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Influence of admission functional status on functional gain and efficiency of rehabilitation in first time stroke patients.

The purpose of this study was to determine whether the admission functional status influences the functional gain and efficiency of stroke rehabilitation. We prospectively studied 105 first time stroke patients consecutively admitted to the inpatient rehabilitation department of a university hospital during 1997. Functional status was assessed with the Functional Independence Measure (FIM) instrument on admission and discharge of inpatient rehabilitation program. The patients were stratified into three groups according to their FIM total scores on admission, i.e., 18 to 36, 37 to 72, and 73 to 126. One-way ANOVA with Tukey's studentized range tests indicated that patients with FIM total scores of > or = 73 at admission were significantly younger (58.2 +/- 12.3 yr) and scored lower functional gain (16.6 +/- 11.7) than those who scored of < or = 36 (66.3 +/- 9.4 yr) of age and functional gain of (27.6 +/- 23.3). However, there were no significant differences on rehabilitation efficiency among the three groups. The findings of this study suggest that the functional groups stratified by admission FIM score seem to predict the degree of functional gain for first time stroke patients after inpatient rehabilitation.

Adult↗

Investigating temporal pole function by functional imaging.

Although the role of the temporal lobe especially its mesial part is becoming clearer, that of the temporal pole remains more mysterious. Temporal pole function can be investigated in various ways: by comparing anatomical and clinical data; through experiments in animals; and by using functional imaging techniques. Anatomo-clinical studies have suggested that the temporal pole is important in autobiographical memory; and studies in monkeys (conditioning and lesional experiments) have revealed a role for the temporal pole in a variety of functions, including taste and olfaction, face recognition, visual discrimination of two-dimensional pictures, and the mnemonic functions of matching and learning. Functional imaging techniques, whether based on positron emission tomography (PET) or magnetic resonance imaging (MRI), make it possible to observe the functioning of the temporal pole in vivo in both healthy control subjects and patients. Initially, this type of approach was simply used to confirm observations made in animals. More recently it has shed light on other functions, especially with respect to processes associated with linguistic integration, which underlie the ability to make lexical and semantic links between different words and make it possible to understand a story in a general way without prior specific knowledge. Studies of epileptic, demented and schizophrenic patients have revealed that abnormal patterns of temporal pole function are typical in all these conditions.

Animals↗

Evaluation of functional capacity after stroke with special emphasis on motor function and activities of daily living.

In a multidisciplinary study comprising 280 patients with acute cerebrovascular disease (median age 76, range 30-96 years), instruments for functional assessment in stroke care were developed. The improvements of motor function and activities of daily living were investigated during a period of up to one year after a stroke. A new chart for motor capacity assessment, which includes both the paretic and the non-paretic side, modified after that of Fugl-Meyer et al, was tested for its reliability and validity. At the same time the Activity Index of Hamrin & Wohlin was further tested. The internal consistency reliability measured with the standardized item alpha method confirmed that the two instruments have high homogeneity. Construct validity was investigated by factor analysis and showed a logical structure. The predictive validity of the scores on admission was significant and the two tools had a satisfactory predictive capacity for survival and later functional outcome. The improvements in different motor functions were followed up for up to one year after the stroke among the 183 one-year survivors. In patients with minor impairment, the improvement occurred mostly during the first week. Patients with moderate or moderately severe impairment improved more continuously for up to three months, while the few surviving patients with very severe impairment continued to recover to some extent even after three months. Older patients with severe functional loss seemed to improve more slowly and not as well as younger patients with equivalent impairment. The patterns of instrumental activities of daily living (I-ADL), such as household work, locomotion, psychosocial functions and intellectual activities, were investigated in the 207 three-month survivors and the 183 one-year survivors. At both the three-month and the one-year follow-ups the scores had decreased considerably, compared with before the stroke, for all activities except locomotion, and many patients were dependent on somebody else for help. The same group of patients was also examined by a Standardized Practical Equipment (SPE) test constructed by Tömquist three months and one year after the stroke. The construct validity of the SPE test was estimated through factor analysis. Three factors emerged, one concerning mainly cognitive factors and co-ordination, one concerning hand function and one concerning mainly mobility and balance. The instruments developed in the course of this study have proved to be reliable and valid, and useful in assessing functional losses and following progress. The tools are well suited for any clinical settings and for home care examinations as well as research.

