, 2004 and Van Klinken and Campbell, 2001) These examples show t

, 2004 and Van Klinken and Campbell, 2001). These examples show that the environmental risks related to the introduction of tree species have been underestimated in the past. However, awareness of these risks has grown in recent years, and the invasive potential of tree species is now considered more carefully before any new introductions. The risks of genetic pollution

and hybridization are related to the transfer of tree germplasm to an area where the same or a related species already occurs. Hybridization and introgression are natural evolutionary processes (Arnold, 1992), but the term ‘genetic pollution’ usually refers to a situation where the mixing of gene pools, between different individuals of the same or related species, has been initiated by, or significantly influenced through, human activity. If the seed source used is not local, then planted trees are likely to have a different genetic composition VX-770 solubility dmso from MS-275 in vitro wild

stands, and crossing between them could lead to the dilution and loss of unique diversity in the wild. The subsequent breakdown of co-adapted gene complexes could lead to outbreeding depression (Ledig, 1992). Genetic pollution has been reported for many forest trees. One of them is Juglans hindsii, which is known to have hybridized with many congeners imported for commercial purposes ( Rhymer and Simberloff, 1996). Another well-known example is Populus nigra, which was once widespread but is now extirpated over large parts of Western Europe ( Lefèvre et al., 2001). Its habitats have been considerably reduced by the past transformation of rivers to canals and its gene pool is threatened by the large-scale cultivation of hybrid poplars ( Smulders et al., 2008). Other Abiraterone examples are Platanus racemosa, which is currently disappearing from its native range through introgression

with Platanus × acerifolia ( Rhymer and Simberloff, 1996), and the genetic pollution of native gene pools of eucalypts resulting from plantation establishments in Australia ( Potts et al., 2004). Concerns have also been expressed that cultivated-wild tree hybridisation could result in traits introduced into cultivars through genetic modification (GM) being transferred into natural stands, with potentially significant evolutionary consequences in the wild (see Delplancke et al. (2012) for concerns regarding cultivated Prunus dulcis and wild Prunus orientalis). The environmental risks associated with genetic pollution were largely ignored in the past and it is important not to overstate them now. Strong barriers to hybridisation exist between some related species, such as differences in flowering time or the poor fitness of hybrids, which reduce the risks. One approach to reduce the potentially negative impacts of cultivated-wild tree hybridisation is to deliberately isolate cultivated material or to plant exotic rather than indigenous trees around natural forests and woodlands (Potts et al., 2001).

The unit can process up to four samples independently

The unit can process up to four samples independently Carfilzomib cell line at the same time. The ParaDNA Sample Collector (Life Technologies®: 4484203) is a disposable plastic device used in a similar manner as a traditional cotton swab (Electronic Supplementary Material Fig. 1b). Collection of cellular material

occurs through adsorption onto the plastic head of the device and can be recovered from both evidential swabs (termed indirect sampling) or directly from an evidence item (termed direct sampling). The device is operated by pushing the collar, forcing four sampling tips into a closed position ready for collection (Electronic Supplementary Material Fig. 1c). After sampling, this process is reversed separating the tips before the sample collector is inserted into the 4-well PCR plate, introducing the DNA template while

simultaneously sealing the PCR wells. The ParaDNA Screening Test (Life Technologies®: 4484202) contains four independent PCR [19] reactions pre-loaded into the custom designed 4-well PCR plate (Electronic Supplementary Material Fig. 1d). The assay uses HyBeacon™ technology [9] and [20] to amplify Selleckchem Duvelisib and detect 2 STRs and the Amelogenin gender marker. The TH01 locus (amplified fragment size 143-187 bp, alleles detected 5-9.3 + ), D16S539 locus (amplified fragment size 131-183 bp, alleles detected alleles 8-15 + ) and the gender marker Amelogenin (amplified fragments size 188-194 bp, alleles detected X, Y) are separated into each of the four wells. The ParaDNA Software controls the instrument, analyzes the data and displays the screening result. The software detects changes in fluorescence (ΔRFU) as

a HyBeacon probe melts away from its amplified allele at a specific melting temperature (TM) between 20 °C and 70 °C (Electronic Supplementary Material Fig. 2a). The temperature at which this fluorescence change occurs varies with the length of the amplified allele. This temperature separation enables the software to attribute a proportion of the overall fluorescence change to each possible allele. System variability causes small fluorescence of changes even when an allele has not been amplified. This system noise is determined by considering data from a large number of samples (Electronic Supplementary Material Fig. 2b). Some of these are known to contain the allele of interest and others do not. The noise is then rejected with a simple threshold. The software converts this data into an easily interpretable colour-coded ‘DNA Detection’ result as follows: • Red–No DNA Detected. Fluorescence change consistent with negative control data.

