Nonetheless, a recent case of BO/OP in a boy LY3009104 was associated with a severe immune reaction to Mycoplasma pneumoniae infection [24]. The cryptogenic (undefined aetiology or idiopathic presentations of OP) actually the most relevant form of OP (also called primary OP or COP) [10�C12, 31] is excluded in this work for comparative purposes.Typical fibrinous or fibrinosuppurative pneumonias in feedlot cattle are characterised by accumulation of exudates in the alveolar spaces and bronchioles. Organization of this material is one of the most conspicuous images of the pneumonic lesion in calves, which died during severe M. haemolytica pneumonia [9]. Organising exudates consist of whorls of fibrin admixed with streaming neutrophils (oat cells) inside alveoli and bronchioles [32].

As has been noted, resolution of the lesions in severe cases is incomplete and evolves toward organisation from fibrinous to fibrous plugs covered by type II pneumocytes [26] (Figures 1(a), 1(c), and 1(d)). Experimentally, this change has been seen by 15 days post inoculation and beyond in a model of progression of lung lesions referred in sheep [6]. Therefore, lesions described in BO/OP due to bacterial infections, such as Streptococcus pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila, and Pseudomonas aeruginosa [9�C12], are similar to those observed in chronic cases of exudative pneumonias (fibrinosuppurative bronchopneumonias) in feedlot cattle. The lobar distribution of BO/OP [10�C12] is also in accordance with the pneumonic lesions found in shipping fever [9].

It was postulated that development of BO/OP lesions induced in mice is the result of the severity of initial lung injury inciting an augmented expression of proinflammatory and profibrotic cytokines [33]. This condition is likely to occur in severe cases of shipping fever pneumonia, considering the concomitant role of M. bovis and continuous exposure to environmental pollutants in the feedlot, which contribute to/or sustain the inflammatory response with progression to fibroplasia [1, 22, 34, 35].It is worth to mention that recently the chronic lung lesions recognized in pigs naturally infected with porcine circovirus 2 (disease named chronic postweaning multisystemic wasting syndrome [PMWS]) showed similarities with BO/OP [36].4.

Bronchiolar Involvement as a Result of Large Airway DiseaseArising Brefeldin_A from virus-induced bronchiolar insult, air pollution and lipopolysaccharide (LPS) may also instigate the severity and permanence of chronic inflammation with or without bacterial superinfection. For instance, higher morbidity and more severe cases of RSV occur in infants living in zones with high levels of air pollution [18�C20]. Correspondingly, the highest morbidity and mortality related to respiratory viral infections occur in younger calves entering the feedlot pen [1].

Hydrated XD has properties similar to those of normal human skin.Figure 2The effect of XD compared to antibacterial cream Flammazine in a patient burned by acetone steam (deep dermal burn). An example selleck Lenalidomide of XD healing effect. (a) Day 1: the burn wound on the leg at the initiation of treatment. (b) XD was applied to the distal …The aim of the current study was to gain more insight into the biological mechanism of XD-mediated wound healing. The bioactivity of XD has been demonstrated in a cell culture assay. Keratinocyte growth and differentiation in vitro on XD and in vivo under XD was analyzed by histology and immunocytochemistry. Our hypothesis was that the natural biological structure of the dermis plays an important role in proliferation and differentiation of the patient’s own keratinocytes.

2. Material and MethodsWe analyzed growth and differentiation of primary human keratinocytes cultured in vitro on XD. We then compared the results with differentiation of neoepidermis in a freshly healing wound treated with XD. Proliferation and differentiation of skin cells in vitro and in the deep dermal burn wound covered with XD was compared using routine histological and immunohistological methods.2.1. Tensile Strength of XDTensile testing on bone-shaped samples was conducted on the testing engine INSPEKT desk 10kN (Hegewald & Peschke) equipped with programme Labmaster. Samples were hydrated overnight in PBS and pulled to failure at 100mm/min using a mechanical stand with a 100N load cell. In total, 40 samples of XD were measured.2.2.