Activities of Daily Living↗

[Left ventricular function during atrial fibrillation assessed by left ventricular function curve using ECG-gated blood pool scintigraphy].

Cardiac function is difficult to assess in patients with atrial fibrillation due to the widely fluctuating cycle lengths resulting in variable ventricular hemodynamics. With respect to ECG-gated blood pool scintigraphy, distortion of the time activity curve occurs due to a summation of irregular cycle lengths. Therefore, performing such a study has been regarded meaningless. To evaluate left ventricular function during atrial fibrillation using scintigraphic technique, a new processing algorithm was devised to make multiple gated images which are discriminated by the preceding R-R interval, and left ventricular filling and function curves were established. The left ventricular filling curve, obtained by plotting end-diastolic volume against the preceding R-R intervals demonstrated an impairment of blood filling in cases of mitral stenosis and constrictive pericarditis, which resolved after mitral commissurotomy in case of mitral stenosis. The left ventricular function curve, established by plotting stroke volume against end-diastolic volume, was analyzed according to indices such as "slope" and "position". Both of these indices were significantly reduced in relation to the severity of heart failure according to the NYHA's functional classification and cardiomegaly on chest radiography. On individual comparisons of underlying diseases, the indices decreased in the following order; lone atrial fibrillation, hyperthyroidism, aging, hypertension, mitral valve disease, ischemic heart disease, dilated cardiomyopathy and aortic regurgitation. The indices correlated closely with ejection fraction. In cases of mitral regurgitation, however, the function curves were situated to the right and above those of lone atrial fibrillation and decreased in slope despite the fairly well-maintained ejection fraction. After treatment with digitalis and/or diuretics, the function curves shifted to the left and upward. In conclusion, left ventricular filling and function curves based on a newly-devised algorithm of ECG-gated blood pool scintigraphy are of considerable clinical value in evaluating cardiac performance in patients with atrial fibrillation. They are widely applicable to the assessment of therapeutic and interventional effects.

Atrial Fibrillation↗

[Studies on renal function following cardiac operations--with special reference to postoperative cardiac function].

Effect of cardiac function on postoperative renal function was studied in 54 cases. These cases were divided into two groups according to postoperative cardiac function. Group A was good cardiac function group (27 cases; the value of C.I. was below 2.2L/min/m2 less than once through all examinations after operation). Group B was low cardiac function group (27 cases; the value of C.I. was below 2.2L/min/m2 more than twice through all examinations after operation). Significant differences were found in cardiac index, mean arterial pressure, left, arterial pressure and total vascular resistance in two groups. Significant differences were not found in urinary volume and FENa in two groups. In creatinine clearance and free water clearance significant differences were found from early postoperative period, and group A showed better renal function than group B. Serum Na, serum K and urinary Na:K ratio were not significantly different between two groups. Difference of plasma renin activity was not significant, but plasma aldosterone was significantly higher in group B than in group A during postoperative period. In group B, four patients developed nonoliguric acute renal failure, eventually resulting in MOF. The author concluded that postoperative cardiac function played the most important role on the state of postoperative renal function.

Acute Kidney Injury↗

[Several homeostatic renal functions in hypertensive and nephrotic syndromes of chronic functionally compensated glomerulonephritis].

Homeostatic renal functions in nephrotic syndrome (NS) and arterial hypertension were studied the data on 240 patients with functionally compensated chronic glomerulonephritis (CGN). Benign arterial hypertension did not make a considerable effect on renal functions. In NS there was a selective decrease in the functions, particularly affected in the tubulointerstitial component (TIC) of CGN (concentration and ammonium secretory functions). These functions were affected to the maximum in proteinuria over 9.0 g/day. The NS adverse effect on renal transport processes was not dependent on the TIC presence. In CGN accompanied by moderate proteinuria, even a moderate decrease in renal concentration function or a considerable decrease in ammonium secretory function suggested the TIC presence. Against a background of the NS the presence of CGN TIC could be supposed only in the detection of maximum urine osmolarity not exceeding 600 mmol/l.

