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81.
Aim: The aim of this study was to assess the relationship between supine high blood pressure and orthostatic hypotension both in Type 1 (T1DM) and Type 2 (T2DM) diabetic patients. Patients and Methods: Our study included 321 T2DM patients (153 M/168 F; mean age 62.3 (14.2 yr; duration of disease 12.1 (7.6 yr) and 116 T1DM patients (65 M/51 F; mean age 39.7 (9.2 yr; duration of diabetes 11.9 (8.1 yr). Patients with orthostatic hypotension were divided into 3 groups: A – without symptoms; B – mild/moderate symptoms (short and tolerable dizziness when standing); C – severe symptoms (persistent and disabling dizziness or even fainting in upright position). Results: Arterial hypertension was registered in 67.6% of T2DM patients (217 from 321 cases) and in 50.0% of T1DM patients (58 from 116 cases). Orthostatic hypotension (defined as a decrease in systolic blood pressure (30 mm Hg)) was encountered in 64.5% in T2DM patients (207 out of 321 cases) and in 60.3% of T1DM patients (70 out of 116 cases). From 207 T2DM patients with orthostatic hypotension, 105 were in Group A (50.7%), 89 in Group B (42.99%) and 13 in Group C (6.28%), while from 70 T1DM patients with orthostatic hypotension 14 were in Group A (20.0%), 51 in Group B (72.8%) and 5 in Group C (7.14%). An association of supine arterial hypertension with orthostatic hypotension was registered in 96 (29.9%) T2DM patients (68 of them receiving antihypertensive treatment) and in 25 (21.5%) T1DM patients (19 of which were on antihypertensive treatment). From the 18 patients with severe orthostatic hypotension (13 T2DM and 5 T1DM), supine arterial hypertension was registered in 5 cases (3 T2DM and 2 T1DM). In 4 of these 5 cases, patients were receiving antihypertensive treatment. Discontinuation of this treatment led to a decrease in the intensity of clinical signs of orthostatic hypotension in 4 out of 5 cases. An improvement of clinical symptoms of orthostatic hypotension was recorded in about 1/3 of hypertensive patients after discontinuation or just lowering of the dose of antihypertensive drugs (26 out of 87 cases). Conclusion: An association between hypertension and orthostatic hypotension is frequent both in T1DM and in T2DM, rising in difficulties for treatment. The treatment of hypertension in diabetic patients should take into account the possible orthostatic hypotension induced by some of the antihypertensive drugs.  相似文献   
82.
Since the first medical student ultrasound electives became available more than a decade ago, ultrasound in undergraduate medical education has gained increasing popularity. More than a dozen medical schools have fully integrated ultrasound education in their curricula, with several dozen more institutions planning to follow suit. Starting in June 2012, a working group of emergency ultrasound faculty at the California medical schools began to meet to discuss barriers as well as innovative approaches to implementing ultrasound education in undergraduate medical education. It became clear that an ongoing collaborative could be formed to discuss barriers, exchange ideas, and lend support for this initiative. The group, termed Ultrasound in Medical Education, California (UMeCali), was formed with 2 main goals: to exchange ideas and resources in facilitating ultrasound education and to develop a white paper to discuss our experiences. Five common themes integral to successful ultrasound education in undergraduate medical education are discussed in this article: (1) initiating an ultrasound education program; (2) the role of medical student involvement; (3) integration of ultrasound in the preclinical years; (4) developing longitudinal ultrasound education; and (5) addressing competency.  相似文献   
83.
Parkinson's disease (PD) consists of a neurodegenerative pathology that has received a considerable amount of attention because of its clinical manifestations. The most common treatment consists of administering the drugs levodopa and biperiden, which reduce the effectiveness of the disease and the progress of its symptoms. However, phytotherapy treatment of PD has shown great potential in retarding the loss of dopaminergic neurons and minimizing the behavioral abnormalities. The aim of this study is to systematically review the use of supplemental herbal plants with cellular protective effect and behavioral activity in in vivo and in vitro experimental models. A total of 20 studies were summarized, where the effectiveness of herbal extracts and their isolated bioactive compounds was observed in animal models for PD. The main neurochemical mechanisms found in these studies are schematically represented. The herbal extracts and their biocompounds have antioxidant, anti‐apoptotic, and antiinflammatory properties, which contribute to avoiding neuronal loss. Reports show that besides acting on the biosynthesis of dopamine and its metabolites, these compounds prevent D2 receptors' hypersensitivity. It is suggested that further studies need be conducted to better understand the mechanisms of action of the bioactive compounds distributed in these plants. Copyright © 2017 John Wiley & Sons, Ltd.  相似文献   
84.