Keratinocyte Cultivation on XDHuman primary keratinocytes (2nd passage) were obtained from redundant skin of donors undergoing abdominoplasty. Keratinocytes were cultured on XD using the 3T3 feeder layer technique [6, 12]. Prior to seeding the cells, XD in the tissue culture dish was immersed in a standard culture medium (HMEM with non-essential amino acids, 0.12g/L sodium pyruvate, 1g/L NaHCO3, and 10% bovine serum) overnight at 37��C. Lethally irradiated NIH-3T3 cells were used as feeder cells and were seeded on the dish with XD at a concentration of 3 �� 104cells/cm2 in a standard culture medium. On the following day, the keratinocytes were seeded at a concentration of 5 �� 104cells/cm2 in a standard culture medium enriched with 2% fetal bovine serum, hydrocortisone (0.5ug/mL), insulin (0.12U/mL), cholera toxin (10?10M), and EGF (5ng/mL).

The cultures were grown in a humidified 3.5% CO2 atmosphere. The progress of cell growth on XD was followed on the noncovered areas of the dish or on specimens stained by May-Gr��nwald and Giemsa-Romanowski.After achieving confluence, XD, along with 1-2 keratinocyte layers, was cut into pieces of approximately 1cm2 and lifted to the air-liquid interface on a stainless steel grid covered Drug_discovery with two layers of sterile gauze.

05 was used throughout all statistical tests in the study.3. Results3.1. Patient Characteristics and Histological SubtypesThe clinical characteristics of the 79 patients are shown in Table 1. There were except 38 males and 41 females with a mean age of 55.2 (range 16�C82) years. Regarding immunohistochemistry, the B-cell phenotype was shown in 69 specimens (87.3%), and 10 tissue specimens (12.7%) expressed the T-cell phenotype.Table 1Initial characteristics of 79 patients with de novo NHL.3.2. Serum VEGF and bFGF at the Time of DiagnosisAt the time of diagnosis, the serum VEGF concentrations from the 79 patients ranged from 72.0 to 2919.4pg/mL with a mean of 668.0pg/dL, median of 516.0pg/mL, and the third quartile of 835.5pg/mL. The serum bFGF concentration ranged from undetectable to 2919.

4pg/mL with a mean of 12.15pg/dL, median of 9.85pg/mL, and third quartile of 17.60pg/mL. Associations between serum VEGF and bFGF and clinical features at diagnosis were analyzed using mean, median, and the third quartile of both angiogenetic factors as a cut-off value. No significant associations were found (data not shown). 3.3. Prediction of Response Rate by Serum VEGF and bFGFFrom a univariate analyses, the higher levels of serum VEGF and bFGF using the mean, median, and third quartile of both angiogenetic factors as cut-off values were not associated with a poorer complete remission (CR) rate. However, patients with B symptoms, bulky diseases, anemia, poorer performance status, high serum LDH, and T-cell immunophenotype had lower CR rates. Considering the chemotherapy regimens, CHOP and R-CHOP showed higher CR rates.

Multivariate analysis identified higher than the mean of serum VEGF, B symptoms, bulky diseases, anemia, and treatment with CHOP or R-CHOP as independent variables influencing CR rate (Table 2). Table 2Univariate and multivariate analysis for complete response and overall survival.3.4. Prediction of Survival Rate by Serum VEGF and bFGFThe median follow-up time was 15.1 (range 0.3�C55.2) months. In univariate survival analyses, there was no association between serum VEGF and OS (Figure 1(a)).Figure 1(a) Overall survival by mean VEGF (b) Overall survival by mean bFGF. However, there was a significant association between shorter OS and B symptoms, more extranodal involvements, poor performance status, anemia, high serum LDH, bFGF (Figure 1(b)), and IPI.

In contrast, the CHOP or R-CHOP regimens were predictors for better OS. From a Cox proportional hazards model, variables independently associated with OS were BM involvement, more extranodal involvement, poor performance status, anemia, and higher than the mean of serum bFGF as shown in Table 2.4. DiscussionIn this study, a high pretreatment Carfilzomib level of serum VEGF and bFGF were independently associated with poorer CR and OS rates, respectively.

