Browsing by Subject "POSITION"

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  • Zhou, Kecheng; Dichlberger, Andrea; Martinez-Seara, Hector; Nyholm, Thomas K. M.; Li, Shiqian; Kim, Young Ah; Vattulainen, Ilpo; Ikonen, Elina; Blom, Tomas (2018)
    Membrane proteins are functionally regulated by the composition of the surrounding lipid bilayer. The late endosomal compartment is a central site for the generation of ceramide, a bioactive sphingolipid, which regulates responses to cell stress. The molecular interactions between ceramide and late endosomal transmembrane proteins are unknown. Here, we uncover in atomistic detail the ceramide interaction of Lysosome Associated Protein Transmembrane 4B (LAPTM4B), implicated in ceramide-dependent cell death and autophagy, and its functional relevance in lysosomal nutrient signaling. The ceramide-mediated regulation of LAPTM4B depends on a sphingolipid interaction motif and an adjacent aspartate residue in the protein's third transmembrane (TM3) helix. The interaction motif provides the preferred contact points for ceramide while the neighboring membrane-embedded acidic residue confers flexibility that is subject to ceramide-induced conformational changes, reducing TM3 bending. This facilitates the interaction between LAPTM4B and the amino acid transporter heavy chain 4F2hc, thereby controlling mTORC signaling. These findings provide mechanistic insights into how transmembrane proteins sense and respond to ceramide.
  • Turc, L.; Fontaine, D.; Savoini, P.; Hietala, H.; Kilpua, E. K. J. (2013)
  • Kivimäki, Mika; Batty, G David; Pentti, Jaana; Shipley, Martin J; Sipilä, Pyry N; Nyberg, Solja T; Suominen, Sakari B; Oksanen, Tuula; Stenholm, Sari; Virtanen, Marianna; Marmot, Michael G; Singh-Manoux, Archana; Brunner, Eric J; Lindbohm, Joni V; Ferrie, Jane E; Vahtera, Jussi (2020)
    Summary Background Socioeconomic disadvantage is a risk factor for many diseases. We characterised cascades of these conditions by using a data-driven approach to examine the association between socioeconomic status and temporal sequences in the development of 56 common diseases and health conditions. Methods In this multi-cohort study, we used data from two Finnish prospective cohort studies: the Health and Social Support study and the Finnish Public Sector study. Our pooled prospective primary analysis data comprised 109 246 Finnish adults aged 17–77 years at study entry. We captured socioeconomic status using area deprivation and education at baseline (1998–2013). Participants were followed up for health conditions diagnosed according to the WHO International Classification of Diseases until 2016 using linkage to national health records. We tested the generalisability of our findings with an independent UK cohort study—the Whitehall II study (9838 people, baseline in 1997, follow-up to 2017)—using a further socioeconomic status indicator, occupational position. Findings During 1 110 831 person-years at risk, we recorded 245 573 hospitalisations in the Finnish cohorts; the corresponding numbers in the UK study were 60 946 hospitalisations in 186 572 person-years. Across the three socioeconomic position indicators and after adjustment for lifestyle factors, compared with more advantaged groups, low socioeconomic status was associated with increased risk for 18 (32·1%) of the 56 conditions. 16 diseases formed a cascade of inter-related health conditions with a hazard ratio greater than 5. This sequence began with psychiatric disorders, substance abuse, and self-harm, which were associated with later liver and renal diseases, ischaemic heart disease, cerebral infarction, chronic obstructive bronchitis, lung cancer, and dementia. Interpretation Our findings highlight the importance of mental health and behavioural problems in setting in motion the development of a range of socioeconomically patterned physical illnesses. Policy and health-care practice addressing psychological health issues in social context and early in the life course could be effective strategies for reducing health inequalities. Funding UK Medical Research Council, US National Institute on Aging, NordForsk, British Heart Foundation, Academy of Finland, and Helsinki Institute of Life Science.
  • Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Sinilnikova, Olga M.; Healey, Sue; McGuffog, Lesley; Mazoyer, Sylvie; Chenevix-Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.; Nathanson, Katherine L.; CIMBA Consortium; Nevanlinna, Heli; Aittomäki, Kristiina (2015)
    IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317(12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682(6%) with ovarian cancer, 272(2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% Cl, 1.22-1.74; P = 2 x 10(-6)), c.4328 to c.4945 (BCCR2; RH R = 1.34; 95% Cl, 1.01-1.78; P =.04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% Cl, 1.22-1.55; P = 6 x 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% Cl, 0.56-0.70; P = 9 x 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% Cl, 1.06-2.78; P =.03), c.772 to c.1806 (BCCRI; RHR = 1.63; 95% Cl, 1.10-2.40; P =.01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% Cl, 1.69-3.16; P =.00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% Cl, 0.44-0.60; P = 6 x 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% Cl, 0.41-0.80; P =.001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.