, 1993) The absence of any difference in TI/TTOT between obese p

, 1993). The absence of any difference in TI/TTOT between obese patients and controls can be explained by the progressive adaptation of the respiratory system as weight increases. According to Domingos-Benício et al. (2004), individuals who have been obese for a long

time can adapt to the overload imposed by the adipose tissue. There were no significant differences in VT/TI between the two groups. According to Tobin et al. (1983b), the VT/TI ratio reflects the respiratory drive, and obese individuals do not exhibit alteration in ventilatory drive ( Sampson and Grassino, 1983). Cavallazzi et al. (1981) evaluated the ventilation of obese individuals after the inhalation CDK inhibitor of carbonic gas and observed that despite high variability, all individuals showed an adequate response

to the stimulus. Chlif et al. (2009) evaluated 34 obese patients and did not find differences in the VT/TI from normal values. Weight stabilization usually occurs 1 year after surgery. Selleck Anticancer Compound Library In this study, patients were only followed for 6 months, which may have influenced the results and is a limitation of this study. Another point to be discussed is that sample size calculated after a pilot study with 10 subjects in each group demonstrated the need of more them 1571 subjects. This number is very high and impossible to be attained on this study. Most of the study related to this field had studied about 30 patients. Moreover, even with only 30 subjects on each group it was possible to verify significant differences in most of the variables, showing a positive effect of the weight loss. Significant differences were not found in %RC or %AB. Both groups had high levels of abdominal motion, results that corroborate those observed by Tobin et al. (1983b) in normal individuals and those with other respiratory diseases (Tobin et al.,

1983a). The PhAng, a variable that reflects asynchrony on thoracoabdominal motion, has been studied in healthy and patients (Aliverti et al., 2009, Alves et al., 2008, Oliveira et al., 2009 and Parreira et al., 2010) Our Celecoxib results showed that at preoperative period and at 1 month after surgery, obese patients exhibited higher PhAng values than the control group. Tobin et al. (1987) reported that an increased thoracoabdominal asynchrony is associated with an increase in respiratory load, influencing the elastic withdrawal of the rib cage and lungs (Biring et al., 1999 and Lazarus et al., 1998). The existence of higher asynchrony 1 month after surgery can be attributed to insufficient weight reduction to decrease the overload to the thoracic wall and, also, to postoperative discomfort because patients were still experiencing some pain and discomfort caused by the surgery (Ford et al., 1993). No significant reduction in PhAng was seen at 6 months after surgery compared to preoperative and after 1 month.

, 1996, Kanter and Fordyce, 1993 and Watchko et al , 1988) Findi

, 1996, Kanter and Fordyce, 1993 and Watchko et al., 1988). Findings in these studies raise the possibility

that some central (Gandevia, 2001) or local (Parthasarathy et al., 2007) mechanism may inhibit the respiratory muscles in the face of increased mechanical loads, and thus protect them against fatigue and damage – although at the cost of carbon dioxide (CO2) retention. Experimental evidence supports the existence of local protective mechanisms (Laghi et al., 2003, Mador et al., 1996 and Eastwood et al., 1994). In patients who developed hypercapnia during a failed trial of weaning from mechanical ventilation, we observed sequential recruitment of the extradiaphragmatic muscles (Parthasarathy et al., 2007). The sequence began with greater-than-normal activity of inspiratory muscles followed by expiratory

muscle recruitment. It is known that expiratory muscle activity is not confined to exhalation, but can also occur during inhalation Selleckchem NU7441 and thus limit inspiratory shortening of the diaphragm (Abe et al., 1999). As such, recruitment of extradiaphragmatic muscles may have a dual role during loading: to protect the diaphragm against contractile fatigue, and to improve diaphragmatic neuromechanical coupling by limiting diaphragmatic shortening. Evidence also supports the existence of reflex mechanisms that inhibit central neural output under loaded conditions. Implicated mechanisms include group III and IV afferents and mechanoreceptors originating in the contracting respiratory