Adolescent↗

Functional comparative histology. 1. Communication: comparative and functional aspects of histology.

Comparative histology demonstrates the different ways through which a function can be performed by one or more structures. The functional approach offers the widest comparison, much wider than any morphologic comparison would be able to do. The function adds the physiological and biochemical approach to the picture. Histochemistry bridges the gap between both, the comparative and functional aspect, as well as tissue and organ culture. The tissues show a variation in their phylogenetic age of appearance and taxonomic distribution. Comparative functional histology is a basic science of the various biological disciplines. Comparative functional histology is also a basic pillar of experimental pathology. The functional frame of comparative histology has been outlined. The following communications of the series listed below will give a detailed description of special aspects of comparative functional histology.

Animal Population Groups↗

Heart function in patients with chronic glomerulonephritis and mildly to moderately impaired renal function. An echocardiographic study.

UNLABELLED: Left ventricular hypertrophy and diastolic heart dysfunction have been reported in essential hypertension and in patients with chronic renal failure, treated with haemodialysis, but a close association with blood pressure (BP) level has not been uniformly documented. Thus, other factors could be involved in the pathogenesis of cardiac dysfunction. The aims of the present echocardiographic study were to investigate cardiac morphology and function in patients with chronic glomerulonephritis with mildly to moderately impaired renal function, and to study the relation between echocardiographic findings and glomerular filtration rate (GFR), BP and age. Twenty patients with chronic glomerulonephritis and 14 healthy controls, of the same age- and sex-distribution, were examined by 2D-, M-mode and pulsed-wave Doppler echocardiography. In patients, GFR was determined as plasma clearance of Cr-EDTA. The patients had significantly thicker left ventricular (LV) posterior walls in end diastole (8.7 vs 8.1 mm, p < 0.05), and a higher LV mass index (106.5 vs 93.8 g/m2, p < 0.05). Systolic functional indices, i.e. LV fractional shortening and LV ejection fraction, were statistically significantly lower in patients than in controls (p < 0.05). LV diastolic function in patients was characterized by a statistically significantly lower early peak flow velocity (E-Vmax) (0.66 compared with 0.8 m/s) and early to late peak flow velocity ratio (E/A ratio) (1.07 vs 1.41), as well as E/A ratio of time velocity indices (VTI-E/A) (1.45 vs 1.99) (p < 0.05). The right ventricular filling indices showed a tendency towards a lower E-Vmax in patients (0.55 compared with 0.62 m/s, p = 0.1). In patients, statistically significant negative correlations were found between age and mitral E/A ratio (r = -0.76, p < 0.0001), as well as LV VTI-E/A(r = -0.81, p < 0.0001). The same trend was seen for the tricuspid E/A ratio. No statistically significant correlations were found in patients between mitral or tricuspid E/A ratio and GFR, BP, LV mass or heart rate. IN CONCLUSION: in a group of patients with chronic glomerulonephritis and mildly to moderately impaired renal function, it was found by means of echocardiography that there was a higher LV mass index and decreased systolic function, when compared with healthy controls. In addition, the patients had diastolic dysfunction of primarily the left ventricle. The echocardiographic findings were not correlated to BP level or renal function. This suggests that factors other than GFR or BP per se might be involved in the pathogenesis of cardiac dysfunction, at an early stage.

Adult↗

Antero-posterior functional coupling at sleep onset: changes as a function of increased sleep pressure.