Meanwhile, water quality models were combined with watershed models to consider nonpoint source pollution input as a variable [42, 43]. The effects of sediments were coped with inner interaction processes of the models [43]; so, the sediment fluxes could vary accordingly under different input conditions. Therefore, the water quality management policies were greatly improved due to more constraint conditions and nonpoint source pollution simulation at watershed scale. The typical models including QUAL models [18, 19], MIKE11 model [22], and WASP models [23, 44] were developed and used at this stage. Meanwhile, the one-dimensional OTIS model developed by USGS was also applied to water quality simulation [45, 46]. 2.3. The Deepening Stage (after 1995)Nonpoint source pollution has been reduced due to strong control in developed countries. However, the dry and wet atmospheric deposition such as organic compounds, heavy metals, and nitrogen compounds showed increasing effects on water quality of rivers [47�C49]. Although nutrients and toxic chemical materials depositing to water surface have been included in model framework, these materials not only deposited directly on water surface but also they can be deposited on the land surface of a watershed and sequentially transferred to water body [20, 50], which has been an important pollutant source. From the viewpoint of management demands, an air pollution model has to be developed to introduce this proceed in the model, indicating that the static or dynamic atmospheric deposition should be related to a given watershed [51]. Therefore, at this stage, some air pollution models were integrated to water quality models to evaluate directly the contribution of atmospheric pollutant deposition [20]. With the exception of the typical models such as QUAL 2K model [52], WASP 6 model [24], QUASAR model [25, 53], SWAT model [21], and MIKE 21 [26] and MIKE 31 models [27] (Table 1), other water quality models have also been developed to simulate complicated water environmental conditions. For example, Whitehead et al. [54] developed a semidistributed integrated nitrogen model (INCA) based on the effects of atmospheric and soil N inputs, land uses, and hydrology. More recently, Fan et al. [55] integrated QUAL 2K water quality model and HEC-RAS model to simulate the impact of tidal effects on water quality simulation. For the integration of point and nonpoint sources, the US Environmental Protection Agency (USEPA) developed a multipurpose environmental analysis system (BASINS), which makes it possible to assess quickly large amounts of point and nonpoint source [28]. Meanwhile, the USEPA also listed the EFDC model as a tool for water quality management.Table 1Main surface water quality models and their versions and characteristics.

Consequently, suitable approaches to understanding the complex needs of these adult patient groups are warranted.Diagnosis of ASD is based on a qualitative impairment of social interaction and communication as well as restricted repetitive and stereotyped patterns of behavior, interest, selleck bio and activities [3]. ADHD diagnosis is characterised by attention deficits and/or hyperactivity and impulsivity. Importantly, diagnosis of each of these syndromes requires that the symptoms begin in childhood [3]. Although ADHD and ASD present distinct problems, these two conditions can also appear to share characteristics [4�C6], making them sometimes problematic to distinguish. For example, inattention and poor social skills are common to both disorders.

However, ADHD and ASD may also share a high rate of comorbidity, with epidemiological studies, for example, estimating 30% prevalence of ADHD amongst ASD patients [7]. In addition to symptoms described in the diagnostic criteria, patients with ASD and/or ADHD tend to also experience a range of other behavioral and developmental problems. Both syndromes are associated with language [8, 9] and motor skill deficits [10, 11] as well as mood disorders [12, 13] and sleep problems [14, 15]. They also tend to involve cognitive deficits including executive functions, time perception, and memory functions [16]. Furthermore, ASD and ADHD are thought to have more extensive developmental problems than other psychiatric conditions with typically later onset (such as mood disorders or anxiety disorders) [17, 18].

Both ASD and ADHD are associated with a range of difficulties, of which only some are located within the diagnostic criteria [19, 20]. However, clinical assessments often focus heavily on the core features of a suspected diagnosis and, as a result, can fail to examine the assortment of problems that an individual presents with. Gillberg has conceptualized the variety of problems characterising some young children in clinical settings as ESSENCE (early symptomatic syndromes eliciting neurodevelopmental clinical examinations) [21]. This approach describes the multifaceted developmental and behavioral symptoms often observed in children with neurodevelopmental syndromes, including ASD and ADHD. ESSENCE presents these problems as belonging to eight areas of functioning: (a) general development, (b) communication and language, (c) social interrelatedness, (d) motor skills, (e) attention, (f) activity, (g) behavior Carfilzomib (conduct), and (h) mood and/or sleep. Gillberg observes that children presenting for clinical examination with one or more of these difficulties are usually treated by only one type of specialist, although specialists from a range of fields would often be more appropriate [21].