muscles (Gandevia, 2001). Reflex inhibition of central neural output causes hypercapnia, a potent source of air hunger (Banzett et al., 1996). This Bortezomib cell line consideration raises the possibility that reflex inhibition of central neural output during loading may also have a dual role: to protect the respiratory muscles against damage and contractile fatigue, and to trigger intolerable air hunger, leading to task failure. The objective of the current study, conducted in healthy volunteers, was to elucidate the physiological mechanisms involved in the development of CO2 retention during progressive inspiratory threshold loading. Methocarbamol In subjects undergoing progressive inspiratory threshold loading, we hypothesized that improvements in diaphragmatic neuromechanical coupling secondary to extradiaphragmatic muscle recruitment are insufficient to prevent alveolar hypoventilation and task failure, and the latter will result primarily from reflex inhibition of central neural output to the diaphragm and air hunger rather than contractile fatigue. Experiments were performed on 18 healthy subjects (4 female), mean (±SE) age 33 ± 2 years; all but one were naïve to the investigation’s purpose. The study was approved by the Institutional Review Board of Edward Hines, Jr. Veterans Affairs Hospital, which conforms to the provisions of the Declaration of Helsinki. Informed consent was obtained in writing from all subjects. Measurements.

Terraces remain along-side incised rivers because flood flows no

Terraces remain along-side incised rivers because flood flows no longer exceed discharge magnitude thresholds for floods to inundate the former floodplains (Leopold et al., 1964). The resulting archetypal incised alluvial river channel

is initially narrow and is characterized by high, steep channel banks with adjacent terraces. Incision in fluvial systems occurs globally and is selleck compound significant with respect to the geomorphic landscape, habitat diversity, and human development (Simon and Darby, 1999). Channel incision may lead to bank erosion and widening (Simon and Hupp, 1986), channel narrowing and embankment (Rinaldi, 2003), increased turbidity (Shields et al., 2010), and reduced habitat heterogeneity (Bravard et al., 1997). Combined with other anthropogenic changes at the landscape scale, incision renders riparian ecology less able to adapt to variable and episodic natural disturbance regimes (Palmer et al., 2008). In this paper, we review the weight of evidence for

natural and human causes of incision. We use the term “Anthropocene” as a metaphor in reference to systems that are affected by intense human interaction. We first note natural factors that may cause channel incision such as climate variation and tectonics, and then review effects of anthropogenic changes in flow to sediment discharge ratios, baselevel, and channelization, taking into account the spatial relationships between forcing factors at the watershed scale and incision. We then present a field study of an Protein Tyrosine Kinase inhibitor incised alluvial

channel (Robinson Creek in Mendocino County, California, USA; Fig. 1) that examined geomorphic evidence and processes for incision, including the timing of the initiation of incision, and short-term variability in channel bed for elevations along the longitudinal profile between 2005 and 2008. We discuss the natural range of process dynamics in stable and incising alluvial systems and examine concepts of feedbacks in coupled human–geomorphic systems as they relate to channel incision—required for effectively managing modern incised systems. Finally, we develop a metric to identify and quantify the extent of incision that may be applied in other alluvial systems. This work has relevance to other incised systems globally where human activities have set in motion a combination of watershed-scale disturbances. Although similar rates and magnitudes of change have occurred in the geologic past within individual watersheds, incision occurring during the “Anthropocene” to an extent such that humans cannot readily manage modern incised rivers requires new conceptual frameworks for understanding such systems. The interplay of multiple factors often makes determining a single cause of incision difficult (Schumm, 1991 and Schumm, 1999).

With only localized and minor overbank flooding, delta plain deve

With only localized and minor overbank flooding, delta plain development on the marine sector was in turn dominated by alongshore marine redistribution of sediment and coastal progradation via successive coastal sand ridge development (Giosan et al., 2005, Giosan et al., 2006a and Giosan et al., 2006b). Human intervention in the Danube delta began in the second half of the 19th century and affected the three major distributaries of

the river in different degrees. Initially, protective jetties were built and successively extended at the Sulina mouth and the corresponding branch was transformed into a shipping channel by shortening and dredging (Fig. 2a; Rosetti and Rey, 1931). After World War II, meander cuts and other engineering works on the other major distributaries also slightly changed the water and, by extension, the sediment partition among them. The main net effect Lumacaftor was that the Chilia branch lost ∼10% of discharge (Bondar and Panin, 2001), primarily to the Sulina channel. Polder construction for agriculture