The use of the directed transfer function (DTF), an advanced computational analysis of electroencephalogaphic (EEG) data, which provides an estimation of the direction of the information flow underlying cortico-cortical functional coupling, has shown that the presleep period is characterized by posterior-to-anterior functional cortical coupling, while at sleep onset there is an inversion of that direction. This finding supported the idea that anterior cortical areas first synchronize sleep EEG activity. The aim of the present study was to assess the changes of functional coupling between anterior and posterior midline cortical areas during the sleep onset process when sleep pressure is heightened by a selective slow-wave sleep (SWS) deprivation. The hypothesis was that the anterior-to-posterior direction of the cortical functional coupling at sleep onset is enhanced by SWS deprivation. Ten normal right-handed male students slept for six consecutive nights in the laboratory (1: adaptation, 2: baseline, 3: baseline with awakenings, 4 and 5: SWS deprivations, 6: recovery), with standard polysomnographic recordings. The DTF was computed on data recorded during nights two and six from anterior (Fz(A1)) and posterior (Pz(A1), Oz(A1)) derivations. Results showed that, during the recovery night, the anterior-to-posterior direction of functional cortical coupling is already present in the presleep period, indicating that SWS deprivation advances the shift to an anterior-to-posterior directionality of functional cortical coupling, possibly as a consequence of heightened sleep pressure. These findings support the notion that a spread of synchronizing signals from associative prefrontal to posterior areas play a role in the wake-sleep transition.

Adult↗

Influence of functional tricuspid regurgitation on right ventricular function.

BACKGROUND: Although right ventricular (RV) function has been extensively studied during the past decade, few reports have described the influence of functional tricuspid regurgitation (TR) on RV function. METHODS: One hundred forty-two patients with left-side valvular heart disease associated with TR were enrolled in the study and divided into three groups according to tricuspid annular diameter: group 1 (n = 66), tricuspid annular diameter less than 40 mm; group 2 (n = 58), tricuspid annular diameter of 40 to 50 mm; and group 3 (n = 18), tricuspid annular diameter greater than or equal to 50 mm. In groups 2 and 3, the right heart parameters had deteriorated to the point that TR repair was necessary. The mean follow-up period was 102 months after the operation. RESULTS: In each of the three groups, as pulmonary arteriolar resistance index increased, RV forward stroke work index increased in a linear fashion. The slope of the linear regression line was progressively less in group 1, 2, and 3 preoperatively. Postoperatively, this line moved in a parallel manner in group 1 and became steeper in group 2, consequently becoming similar in both groups. However, in group 3, although the slope became steeper in spite of a remarkable decrease of TR, it remained less when compared with groups 1 and 2. In addition, the right heart parameters also improved, but still remained worse in group 3 than group 2; 7 patients undergoing a flexible annuloplasty have shown gradual aggravations in TR and late postoperative clinical manifestations. CONCLUSIONS: Functional TR with severely dilated annulus may produce an irreversible deterioration of RV function. The preoperative relationship between pulmonary arteriolar resistance index and RV forward stroke work index, that is, RV systolic function to pressure afterload, might predict a postoperative fate of the right heart function.

Cardiac Catheterization↗

Biventricular pacing in end-stage heart failure improves functional capacity and left ventricular function.

BACKGROUND: Asynchronous patterns of contraction and relaxation may contribute to hemodynamic and functional impairment in heart failure. In 1993, we introduced biventricular pacing as a novel method to treat heart failure by synchronous stimulation of the right and left ventricles after an appropriate atrioventricular delay. The objectives of this study were to assess the early and long-term effects of this therapy on functional capacity and left ventricular function in patients with severe heart failure and left bundle branch block. METHODS AND RESULTS: Twelve patients with end-stage congestive heart failure, sinus rhythm and complete left bundle branch block were treated with biventricular stimulation at optimized atrioventricular delay. The NYHA functional class and maximal bicycle exercise capacity were assessed. Systolic and diastolic left ventricular function were studied with echocardiography and radionuclide angiography. Data was collected at various intervals during 1-year follow-up. Cumulative survival [95% CI] was 66.7% [40.0,93.4] at 1 year and 50 % [21.8, 78.2] at 2 and 3 years. Median NYHA class improved from class IV to class II at 1 year (p=0.008). After 6 weeks an increase in exercise capacity occurred, which was sustained. A less restrictive left ventricular filling pattern, an increase in dP/dt and left ventricular ejection fraction, and a decrease in mitral regurgitation were observed early and long-term. CONCLUSIONS: Biventricular pacing at optimized atrioventricular delay results in improvement in functional capacity, which is associated with improved systolic and diastolic left ventricular function, and a decrease in mitral regurgitation during short- and long-term follow-up.