  • Kwak, Gloria Hyunjung; Kwak, Eun-Jung; Song, Jae Min; Park, Hae Ryoun; Jung, Yun-Hoa; Cho, Bong-Hae; Hui, Pan; Hwang, Jae Joon (2020)
    The practicability of deep learning techniques has been demonstrated by their successful implementation in varied fields, including diagnostic imaging for clinicians. In accordance with the increasing demands in the healthcare industry, techniques for automatic prediction and detection are being widely researched. Particularly in dentistry, for various reasons, automated mandibular canal detection has become highly desirable. The positioning of the inferior alveolar nerve (IAN), which is one of the major structures in the mandible, is crucial to prevent nerve injury during surgical procedures. However, automatic segmentation using Cone beam computed tomography (CBCT) poses certain difficulties, such as the complex appearance of the human skull, limited number of datasets, unclear edges, and noisy images. Using work-in-progress automation software, experiments were conducted with models based on 2D SegNet, 2D and 3D U-Nets as preliminary research for a dental segmentation automation tool. The 2D U-Net with adjacent images demonstrates higher global accuracy of 0.82 than naïve U-Net variants. The 2D SegNet showed the second highest global accuracy of 0.96, and the 3D U-Net showed the best global accuracy of 0.99. The automated canal detection system through deep learning will contribute significantly to efficient treatment planning and to reducing patients’ discomfort by a dentist. This study will be a preliminary report and an opportunity to explore the application of deep learning to other dental fields.
  • Mustikka, Minna P.; Pietilä, Elina M.; Mykkanen, Anna K.; Gronthal, Thomas S. C. (2020)
    Objective: To obtain a reference range for evaluation of intraocular pressure (IOP) in horses using Tonovet Plus (R), to compare the IOP readings obtained with Tonovet (R) and Tonovet Plus (R), and to evaluate the repeatability of readings. Animals studied and Procedures: Intraocular pressure of 30 client-owned horses (60 eyes) with no signs of illness or ocular disease was evaluated using Tonovet (R) and Tonovet Plus (R) rebound tonometers. Horses' mean age was 10.7 (range 6-17) years. Triplicate measurements were performed without using sedatives or local anesthetics, with minimal restraint. Results: Calculated reference intervals (the CLSI robust method) were 14.4-27.2 mmHg for Tonovet (R) and 16.0-26.1 mmHg for Tonovet Plus (R). Mean values (+/- standard deviation, SD [+/- coefficient of variation, CV]) obtained with Tonovet Plus (R)(21.6 +/- 2.45 mmHg [11.3%]) were on average 0.6 mmHg higher than with Tonovet (R)(21.0 +/- 3.14 mmHg [15.0%]), and a negligible statistical difference between the devices was found using the paired sample t test (P = .049). The correlation coefficient for the averaged triplicate measurements was 0.73. The average CV was 4.6% and 4.4% for Tonovet (R) and Tonovet Plus (R), respectively. Conclusions: The repeatability of measurements was very good with both devices. The readings between the two devices differed statistically significantly, but the correlation was considered good and the variation was numerically small, and thus, the difference was considered clinically irrelevant. When monitoring disease process or treatment response in an individual patient, repeated readings are best performed using a similar device to avoid false interpretation of results.
  • Knowler, Susan P.; Kiviranta, Anna-Mariam; McFadyen, Angus K.; Jokinen, Tarja S.; La Ragione, Roberto M.; Rusbridge, Clare (2017)
    Objectives To characterize and compare the phenotypic variables of the hindbrain and craniocervical junction associated with syringomyelia (SM) in the Chihuahua, Affenpinscher and Cavalier King Charles Spaniel (CKCS). Method Analysis of 273 T1-weighted mid-sagittal DICOM sequences of the hindbrain and craniocer-vical junction from 99 Chihuahuas, 42 Affenpinschers and 132 CKCSs. The study compared 22 morphometric features (11 lines, eight angles and three ratios) of dogs with and without SM using refined techniques based on previous studies of the Griffon Bruxellois (GB) using Discriminant Function Analysis and ANOVA with post-hoc corrections. Results The analysis identified 14/22 significant traits for SM in the three dog breeds, five of which were identical to those reported for the GB and suggest inclusion of a common aetiology. One ratio, caudal fossa height to the length of the skull base extended to an imaginary point of alignment between the atlas and supraoccipital bones, was common to all three breeds (p values 0.029 to <0.001). Associated with SM were a reduced occipital crest and two acute changes in angulation i) 'sphenoid flexure' at the spheno-occipital synchondrosis ii) 'cervical flexure' at the foramen magnum allied with medulla oblongata elevation. Comparing dogs with and without SM, each breed had a unique trait: Chihuahua had a smaller angle between the dens, atlas and basioccipital bone (p value <0.001); Affenpinschers had a smaller dis-tance from atlas to dens (p value 0.009); CKCS had a shorter distance between the spheno-occipital synchondrosis and atlas (p value 0.007). Conclusion The selected morphometries successfully characterised conformational changes in the brain and craniocervical junction that might form the basis of a diagnostic tool for all breeds. The severity of SM involved a spectrum of abnormalities, incurred by changes in both angulation and size that could alter neural parenchyma compliance and/or impede cerebrospinal fluid channels.