(Fig. VX-770 solubility dmso 2a) expanded until 1990 to over 950 km2 (over 25% of the ca. 3400 km2 of the delta proper) but restoration of these polders has started and will eventually recover ca. 600 km2 (Staras, 2000 and Schneider, 2010). The most extensive and persistent engineering activity in the delta was the cutting and dredging of shallow, narrow canals. Because the number of secondary channels bringing freshwater to deltaic lakes and brackish lagoons south of the delta was limited and this affected fisheries, Sucrase several canals were dug before 1940s to aid fishing (Fig. 2a; Antipa, 1941). After WWII, the number of canals increased drastically for industrial scale fishing, fish-farming and reed harvesting

(Fig. 2a; e.g., Oosterberg and Bogdan, 2000). Most of these canals were dug to shallow depths (i.e., ca. 1–2 m) and were kept open by periodic dredging. Compared to the pre-WWII period, the length of internal channels and canals doubled from 1743 km to 3496 km (Gastescu et al., 1983). Following a slack phase after the fall of the Communist economy in Romania beginning in 1989, canal dredging is now primarily employed to maintain access for tourist boats into the interior of the delta. The exchange of water between the main distributaries and the delta plain more than tripled from 167 m3/s before 1900 to 620 m3/s between 1980 and 1989 (Bondar, 1994) as a result of canal cutting. The successive relative increases in water transiting the interior of the delta plain correspond to 3.0 and 11.3% respectively for the annual average Danube discharges of 5530 and 5468 m3/s respectively (GRDC, 2010). However, in the same time, the full sediment load entering the delta has drastically diminished from ca. 70 Mt/yr to ca. 25 Mt/yr after the intensive damming of the Danube and its tributaries in the second half of the 20th century (McCarney-Castle et al., 2012 and references therein).

We also

We also Selleck Doxorubicin found that hVISA was generated in vitro by selecting a hetero-MRSA strain ΔIP with imipenem [8] and [21], and that the appearance rate of hVISA

from ΔIP was much higher with imipenem than with vancomycin as a selective agent (2.0 × 10−5 vs. 3.6 × 10−7) [21]. Other regulator mutations are found in the walKR TCRS, where walK (yycG/vicK) is a sensor histidine kinase and walR (yycF/vicR) is the cognate response regulator. The TCRS is supposed to be the regulator of cell wall metabolism, including expression of autolysins [28], [29], [30] and [31]. Introduction of a walK mutation into VSSA strain N315LR5 raised vancomycin resistance from 1 mg/L to 3 mg/L and significantly depressed Triton X-100-induced autolysis [29]. As many as 18 (54.5%) of 33 tested VISA strains possessed mutations in the walK gene ( Table 1). Mutation in the response regulator gene graR(N197S) is present check details in Mu50 [32]. In another clinical MRSA strain, a mutation in the sensor kinase gene graS(T136I) was demonstrated to confer an hVISA phenotype on a VSSA strain [33].

In the Mu50 chromosome, graR(N197S) is one of the nine non-synonymous mutations compared with the Mu3 chromosome [32]. Introduction of graR(N197S) on a multiple-copy plasmid converted Mu3 into VISA with an MIC of 4 mg/L. However, introduction of graR(N197S) into Mu3 as a single copy by gene replacement raised the vancomycin MIC slightly from 2 mg/L to 3 mg/L, i.e. to the degree of resistance of hVISA. Conversion to VISA was finally achieved by subsequent introduction of an rpoB mutation. The rpoB gene encodes the β subunit of RNA polymerase (see below). Roflumilast Introduction of the graR mutation enhanced gene expression of the ABC transporter genes vraDE-SAS091, vraFG and mprF [32] and [34]. mprF encodes phosphatidylglycerol lysyltransferase that modifies membrane phosphatidylglycerol

with l-lysine [35]. The graRS genes together with vraFG and the adjacent orf graX are proposed to constitute the five-component system graXRS–vraFG to sense cationic antimicrobial peptides [36]. Although rarely represented in clinical VISA strains, graRS mutation is another regulator mutation that could convert VSSA into hVISA [33]. The most prevalent mutations in VISA clinical strains were those in the rpoB gene, which were carried by 21 (63.6%) VISA strains ( Table 1). Although rpoB is not a regulator gene, its mutation drastically changes the transcription profile of the cell much more than any of the regulator mutations [37]. We therefore regarded rpoB mutation as a ‘regulatory mutation’ [34] and [38]. As many as 29 (87.9%) of the 33 tested VISA strains possessed mutations in either one of the three genetic loci rpoB, walRK and vraUTSR ( Table 1).