As shown in Figure 9, cement-based composites produced with higher quantities (5% to 20%) of metakaolin provide higher strength and resistance to efflorescence, due to a denser microstructure and the controlled concentration of mobile alkalis in the pore solutions, respectively. Figure 9Curves comparing compressive strength versus replacement www.selleckchem.com/products/jq1.html of metakaolin and area of efflorescence versus replacement of metakaolin (NE specimens).3.3. Quantification of Efflorescence Using the Curettage MethodThe results for the quantification of efflorescence using the curettage method are presented in Tables Tables6,6, ,7,7, and and8.8. Clearly, the addition of 15% metakaolin was most effective in inhibiting efflorescence under any exposure environment.

The specimens cured under LTE conditions had a higher quantity of efflorescence than those under NE or CDE. Based on the previous study, higher humidity led to a higher quantity of efflorescence, and efflorescence increased with an increase in the size of moist particles [13]. In addition, efflorescence was proportional to alkali leaching, perhaps due to the larger volume of macropores (particularly those between 200nm and 1000nm) capable of increasing the diffusion coefficient for the migration of Na from geopolymer phase into the solution [14]. Table 6Quantity of efflorescence using the curettage method under NE (unit: g).Table 7Quantity of efflorescence using the curettage method under CDE (unit: g).Table 8Quantity of efflorescence using the curettage method under LTE (unit: g).3.4.

Effect of Metakaolin on Microscopy CharacteristicsThis study employed SEM observations to characterize the microstructural compounds produced with/without replacement metakaolin. Careful analysis of microstructures can reveal the pozzolanic reaction and the gel development. SEM magnification was set at 1,000 and 3,000 times to directly observe the development of cement hydration and pore structure. SEM observation was performed on control specimens after 56 days of aging, shown in Figure 10; large capillary pores, CH, and pore interconnectivity were observed. Figure 10SEM observations for M0 specimens.SEM observation was also applied to specimens with various amounts of replacement metakaolin (5%, 10%, 15%, 20%, and 25%) at 56 days, as shown in Figures Figures11,11, ,12,12, ,13,13, ,14,14, and and15.15.

Clearly, cement-based paste specimens with replacement metakaolin developed a more compact, denser pore structure. Hydration was formed on the surface Entinostat of the M5, M10, M15, and M20 specimens; the microstructure of these samples reduced the mobility of chloride and other ions, resulting in higher compressive strength and a reduction in crack stretching. Figure 11SEM images of M5 specimens.Figure 12SEM images of M10 specimens.Figure 13SEM images of M15 specimens.

AcknowledgmentsThe authors thank the authority of BSMRAU Agricultural University, Gazipur, Bangladesh, http://www.selleckchem.com/products/dorsomorphin-2hcl.html for providing the space for crop cultivation. This research was partly supported by the Universiti Putra Malaysia (UPM), Malaysia.
In recent years, the topic of chaos synchronization has attracted increasing attention in many fields. The result of synchronization of chaotic oscillators is used in nonlinear oscillators [1], circuit experiment [2], secret communication [3], and some other fields. In 1990, the first concept of synchronization was presented by Carroll and Perora [4]. And there are many methods about chaos synchronization such as Lyapunov equation [5], Perora-Carroll (PC) [4] and backstepping control [6].

All of these methods are amid of the synchronization between one master and one slave system do not consist of the synchronization of multimaster systems and multislave systems.Dual synchronization is a special circumstance in synchronization of chaotic oscillators. The first idea of multiplexing chaos using synchronization was investigated in a small map and an electronic circuit model by Tsimring and Sushchik in 1996 in [7]; then the concept of dual synchronization was raised by Liu and Davids in 2000 in [8], which concentrates on using a scalar signal to simultaneously synchronize two different pairs chaotic oscillators, that is, the synchronization between two master systems and two slave systems.Nowadays, there are many dual synchronization methods, such as in 2000 Liu and Davids introduce the dual synchronization of 1-D discrete chaotic systems via specific classes of piecewise-linear maps with conditional linear coupling in [8].