Behavioral effects of psychollatine, a new glycoside indole monoterpene alkaloid isolated from Psychotria umbellata, was investigated in models of anxiety, depression, memory, tremor, and sedation related to 5-HT and/or GABA neurotransmission. The GABA antagonist picrotoxin and the 5-HT2 antagonist ritanserin were used to examine the role of GABA and 5-HT2 receptors in psychollatine-induced effects. In the light/dark and hole-board models of anxiety, diazepam (0.75 mg/kg) and psychollatine (7.5 and 15 mg/kg) showed anxiolytic-like effect at doses that do not increase sleeping time nor alter spontaneous locomotor activity. The anxiolytic effect of psychollatine was prevented by prior administration of ritanserin, but not of picrotoxin, indicating that 5-HT2 but not GABA receptors are implicated. In the forced swimming model of depression, psychollatine (3 and 7.5 mg/kg) effects were comparable to the antidepressants imipramine (15 mg/kg) and fluoxetine (20 mg/kg). Psychollatine suppressed oxotremorine-induced tremors in all doses. In the step-down learning paradigm, diazepam (0.85 mg/kg), MK-801 (0.15 mg/kg), and psychollatine 100 mg/kg impaired the acquisition of learning and memory consolidation, without interfering with retrieval. It is concluded that the effects of psychollatine at the central nervous system involve serotonergic 5HT2(A/C) receptors.  相似文献   
85.
Eighteen carbapenem-resistant, OXA-48-positive enterobacterial isolates recovered from Turkey, Lebanon, Egypt, France, and Belgium were analyzed. In most isolates, similar 70-kb plasmids carrying the carbapenemase gene blaOXA-48 were identified. That gene was located within either transposon Tn1999 or transposon Tn1999.2, which was always inserted within the same gene. This work highlights the current plasmid-mediated dissemination of the OXA-48 carbapenemase worldwide.Carbapenem-hydrolyzing β-lactamases belonging to Ambler classes A, B, and D have been reported worldwide among Enterobacteriaceae (22). The extensive spread of Ambler class A carbapenemases of the KPC type highlights that carbapenemases may rapidly become threatening (17). Acquired class D ß-lactamases possessing carbapenemase properties have been reported previously, being identified mainly in Acinetobacter sp. (18, 21) and occasionally in Enterobacteriaceae. The chromosome-encoded oxacillinase OXA-23 was previously described for Proteus mirabilis (4), and the oxacillinase OXA-48 was first identified in a Klebsiella pneumoniae isolate from Turkey (20). Since then, several other OXA-48-producing isolates of various enterobacterial species (Citrobacter freundii and Escherichia coli) have been reported, mainly from Turkey (1, 6, 11, 16) but also from Belgium (8), from Lebanon (15), and more recently from the United Kingdom (14, 23a), India (3a), and Argentina (6a). So far, the blaOXA-48 gene has been found to be plasmid borne and located between two identical insertion sequences, IS1999, forming the composite transposon Tn1999 (3). We have analyzed here the genetic backgrounds associated with the blaOXA-48 gene among Enterobacteriaceae isolates collected from different countries.The study included 18 OXA-48-positive clinical isolates of K. pneumoniae (13 isolates), Enterobacter cloacae (2 isolates), Providencia rettgeri (1 isolate), C. freundii (1 isolate), and E. coli (1 isolate). Isolates were mainly from the Turkish cities Istanbul, Ankara, and Izmir (n = 14) (Table (Table1).1). Among the 13 K. pneumoniae isolates, at least Kp11978 (20) and KpB had been sources of nosocomial outbreaks (6). A single K. pneumoniae isolate (KpBEL) was recovered from Brussels, Belgium (8); another K. pneumoniae isolate (KpL) from Beirut, Lebanon (15); another K. pneumoniae isolate from the Bicêtre Hospital (KpBIC), Paris, France (this study); and another K. pneumoniae isolate from Gizah, Egypt (KpE) (8a). Samples were isolated from blood (KpI1, KpI2, KpB, and Enc1), urine (PR, KpBEL, KpL, Kp11978, and KpBIC), cerebrospinal fluid (Enc2), and catheter (KpE). Isolates from Belgium, France, Egypt, and Lebanon were from patients who did not report recent travel history.

TABLE 1.