Breastfeeding was defined as a form of feeding where the child is

Breastfeeding was defined as a form of feeding where the child is fed human milk (directly from the breast or expressed) regardless of other foods; in bottle-feeding, the child ingests any kind of liquid or semisolid food from a bottle. In the absence of a single clinical PLX4032 protocol for the diagnosis of mouth breathing, two methods were used. The first was a written history, as

established by Abreu et al.,13 which advocates the following clinical manifestations as major signs: snoring, mouth open while sleeping, drool on the pillow, stuffy nose every day. The following are considered as minor signs: itchy nose; occasional congested nose; difficulty breathing at night or restless sleep; irritability or drowsiness during the day; difficulty or delayed food swallowing; episodes of throat infection, ear infection or sinusitis; and difficulty in school or grade repetition. The occurrence of two major signs or two minor signs in the patient’s history is compatible with mouth breathing. The second method used was established by observation and palpation of the mentalis

muscle. The relationship of the upper and lower lips to the resting position of the tongue was evaluated, and breath analysis of the child was performed while he/she was in a more relaxed position, according to the method established by Moyers.18 The test was indicative of mouth breathing if the child showed a lack of lip seal. With these two diagnostic methods, the child’s breathing pattern type was determined; children who presented characteristics compatible with mouth breathing in both methods were considered as AZD2281 mouse mouth breathers. A pre-test questionnaire was administered to 20 mothers who did not participate in the study, in an attempt to make the necessary adjustments for a better MycoClean Mycoplasma Removal Kit understanding of the addressed factors. The legal guardians signed the consent form, according to the recommendations of Resolution 196/96

of the Ministry of Health and the Declaration of Helsinki. The study was approved by the Ethics in Research Committee of UFPI (Opinion No. CAAE 0039.0.045.000-10). The data were processed and analyzed using Stata, version 11.0 (Stata Corporation – College Station, TX, USA). To assess the association between variables, the chi-squared test was used. The multivariate analysis included variables with p < 0.20 in the bivariate analysis, using Poisson regression in order to verify the independent variables associated with the presence of oral breathing, controlled for possible confusion factors (adjusted prevalence ratios [PR]). The results were presented as PRs, and the 95% confidence interval and associations were verified by the Wald’s test. The results with p < 0.05 were considered statistically significant. The study population was composed of 139 male children (55.2%) and 113 female children (44.

2), which both revealed significant increase of the inflammatory

2), which both revealed significant increase of the inflammatory infiltrates, with expansion of the bronchopneumonia in both the Epigenetics inhibitor middle and lower right lobes, as well as accumulation of small amount of pleuritic fluid. Antibiotic treatment changed from amoxicillin-clavulanic acid to piperacillin-tazobactam, in order to cover possible hospital-acquired pathogens, but the patient remained feblile. Simultaneously, the patient reported new onset, worsening cough, and, particularly, bouts of cough when swallowing liquids. This new symptom raised clinical suspicion of a communication between the respiratory tree and the upper gastrointestinal tract. The patient was advised to stop eating, and was subjected to a barium-oesophagography,

which confirmed the presence of a BOF (Fig. 3). The patient was referred to a specialized department of Cardio-Thoracic Surgery, where open right thoracotomy and resection of the fistulous tract, along with right middle lobectomy, were performed. The fistula was about 3 cm long, connecting the

right middle segmental bronchus and the lower third of the oesophagus, while the right middle lobe macroscopically resembled liver parenchyma. The histopathological examination reported that the whole lobe removed was atelectatic with evidence of chronic pneumonitis, while medium-sized bronchi were moderately dilated and full of cellular debris. The fistula was covered with squamous epithelial tissue. No evidence of malignancy or granuloma formation was found in the samples taken from the reactively hyperplastic hilar lymph nodes. Post-operative course of the patient