Bundle-Branch Block↗

Reduced graft function (with or without dialysis) vs immediate graft function--a comparison of long-term renal allograft survival.

BACKGROUND: Delayed graft function (DGF) is a common complication in cadaveric kidney transplants affecting graft outcome. However, the incidence of DGF differs widely between centres as its definition is very variable. The purpose of this study was to define a parameter for DGF and immediate graft function (IGF) and to compare the graft outcome between these groups at our centre. METHODS: The renal allograft function of 972 first cadaveric transplants performed between 1990 and 2001 in the Republic of Ireland was examined. The DGF and IGF were defined by a creatinine reduction ratio (CRR) between time 0 of transplantation and day 7 post-transplantation of <70 and >70%, respectively. Recipients with reduced graft function (DGF) not requiring dialysis were defined as slow graft function (SGF) patients. The serum creatinine at 3 months, 6 months, 1, 2 and 5 years after transplantation was compared between these groups of recipients. The graft survival rates at 1, 3 and 5 years and the graft half-life for DGF, SGF and IGF recipients were also assessed. RESULTS: Of the 972 renal transplant recipients, DGF was seen in 102 (10.5%) patients, SGF in 202 (20.8%) recipients and IGF in 668 (68.7%) patients. Serum creatinine levels were significantly different between the three groups at 3 and 6 months, 1, 2 and 5 years. Graft survival at 5 years for the DGF patients was 48.5%, 60.5% for SGF recipients and 75% for IGF patients with graft half-life of 4.9, 8.7 and 10.5 years, respectively. CONCLUSION: This study has shown that the CRR at day 7 correlates with renal function up to 5 years post-transplantation and with long-term graft survival. We have also demonstrated that amongst patients with reduced graft function after transplantation, two groups with significantly different outcomes exist.

Adult↗

Airway function at one year: association with premorbid airway function, wheezing, and maternal smoking.

BACKGROUND: Impaired growth and development of the respiratory system during fetal and early postnatal life may have important implications for lung development and later lung health. The aim of this study was to examine the association of diminished premorbid airway function, prior wheezing, and maternal smoking with airway function at 1 year of age. METHODS: Respiratory function was measured at the end of the first year in 100 of 108 healthy term infants (93%) in whom similar measurements had been undertaken prior to any respiratory illness at 8 weeks. Physician diagnosed wheezing episodes were identified retrospectively from medical records. RESULTS: At 1 year specific airway conductance during end expiration (sGawEE; /s/kPa) was significantly diminished in those infants with prior wheezing (95% CI wheeze/no wheeze -0.76 to -0.14), mothers who smoked (95% CI smoke/no smoke -0.81 to -0.27), a family history of asthma (95% CI family history/no family history -0.62 to 0.00), or diminished premorbid sGawEE (95% CI -0.13 to -0.43/s/kPa per unit reduction sGawEE at 8 weeks). In a multivariate model only maternal smoking and diminished premorbid sGawEE were independently associated with diminished sGawEE at 1 year. CONCLUSIONS: Diminished airway function at the end of the first year appears to be mediated by impaired airway development during early life as well as by exposure to maternal smoking. These findings are consistent with the hypothesis that, at a population level, diminished premorbid airway function provides the link between wheezing lower respiratory illness and diminished airway function at 1 year. Maternal smoking remains an important and avoidable cause of impaired airway development and function in infancy.

Airway Resistance↗

Changes in left ventricular volume, mass, and function during the development and regression of supraventricular tachycardia-induced cardiomyopathy. Disparity between recovery of systolic versus diastolic function.