The dual synchronization between the Lorenz and Rossler systems by the Lyapunov stabilization theory is investigated in [9]. The output feedback strategy is used to study the dual synchronization of two different 3-D continuous chaotic systems in [10]. Then the dual synchronization in modulated time-delayed systems is investigated by designing a delay feedback controller in [11]. All of these works are amid of the dual synchronization of integer-order chaotic systems and do not consist of the dual synchronization of fractional-order chaotic systems. In this paper, a new method of dual synchronization of fractional-order chaotic systems is proposed, by a linear controller; the dual synchronization of chaos is obtained. The rest of this paper is organized as follows: in Section 2, we construct a theory frame about the dual synchronization of two different fractional-order Brefeldin_A chaotic systems. By a linear controller, we obtain dual synchronization between two different fractional-order chaotic systems in Section 3.

infausta our results are somewhat CHIR99021 FDA higher than reported in fruits from Malawi [5], Botswana [8], and Tanzania [17]. For L. kirkii, the dry matter content was comparable with the literature data [1]. The average dry matter content of A. digitata kernels was 92.0%, which is in agreement with other results, ranging from 85% to 97% [1, 7, 9, 14, 15, 18�C21]. The average dry matter content of S. birrea kernels was 94.3%, which is at the same level as the results from other reports [1, 11, 15, 22, 23].Table 1Dry matter content, protein, fat, and ash expressed in g/100g dry matter (n = 3). The protein content of the pulp was low in general (below 5%) for all the fruits. This is in agreement with results of other reports, [1, 5, 7, 15�C18]. For A. digitata, however, there is a report showing a much higher protein content, 15.

3% [24]. The protein content in the pulp was significantly lower than in the corresponding kernels (P < 0.05). A. digitata kernels contained on average 39.3% protein and S. birrea kernels 32.6%. For A. digitata, our results are in accordance with other results [7, 18], but there are also reports showing lower protein content, 13�C27% [14, 15, 19, 21], and one report showing higher protein content, 48.3% [20]. The protein content in the kernels of S. birrea was at the same level as found in another report [23]. The high protein content in the kernels is at the same levels as reported for soya beans, around 33% [11], which means that the kernels may be a potential source of protein and can be used to improve the diet in rural communities.

For example, a daily intake of 100g of fresh pulp from the wild fruits studied here would provide around 2�C11% of the recommended daily intake (RDI) for children from 4 to 8 years old, while 20g of A. digitata or S. birrea kernels would provide 32�C39% of the RDI for children of the same age [25]. The protein quality of the kernels seems to be good since high amounts of the essential amino acid lysine as well as of arginine, glutamic acid, and aspartic acid have been reported for A. digitata kernels [15]. S. birrea kernels have been shown to contain high amounts of the essential amino acids phenylalanine, lysine, and threonine [3, 6].The fat content in the pulp was below 2% for all the fruits. The literature data on A. digitata and S. birrea pulp generally show fat contents below 1% [1, 7, 14�C16, 18], while some reports show a higher fat content in A.

digitata, 4% [5, 17, 24]. The pulp of wild fruits is typically low in fat and protein [5], while the kernels are good sources of fat and protein [10]. In the present study, the average fat content was 38.0% in kernels of A. digitata and 60.7% in kernels of S. birrea, and the fat content in the kernels was significantly higher than that in the pulp (P < 0.05). Cilengitide Our data on kernels are in agreement with results from other studies [1, 3, 22, 23], while the fat content was lower in two reports [20, 21] and higher in one [18].

Our first step encompassed creation of ISs for wild type sequence of ASXL1 and 76 sequences with AASs. Second, we calculated ISM scores for each frequency in the IS. In the third step, we performed Mann-Whitney U Test on these scores Pazopanib FGFR related to the frequency with highest amplitude value in IS of wild type sequence��F(0.036). As it did not significantly discriminates between SNPs and mutations, we applied the same statistical test for the next highest peak frequency in the spectrum. We went on with this procedure until we identified IS peak frequency F(0.476) that discriminate disease related mutations (p = 0.018) (Figure 3(a)). 75% of sequences with SNPs had lower and 77% of sequences with mutations had higher values of amplitudes compared to wild type (Figure 4).

Figure 3Process for the selection of significant frequencies from the spectra of ASXL1 (a), EZH2 (b), DNMT3A (c), and TET2 (d).Figure 4Distribution of ISM scores.EZH2 is frequently mutated in lymphoid malignancies, with the hot spot on Tyr641 [45]; however, mutations in myeloid malignancies are spread throughout the entire sequence with no hot spot. ISM algorithm identified frequency F(0.411) that significantly discriminates sequences with SNPs and mutations, with p = 0.003 (Figure 3(b)). Six SNPs containing sequences had amplitude value corresponding to this frequency below the value of wild type, while approximately half of sequences with mutations had higher values of amplitudes than wild type (Figure 4).In DNMT3A sequence, 6 SNPs and 41 mutations were separated at IS frequency F(0.071) with p = 0.