  • Vandenheede, Hadewijch; Deboosere, Patrick; Espelt, Albert; Bopp, Matthias; Borrell, Carme; Costa, Giuseppe; Eikemo, Terje Andreas; Gnavi, Roberto; Hoffmann, Rasmus; Kulhanova, Ivana; Kulik, Margarete; Leinsalu, Mall; Martikainen, Pekka; Menvielle, Gwenn; Rodriguez-Sanz, Maica; Rychtarikova, Jitka; Mackenbach, Johan P.; EURO-GBD-SE Consortium (2015)
    To evaluate educational inequalities in diabetes mortality in Europe in the 2000s, and to assess whether these inequalities differ between genders. Data were obtained from mortality registries covering 14 European countries. To determine educational inequalities in diabetes mortality, age-standardised mortality rates, mortality rate ratios, and slope and relative indices of inequality were calculated. To assess whether the association between education and diabetes mortality differs between genders, diabetes mortality was regressed on gender, educational rank and 'gender x educational rank'. An inverse association between education and diabetes mortality exists in both genders across Europe. Absolute educational inequalities are generally larger among men than women; relative inequalities are generally more pronounced among women, the relative index of inequality being 2.8 (95 % CI 2.0-3.9) in men versus 4.8 (95 % CI 3.2-7.2) in women. Gender inequalities in diabetes mortality are more marked in the highest than the lowest educated. Education and diabetes mortality are inversely related in Europe in the 2000s. This association differs by gender, indicating the need to take the socioeconomic and gender dimension into account when developing public health policies.
  • Chen, Chi-Chuan; Hyvönen, Jaakko; Schneider, Harald (2020)
    The microsoroid ferns are one of the largest subfamilies of the Polypodiaceae with over 180 species mainly found in the humid forests of tropical Australasia. The phylogenetic relationships are still unclear, especially the delimitation of the genus Microsorum which has been recognized to be non-monophyletic. We analysed the microsoroid ferns using six chloroplast DNA regions (rbcL, rps4+rps4-trnS, trnL+trnL-trnF, atpA, atpB and matK) in order to present a robust hypothesis of their phylogeny. Our results suggest that they comprise up to 17 genera; of them, 12 agree with a previously accepted generic classification. Five tribes are proposed based on the phylogenetic relationships. Most of the species traditionally included in the genus Microsorum are found in six genera belonging to two tribes. In addition to the commonly used DNA markers, the additional atpA and matK are helpful to provide information about the phylogenetic relationships of the microsoroid ferns.
  • Rönö, K.; Masalin, S.; Kautiainen, H.; Gissler, M.; Raina, M.; Eriksson, J. G.; Laine, M. K. (2019)
    Aims Findings concerning the impact of socio-economic status on the risk of gestational diabetes mellitus (GDM) are inconclusive and little is known about the simultaneous impact of income and educational attainment on the risk of GDM. This study aims to assess the impact of maternal prepregnancy income in combination with traditional GDM risk factors on the incidence of GDM in primiparous women. Methods This is an observational cohort study including 5962 Finnish women aged >= 20 years from the city of Vantaa, Finland, who delivered for the first time between 2009 and 2015, excluding women with pre-existing diabetes mellitus. The Finnish Medical Birth Register, Finnish Tax Administration, Statistics Finland, Social Insurance Institution of Finland and patient healthcare records provided data for the study. We divided the study population according to five maternal income levels and four educational attainment levels. Results Incidence of GDM decreased with increasing income level in primiparous women (P <0.001 for linearity, adjusted for smoking, age, BMI and cohabiting status). In an adjusted two-way model, the relationship was significant for both income (P = 0.007) and education (P = 0.039), but there was no interaction between income and education (P = 0.52). Conclusions There was an inverse relationship between both maternal prepregnancy taxable income and educational attainment, and the risk of GDM in primiparous Finnish women.