Chronic supraventricular tachycardia causes a dilated cardiomyopathy in man. Terminating this tachycardia appears to result in symptomatic improvement; however, its effects on left ventricular (LV) volume, mass, and function have not been fully examined. Accordingly, hemodynamic studies using simultaneous echocardiography and catheterization were performed in three groups of pigs: 1) those subjected to rapid left atrial pacing (240 beats/min) for 3 weeks (SVT, n = 8), 2) those subjected to supraventricular tachycardia for 3 weeks followed by termination of pacing and a 4-week recovery period (PSVT, n = 9), and 3) sham-operated controls (CTR, n = 10). Systolic pump function was assessed using fractional shortening (FS), peak ejection rate [peak (-)dD/dt], and maximum rate of pressure development [peak (+)dP/dt]. Diastolic function was assessed using the time constant of isovolumic pressure decline (tau), peak early diastolic filling rate [peak (+)dD/dt], the chamber stiffness constant (Kc), and the myocardial stiffness constant (Km). Supraventricular tachycardia caused LV dilation (end-diastolic dimension [EDD] increased from 3.5 +/- 0.4 cm in CTR to 4.9 +/- 0.5 cm in SVT, p less than 0.05) but no change in LV mass (LV weight-to-body weight ratio [LV/BW]) was 2.58 +/- 0.3 g/kg in CTR and 2.66 +/- 0.4 g/kg in SVT), all indexes of systolic function became abnormal (FS fell from 30 +/- 4% in CTR to 13 +/- 5% in SVT, p less than 0.05), and the indexes of relaxation and filling were slowed (tau increased from 36 +/- 3 msec in CTR to 51 +/- 13 msec in SVT, p less than 0.05). There were no significant changes in Kc or Km. After terminating the supraventricular tachycardia, LV volume fell but remained greater than that in CTR (EDD was 4.2 +/- 0.4 cm in PSVT, p less than 0.05 versus CTR) and substantial LV hypertrophy developed (LV/BW was 3.48 +/- 0.5 g/kg in PSVT, p less than 0.05 versus CTR). Systolic function returned to normal (FS was 31 +/- 5% in PSVT) but diastolic function remained abnormal. In PSVT, tau remained prolonged (49 +/- 12 msec, p less than 0.05 versus CTR), Kc increased from 3.7 +/- 1.0 in CTR to 7.4 +/- 1.2 (p less than 0.05), and Km increased from 4.4 +/- 1.5 in CTR to 13.9 +/- 9.7 (p less than 0.05). Thus, the improvement in systolic function that occurs after the termination of supraventricular tachycardia is associated with the development of LV hypertrophy and persistent diastolic dysfunction.

Animals↗

[Function scintigraphy: a uniform method for quantifying organ metabolism and function].

Functional scintigraphy is a quantitative method with which metabolic parameters of an organ can be determined by measuring the time activity course of a radioactive tracer in tissue. Their quantitative value is, however, limited by inherent sources of error, e.g. the absorption of radiation in the organ or overlapping of fore- and background activities. Hitherto, existing procedures for calculation of metabolic parameters are based more on given technical possibilities than on common theoretical foundations. They are notable for their variety in methodical approach, frequently being of empirical character. Quantitative results from different institutes and hospitals can therefore rarely be compared. The present work describes a methodical approach to obtain comparable methods in nuclear medicine, by including the pharmacokinetics of a tracer in blood. This leads to the compartment analysis (deterministic) or to a stochastic (non-deterministic) description of the kinetics in an organ. The stochastic description requires the calculation of the linear response function from a convolution integral. By means of functional analytical methods a mathematical procedure has been developed which for the first time permits the calculation of the linear response function in each pixel and at any time of the study. Easily readable functional images show how relevant parameters can be calculated from the linear response function. Due to its independence on any model, the linear response function enables furthermore a regional investigation of existing or new compartment models of tracer kinetics in the organ concerned.