MICs of β-lactams for the 18 isolates of Enterobacteriaceae and their transconjugants and/or transformants (pOXA-48) E. coli J53 and E. coli TOP10
β-Lactam(s)aMIC (μg/ml) of β-lactam forb:
MIC (μg/ml) of β-lactam forb:
Kp11978 (Istanbul; OXA-48, SHV-2a, TEM-1)E. coli J53(pA-1)KpB (Istanbul; OXA-48, CTX-M-15)E. coli J53(pBb)Kp3A (Ankara; OXA-48)E. coli J53(p3A)Kp4A (Ankara; OXA-48, CTX- M-15), Kp5A (Ankara; OXA-48, SHV-5), Kp6A (Ankara; OXA-48, TEM-150)E. coli J53(p4A, p5A, p6A)Kp7A (Ankara; OXA-48)E. coli J53(p7A)KpI-1 and KpI-2 (Izmir; OXA- 48, CTX-M-15)E. coli J53(pI-1, pI-2)KpBIC (Paris; OXA-48)E. coli TOP10(pBIC)KpE (Gizah; OXA-48, CTX-M-15)E. coli J53(pE)KpBEL (Brussels; OXA-48)E. coli J53(pBEL)KpL (Beirut; OXA-48)E. coli J53(pL)PR (Izmir; OXA-48, TEM-101)E. coli TOP10(pPR)Enc1 (Istanbul; OXA-48, SHV-5)E. coli J53(pEnc1)Enc2 (Istanbul; OXA-48, SHV-2a)E. coli J53(pEnc2)CF (Istanbul; OXA-48, VEB-1)E. coli J53(pCF)EcA (Ankara; OXA-48, TEM-150)E. coli J53(pEcA)E. coli J53E. coli TOP10
Imipenem642160.5>320.75>320.38>320.75240.50.50.5220.750.75>164>321.50.50.50.750.75>320.75240.750.060.06
Ertapenem640.19>320.25>320.25>320.12>320.19240.2520.53342>164>320.750.50.1250.750.19>320.25>320.250.060.06
Meropenem640.25320.12>320.12>320.094>320.12160.0940.50.5220.50.5>160,19>320.250.50.0940.750.12>320.12240.190.060.06
Amoxicillin>512>512>512>512>512>512>512>512>512>512>512>512>512>512>512>512>256>256>256>256>256>256>512>512>512>512>512>512>256>25644
Amoxicillin + clav. acid>512128>512>512>512>512>512>512>512>512>512>512>512>512>512>512>256>256>256>256>256>256>512>512>512>512>512>512>256>25644
Ticarcillin>512>512>512>512>512>512>512>512>512>512>512>512>512>512>512>512>256>256>256>256>256>256>512>512>512>512>512>512>256>25624
Ticarcillin + clav. acid>512128>512>512>512>512>512>512>512>512>512>512>512>512>512>512>256>256>256>256>256>256>512>512>512>512>512>512>256>25624
Piperacillin>5128>512>512>512512>512>512>512>512>512512>512>512>512512>2561289664>256128>512>512>512>512>512>512>25612812
Piperacillin + tazobactam5124>512>512>512512>512>512>512>512>512512>512>512>512512>2561289664>256128>512>512>512>512>512>512>25612812
Cephalotin>5120.5>51216>51216>51216>51216>51216>51216>512161616328>51216>51216>51216>512>512>5121644
Cefotaxime640.06>5120.510.5640.120.50.5640.120.50.5640.120.120.121.50.256432>5120.255120.25640.12640.120.060.06
Ceftazidime5120.12>51210.250.255120.120.120.125120.120.120.125120.1210.750.750.75512512>5120.75320.755120.755120.750.060.06
Cefepime320.06>512<0.50.50.12320.120.50.5320.120.50.5320.120.120.120.120.06320.540.12320.12320.12320.120.030.06
Aztreonam5120.06>512<0.120.060.065120.060.060.065120.060.060.065120.060.060.060.060.065120.06>5120.065120.065120.065120.060.030.06
Cefoxitin12821284221282128212821282128222821284>512251221282128224
Open in a separate windowaclav. acid, clavulanic acid.bKp, K. pneumoniae; Enc, E. cloacae; CF, C. freundii; PR, P. rettgeri; Ec, E. coli.Antibiotic susceptibility of the isolates was determined by the disk diffusion method (7). MICs of β-lactams were determined using Etest strips (AB bioMérieux, Solna, Sweden). All isolates were resistant to penicillins. Fourteen of the 18 isolates were resistant to carbapenems according to the CLSI guidelines (Table (Table1)1) (7). The four remaining isolates (KpBIC, KpE, Enc1, and Enc2) exhibited MICs of carbapenems remaining in the intermediate or in the susceptible range. Resistance to broad-spectrum cephalosporins was observed for most of the isolates. However, isolates Kp3A, Kp7A, KpBEL, KpL, and KpBIC remained susceptible to broad-spectrum cephalosporins (Table (Table1).1). All isolates were resistant to fluoroquinolones, except isolates Kp6A, Enc1, and Enc2. All isolates were resistant to aminoglycosides and sulfamethoxazole, except isolate CF, which remained susceptible to the latter antibiotic.Carbapenemase- and