  • Zhang, PeiJin; Zucca, Pietro; Sridhar, Sarrvesh Seethapuram; Wang, ChuanBing; Bisi, Mario M.; Dabrowski, Bartosz; Krankowski, Andrzej; Mann, Gottfried; Magdalenic, Jasmina; Morosan, Diana E.; Vocks, Christian (2020)
    Context. Solar radio bursts originate mainly from high energy electrons accelerated in solar eruptions like solar flares, jets, and coronal mass ejections. A sub-category of solar radio bursts with short time duration may be used as a proxy to understand wave generation and propagation within the corona.Aims. Complete case studies of the source size, position, and kinematics of short term bursts are very rare due to instrumental limitations. A comprehensive multi-frequency spectroscopic and imaging study was carried out of a clear example of a solar type IIIb-III pair.Methods. In this work, the source of the radio burst was imaged with the interferometric mode, using the remote baselines of the LOw Frequency ARray (LOFAR). A detailed analysis of the fine structures in the spectrum and of the radio source motion with imaging was conducted.Results. The study shows how the fundamental and harmonic components have a significantly different source motion. The apparent source of the fundamental emission at 26.56 MHz displaces away from the solar disk center at about four times the speed of light, while the apparent source of the harmonic emission at the same frequency shows a speed of <0.02 c. The source size of the harmonic emission observed in this case is smaller than that in previous studies, indicating the importance of the use of remote baselines.
  • Sumanen, Hilla; Pietilainen, Olli; Lahti, Jouni; Lahelma, Eero; Rahkonen, Ossi (2015)
    Background: A low socioeconomic position (SEP) is consistently associated with ill health, sickness absence (SA) and permanent disability, but studies among young employees are lacking. We examined the interrelationships between education, occupational class and income as determinants of SA among 25-34-year-old employees. We also examined, whether the association between SEP and SA varied over time in 2002-2007 and 2008-2013. Methods: The analyses covered young, 25-34-year-old women and men employed by the City of Helsinki over the time periods 2002-2007 and 2008-2013. Four-level education and occupational class classifications were used, as well as income quartiles. The outcome measure was the number of annual SA days. Results: Education had the strongest and most consistent independent association with SA among women and men in both periods under study. Occupational class had weaker independent and less consistent association with SA. Income had an independent association with SA, which strengthened over time among the men. The interrelationships between the SEP indicators and SA were partly explained by prior or mediated through subsequent SEP indicators. Socioeconomic differences followed only partially a gradient for occupational class and also for income among men. Conclusions: Preventive measures to reduce the risk of SA should be considered, especially among young employees with a basic or lower-secondary education.
  • Raatevaara, Antti; Korpunen, Heikki; Mäkinen, Harri; Uusitalo, Jori (2020)
    In cut-to-length logging, the harvester operator adjusts the bucking in accordance with visible defects on processed stems. Some of the defects, such as a sweep on the bottom of the stem, decrease the yield and quality of sawn products and are difficult for the operator to notice. Detecting the defects with improved sensors would support the operator in his qualitative decision-making and increase value recovery of logging. Predicting the maximum bow height of the bottom log in Norway spruce (Picea abies (L.) Karst.) with log end face image and stem taper was investigated with two modelling approaches. A total of 101 stems were selected from five clear-cut stands in southern Finland. The stems were crosscut and taper measured, and the butt ends of the bottom logs were photographed. The stem diameter, out-of-roundness, and pith eccentricity were measured from the images while the max. bow height was measured by a 3D log scanner at a sawmill. The bottom logs with an eccentric pith had higher max. bow height. In addition, a highly conical bottom part of the stem was more common on the bottom logs with a large max. bow height. Applying both log end face image and stem taper measurements gave the best model fit and detection accuracy (76%) for bottom logs with a large max. bow height. The results indicate that the log end face image and stem taper measurements can be utilised to aid harvester operator in deciding an optimised length for logs according to the bow height.