2-hydroxyphytanoyl-CoA lyase was excellent and the patient was discharged 8 days later. Congenital communications ABT-888 research buy between the respiratory tree and the oesophagus are rare developmental anomalies (1:3000 to 1:4500 live births) resulting from failure of the lung bud to separate completely from the foregut, a procedure that takes place between the 4th and the 6th weeks of gestation.4 In the majority of cases, this malformation is accompanied by oesophageal atresia, and is typically presented in infancy.1, 2, 3 and 4 However, in the so-called “H-type” fistula, which comprises only 3–6% of all cases, the oesophagus is otherwise normal, communicating with either the trachea or a bronchus, formulating either a TOF or a BOF, respectively.1 and 2 Congenital BOFs were first described by Negus in 19292 and 5 and were classified into four categories by Braimbridge and Keith in 1965.3 So far, only about 100 cases have been reported in the literature.1 Their presentation may be delayed until childhood or adult life, with a median age of 33 years old, while the duration of symptoms can vary from 6 months to 50 years, with a mean of 17 years.1 and 2 No sex predominance has been described.1 and 2 The majority (90%) of fistulas are type II according to Braimbridge classification.5 The communication is usually short and is running directly from the oesophagus to a main or segmental bronchus.

Plasma was harvested immediately by 10 min of centrifugation at 4

Plasma was harvested immediately by 10 min of centrifugation at 4 °C, 2765g (Multifuge 1 S−R, Heraeus, Hanau, Germany) and stored at −80 °C until analysed. At the end of the experiment, the animals were sacrificed. EDTA plasma samples were processed by protein precipitation of 50 µL plasma with 200 µL ice-cold 0.4% citric acid in acetonitrile containing

15 ng/mL aripiprazole-d8. The samples were mixed for 10 min in a shaking apparatus followed by centrifugation at 5000g for 10 min at 15 °C and 150 µL supernatant was transferred to a 2 mL deep well plate. Calibration standards and quality control (QCs) were prepared by adding standard PCI-32765 supplier solution to blank plasma and prepared similarly to the plasma samples. The analysis was performed by HPLC–MS/MS using a Waters Acquity-Xevo TQ system controlled by UNIFI. The separation was done on a Waters Spherisorb Silica column (3 µm, 100 × 2.1 mm2) with a mobile phase consisting of water/acetonitrile (25/75 v/v) containing 1% formic acid, at a flow rate of 0.8 mL/min and a column oven temperature of 45 °C. A 3 µL sample was injected in partial loop with needle overfill mode. The mass spectrometer was operated

in the positive electrospray mode with a desolvation temperature of 650 °C. The analytes Akt inhibitor were detected by multiple-reaction-monitoring: aripiprazole lauroxil (660.39–460.16 m/z), N-hydroxymethyl aripiprazole (478.17–448.16 m/z) and aripiprazole (476.15–285.09 m/z). The run time of the assay was 3.5 min with the peaks eluting between 1.45 and 1.84 min. The assay showed linearity over the concentration range of 2.00–1000 ng/mL. Liothyronine Sodium Results obtained are presented as means and the standard error of the mean (mean ± SEM) unless otherwise stated. Pharmacokinetic parameters were calculated by using Phoenix version 6.3.0.0395 (Pharsight Corporation, Mountain View, CA, USA). The plasma concentration–time profiles of the three compounds after intravenous dosing were fitted to a two-compartment model. The area under the curve (AUC) was determined using the linear trapezoidal method and

extrapolation of the last measured plasma concentration to infinity. It is possible to prepare stable N-acyloxyalkyl derivatives of, e.g., tertiary or some N-heterocyclic amines and secondary amides, which are susceptible to enzymatic hydrolysis by esterases, with subsequent spontaneous decomposition, as demonstrated with pilocarpine [ 37], theophylline [ 38], penicillin G [ 39] and various carboxylic acid agents [ 40]. For aripiprazole a similar stable derivatisation can be made at the lactam moiety, where the conversion and the relative presence of the three components – prodrug, intermediate and aripiprazole – in the bioconversion was investigated in vitro and in vivo in the present work. To investigate the rate of biological conversion, two experiments were conducted using either N-hydroxymethyl aripiprazole added into a phosphate buffer or aripiprazole lauroxil added to rat plasma at 37 °C.