.7 mm, respectively. The overall displacements were 1.1, 1.4, and 0.9 mm, respectively. The mean 3D vector value was 1.6 mm with a standard deviation of 1.2 mm. Ninety-five percent of the vectors were <3.6 mm. These values were compared to data obtained with a previously used immobilization device. A t-test was used to compare the two devices. The 3D vector, random displacement in all directions, and overall displacement in the cranial-caudal and dorsal-ventral directions were significantly smaller than displacements with the previous device. The precision and accuracy of the indexed board device was superior to the historical head and neck device.

Premarital genetic screening for beta thalassemia carrier status of indexed families using HbA2 electrophoresis.

OBJECTIVE: To devise a strategy for prevention of beta thalassemia in newborns through reliable screening of indexed families. METHODS: The cross-sectional study was conducted over six months in 2011 and comprised blood samples collected from subjects belonging to different ethnic groups from families of beta thalassemia major children registered with the Abbottonian Medical Association Blood Care Centre, Abbottabad, in Pakistan's Khyber Pakhtunkhwa province. Electrophoretic separation of human haemoglobin like A, F, S and C was done and then haemoglobin in the gel was immobilised in a fixative solution and the gel was dried to a film. Haemoglobin pattern was visualised by staining the film with a protein-specific stain. The pattern was quantified by densitometry. RESULTS: Of the 98 samples, 57(58.2%) had b-thalassemia trait with elevated haemoglobin alpha 2 level, and 41(41.8%) had normal level. Out of the 57 carriers, 33(57.89%) were males and 24(42.10%) were females. Mean age of carriers was 11.65±6.25 years compared to 10.93±7.75 in normal patients. Mean haemoglobin alpha 2 level of carriers was 5.2±0.56% compared to 2.34±0.57% in normal subjects. CONCLUSIONS: Carrying out mass screening programmes throughout Pakistan for the detection of thalassemia carriers and providing them the benefit of marriage counselling may decrease the incidence of thalassemia Major.

Indexing glomerular filtration rate to body surface area: clinical consequences.

BACKGROUND: Kidney function is mostly expressed in terms of glomerular filtration rate (GFR). A common feature is the expression as ml/min per 1.73 m(2) , which represents the adjustment of the individual kidney function to a standard body surface area (BSA) to allow comparison between individuals. We investigated the impact of indexing GFR to BSA in cancer patients, as this BSA indexation might affect the reported individual kidney function. METHODS: Cross-sectional study of 895 adults who had their kidney function measured with (51) chrome ethylene diamine tetraacetic acid. Mean values of BSA-indexed GFR vs. mean absolute GFR were analyzed with a t-test for paired data. Bland-Altman plot was used to analyze agreement between the indexed and absolute GFR values. RESULTS AND CONCLUSION: BSA-GFR in patients with a BSA <1.60 m(2) overestimated GFR with a bias of 10.08 ml/min (11.46%) and underestimated GFR in those with a BSA >2 m(2) with a bias up to -20.76 ml/min (-23.59%). BSA is not a good normalization index (NI) in patients with extreme body sizes. Therefore, until a better NI is found, we recommend clinicians to use the absolute GFR to calculate individual drug chemotherapy dosage as well as express individual kidney function.