Bone and Bones↗

Right ventricular functional recovery after acute myocardial infarction: relation with left ventricular function and interventricular septum motion. GISSI-3 echo substudy.

OBJECTIVE: To evaluate the pattern of right ventricular (RV) functional recovery and its relation with left ventricular (LV) function and interventricular septal (IVS) motion in low risk patients after acute myocardial infarction (AMI). DESIGN AND SETTING: Multicentre clinical trial carried out in 47 Italian coronary care units. PATIENTS: 500 patients from the GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) -3 echo substudy, who underwent serial echocardiograms 24-48 hours after symptom onset and at discharge, six weeks, and six months after AMI. RESULTS: Tricuspid annular plane systolic excursion (TAPSE) increased significantly during follow up (mean (SD) 1.79 (0.46) cm at 24-48 hours to 1.92 (0.46) cm at six months, p < 0.001) and the increase was already significant at discharge (1.88 (0.47) cm, p < 0.001). LV ejection fraction (LVEF) was the best correlate of TAPSE at 24-48 hours (r = 0.15, p = 0.001). TAPSE increased significantly in patients both with reduced (< 45%) and with preserved (> or = 45%) LVEF, but the magnitude of increase was higher in patients with lower initial LVEF (p = 0.001). Improvement in IVS wall motion score index (IVS-WMSI) was the only independent predictor of TAPSE changes during follow up (r = -0.12, p = 0.007). CONCLUSIONS: In low risk patients after AMI, RV function recovered throughout six months of follow up and was already significant at discharge. TAPSE was significantly related to LVEF at 24-48 hours. The magnitude of RV functional recovery was higher in patients with lower initial LVEF. RV functional recovery is best related to IVS-WMSI improvement, suggesting that IVS motion has an important role in RV functional improvement in this setting.

Adult↗

Large-scale prediction of function shift in protein families with a focus on enzymatic function.

Protein function shift can be predicted from sequence comparisons, either using positive selection signals or evolutionary rate estimation. None of the methods have been validated on large datasets, however. Here we investigate existing and novel methods for protein function shift prediction, and benchmark the accuracy against a large dataset of proteins with known enzymatic functions. Function change was predicted between subfamilies by identifying two kinds of sites in a multiple sequence alignment: Conservation-Shifting Sites (CSS), which are conserved in two subfamilies using two different amino acid types, and Rate-Shifting Sites (RSS), which have different evolutionary rates in two subfamilies. CSS were predicted by a new entropy-based method, and RSS using the Rate-Shift program. In principle, the more CSS and RSS between two subfamilies, the more likely a function shift between them. A test dataset was built by extracting subfamilies from Pfam with different EC numbers that belong to the same domain family. Subfamilies were generated automatically using a phylogenetic tree-based program, BETE. The dataset comprised 997 subfamily pairs with four or more members per subfamily. We observed a significant increase in CSS and RSS for subfamily comparisons with different EC numbers compared to cases with same EC numbers. The discrimination was better using RSS than CSS, and was more pronounced for larger families. Combining RSS and CSS by discriminant analysis improved classification accuracy to 71%. The method was applied to the Pfam database and the results are available at http://FunShift.cgb.ki.se. A closer examination of some superfamily comparisons showed that single EC numbers sometimes embody distinct functional classes. Hence, the measured accuracy of function shift is underestimated.

Amino Acid Sequence↗

Functional data analysis with application to periodically stimulated foetal heart rate data. I: functional regression.

Functional regression is used to model longitudinal data where the number of measurements on the functional covariate is much greater than the number of subjects in the study. Thus, functional regression can be thought of as singular longitudinal analysis. We have modified existing functional regression techniques to the case of a functional covariate with a repeated stimulus. We applied this modified functional regression to periodically stimulated foetal heart rates. The heart rate tracings were used as a predictor of the child's psychomotor development at approximately 18 months of age. In the past, this type of data has been analysed using the partially subjective concept of habituation. By using the entire heart rate tracings through functional regression, we have the advantage that habituation does not need to be defined and all available information is used to predict later child development.

Adult↗