  • Toivonen, Jarkko; Das, Pratyush; Taipale, Jussi; Ukkonen, Esko (2020)
    Motivation: Position-specific probability matrices (PPMs, also called position-specific weight matrices) have been the dominating model for transcription factor (TF)-binding motifs in DNA. There is, however, increasing recent evidence of better performance of higher order models such as Markov models of order one, also called adjacent dinucleotide matrices (ADMs). ADMs can model dependencies between adjacent nucleotides, unlike PPMs. A modeling technique and software tool that would estimate such models simultaneously both for monomers and their dimers have been missing. Results: We present an ADM-based mixture model for monomeric and dimeric TF-binding motifs and an expectation maximization algorithm MODER2 for learning such models from training data and seeds. The model is a mixture that includes monomers and dimers, built from the monomers, with a description of the dimeric structure (spacing, orientation). The technique is modular, meaning that the co-operative effect of dimerization is made explicit by evaluating the difference between expected and observed models. The model is validated using HT-SELEX and generated datasets, and by comparing to some earlier PPM and ADM techniques. The ADM models explain data slightly better than PPM models for 314 tested TFs (or their DNA-binding domains) from four families (bHLH, bZIP, ETS and Homeodomain), the ADM mixture models by MODER2 being the best on average.
  • Loman, Tina; Lallukka, Tea; Laaksonen, Mikko; Rahkonen, Ossi; Lahelma, Eero (2013)
  • Toch-Marquardt, Marlen; Menvielle, Gwenn; Eikemo, Terje A.; Kulhanova, Ivana; Kulik, Margarete C.; Bopp, Matthias; Esnaola, Santiago; Jasilionis, Domantas; Maki, Netta; Martikainen, Pekka; Regidor, Enrique; Lundberg, Olle; Mackenbach, Johan P.; Euro-GBD-SE Consortium (2014)
  • Halonen, Jaana I.; Vahtera, Jussi; Oksanen, Tuula; Pentti, Jaana; Virtanen, Marianna; Jokela, Markus; Diez-Roux, Ana V.; Kivimäki, Mika (2013)
  • Kurki, Ilmari; Hyvärinen, Aapo; Saarinen, Jussi (2016)
    We studied how learning changes the processing of a low-level Gabor stimulus, using a classification-image method (psychophysical reverse correlation) and a task where observers discriminated between slight differences in the phase (relative alignment) of a target Gabor in visual noise. The method estimates the internal "template" that describes how the visual system weights the input information for decisions. One popular idea has been that learning makes the template more like an ideal Bayesian weighting; however, the evidence has been indirect. We used a new regression technique to directly estimate the template weight change and to test whether the direction of reweighting is significantly different from an optimal learning strategy. The subjects trained the task for six daily sessions, and we tested the transfer of training to a target in an orthogonal orientation. Strong learning and partial transfer were observed. We tested whether task precision (difficulty) had an effect on template change and transfer: Observers trained in either a high-precision (small, 608 phase difference) or a low-precision task (1808). Task precision did not have an effect on the amount of template change or transfer, suggesting that task precision per se does not determine whether learning generalizes. Classification images show that trainingmade observers use more task-relevant features and unlearn some irrelevant features. The transfer templates resembled partially optimized versions of templates in training sessions. The template change direction resembles ideal learning significantly but not completely. The amount of template change was highly correlated with the amount of learning.
  • Molander, Pauliina; Jussila, Airi; Toivonen, Tanja; Makkeli, Pauliina; Alho, Antti; Kolho, Kaija-Leena (2018)
    Introduction: A specialized inflammatory bowel disease (IBD) nurse is considered a valuable and cost-effective member of a multidisciplinary team, not all clinics responsible for IBD care employ such nurses. We evaluated IBD nurse resources, quality of care and cost effects on IBD patients care in a nationwide study in Finland. Methods: A healthcare professional electronic survey was conducted in order to assess the impact of an IBD nurse on the quality of care. To study the cost effects, we obtained nationwide comprehensive data covering years between 2008 and 2016 from major administrative healthcare districts of Finland. Patients with a diagnosis of IBD (ICD-code K50 or K51) were identified from the data and their personal contacts and hospitalization were analyzed. The results were compared between healthcare districts with an IBD nurse and healthcare districts without an IBD nurse. Results: Forty-nine physicians and 88 nurses responded to the survey. Of the physicians, 92% reported that an established IBD nurse had released physician's resources. The most important IBD nurse contributions listed were patient support and follow-up (79-81% of the respondents). Healthcare district, which had an established IBD nurse, produced more patient contacts. A larger proportion of the contacts was managed by the IBD nurse. Clinics with an IBD nurse reported less patient hospitalization (4-9% vs 11-19%, p <.001). Estimated annual cost savings while employing an IBD nurse may be significant. Conclusion: The introduction of an IBD nurse led to better quality of care and potentially significant cost savings by reducing hospitalization rates and reallocating physician's time resources.