041 (Figure 3(c)). Contrary to the ASXL1 and EZH2,the majority of sequences with SNPs had amplitude values above wild type value (83%), while more than half of the sequences with mutations (51%) had corresponding amplitudes lower than wild type (Figure 4).Finally, we analyzed 45 TET2 sequences with SNPs and 121 with mutations. IS frequency F(0.491) was shown to be significant classifier (p = 0.025) (Figure 3(d)) separating sequences with SNPs (60% below wild type value) and with mutations (55% above wild type value) (Figure 4). Since TET2 variations make the largest proportion of our dataset, we used them for cross-validation of our method for frequency selection. We randomly split them into five groups, and each time we submitted four different groups to the ISM-based algorithm.

All analyses resulted in the identification of F(0.491) as the most important frequency, which indicates minimal bias in our performance evaluation.4.4. Performance of ISM Algorithm on AASs outside CFDs and Comparison with PolyPhen-2 and SIFTThis research is focused on predictions of functional effects of AASs in nCFDs. We compared predictive Dacomitinib power of ISM algorithm and commonly used MSA-based PolyPhen-2 and SIFT on the subset of our data, which contained 108 SNPs and 51 mutations.

Bosscha MD, PhD; E Ritchie MD; M Vermeer, Bosch Medical Centre, Den Bosch; PW de Graaf MD, PhD; B van Etten MD, PhD; C Haazer (I); E Salm MD, PhD (I); selleck screening library Reinier de Graaf Hospital, Delft; B Lamme MD, PhD; EJ Hesselink MD, PhD; H Rommes MD, PhD (I), Gelre Hospitals, Lucas Hospital Apeldoorn; RJ Oostenbroek MD, PhD; L te Velde MD; G Govaert MD; HH Ponssen MD (I), Albert Schweitzer Hospital, Dordrecht; HG Gooszen MD, PhD; MK Dinkelman MD; LPH Leenen MD, PhD (I), University Medical Centre Utrecht; EGJM Pierik MD, PhD; KWW Lansink MD; J Bakker MD, PhD (I), Isala Clinics, Zwolle.

Key staff and steering committee at coordinating center RELAP trial:O van Ruler (investigator), EA Reuland (data management), CW Mahler (investigator), JB Reitsma (epidemiologist), CAJM de Borgie (epidemiologist), KR Boer (quality of life investigator), BC Opmeer (health economist), MA Boermeester (principle investigator, project supervisor, gastrointestinal surgeon) from the Department of Surgery, Academic Medical Center Amsterdam, The Netherlands.The key staff and steering committee received compensation from the grant provided by ZonMw, The Hague, The Netherlands.Financial support:Dutch Organization for Health Research and Development (ZonMw), The Hague, The Netherlands. Health Care Efficiency Program. Grant number: 945-02-028ZonMw approved the study protocol (including design and conduct of the study, data collection and management) after consulting national and international independent reviewers. Final analyses, interpretation of data, manuscript preparation, review and approval of the manuscript were left to the authors’ discretion and were not influenced in any way by ZonMw.

Supported by the Netherlands Organization for Health Research and Development (ZonMW), The Hague, The Netherlands. Grant no. 945-02-028.
Every day you may make progress. Every step may be fruitful. Yet there will stretch out before you an ever-lengthening, ever-ascending, ever-improving path. You know you will never get to the end of the journey. But this, so far from discouraging, only adds to the joy and glory of the climb.Winston ChurchillIntroductionCritical care medicine is a relatively young discipline that has rapidly grown into a full-fledged specialty. Demand for intensive care has steadily escalated, and the ratio of intensive care unit (ICU) to hospital beds is increasing everywhere. ICUs now hold a key position in all hospitals, and critical care physicians Drug_discovery are responsible for managing the ever-increasing numbers of patients with complex, life-threatening medical and surgical disease. Perhaps nowhere else in clinical medicine has the evolution of technology and scientific advance been so apparent and new ideas, concepts, and discoveries moved so fast from bench to bedside.