extended-spectrum-β-lactamase (ESBL)-encoding genes were identified by PCR experiments using previously designed primers (6, 8), followed by sequencing. Additional ESBL production was detected by synergy tests as described previously (12). Positive results for ESBL production were observed for isolates EcA, Enc1, Enc2, Kp4A, Kp5A, Kp6A, KpI-1, KpI-2, and KpE. Several ESBL determinants were identified, including CTX-M-15, SHV-5, SHV-2a, TEM-101, TEM-150, and VEB-1 (Table (Table11).Isolates belonging to the same species (13 K. pneumoniae isolates or two E. cloacae isolates) were compared by pulsed-field gel electrophoresis (PFGE) as described previously (6). Ten pulsotypes were identified among the 13 K. pneumoniae isolates. The two K. pneumoniae isolates from Izmir were clonally related, and the three K. pneumoniae isolates from Ankara (Kp4A, Kp5A, and Kp6A) shared very similar PFGE patterns. The two E. cloacae isolates recovered from Istanbul were not clonally related (Fig. (Fig.11).Open in a separate windowFIG. 1.Pulsed-field gel electrophoresis patterns of the 13 OXA-48-producing K. pneumoniae isolates and the two OXA-48-producing E. cloacae isolates. (A) Lane 1, Kp3A; lane 2, Kp4A; lane 3, Kp5A; lane 4, Kp6A; lane 5, Kp7A; lane 6, KpI-1; lane 7, KpI-2; lane 8, unrelated K. pneumoniae isolate (included as a comparative strain); lane 9, Enc1; lane 10, Enc2; lane 11, unrelated E. cloacae isolate (included as a comparative strain); lane M, molecular size marker. (B) Lane 1, Kp3A; lane 2, Kp11978; lane 3, Kp4A; lane 4, Kp7A; lane 5, KpI-1; lane 6, KpL; lane 7, KpB; lane 8, KpBEL; lane 9, KpE; lane 10, KpBIC; lane M, molecular size marker.Transferability of the blaOXA-48 gene was studied by conjugation experiments as described previously (6). When conjugation experiments failed, plasmid DNA extract was used for transformation as described previously (20). Transformants were selected on LB agar containing ticarcillin (50 μg/ml). Transconjugants and transformants with decreased susceptibility to carbapenems were obtained for all isolates (Table (Table1),1), and MICs for the transconjugants/transformants remained in the susceptible range. The E. coli transformant obtained from the P. rettgeri isolate exhibited reduced susceptibility to carbapenems associated with resistance to cefotaxime and ceftazidime.Plasmids were analyzed by using the Kieser technique (13). A 70-kb plasmid was identified in all transconjugants/transformants (data not shown). However, a 150-kb plasmid was identified in the blaOXA-48-positive transformant obtained with the PR isolate. The blaOXA-48 and blaTEM-101 genes were codetected on the same 150-kb plasmid, as confirmed by Southern blot hybridization as described previously (20) (data not shown), explaining the resistance to all β-lactams of the PR isolate and its transformant (Table (Table1).1). Plasmid restriction profiles were compared as described previously (10) (data not shown), and very similar restriction patterns (suggesting highly related structures) were obtained for all of the 70-kb plasmids but not for the 150-kb plasmid pPR.PCR mapping was used to assess the presence of insertion sequence IS1999 upstream of the blaOXA-48 gene, to confirm the presence of transposon Tn1999, and to identify the transposon insertion site for all of the OXA-48-positive isolates (3, 20). In all isolates, the blaOXA-48 gene was flanked by two copies of IS1999, as described previously (3). The prototype IS1999 located at the left extremity of transposon Tn1999 was identified in isolates Kp3A, Kp4A, Kp5A, Kp6A, Kp7A, CF, PR, Enc1, and Enc2. Insertion of IS1R into IS1999 as described for KpB (6) and giving rise to Tn1999.2 was identified for isolates EcA, KpBIC, KpI, KpL, KpBEL, and KpE (Fig. (Fig.2).2). In isolate Kp11978, transposon Tn1999 had been identified to be inserted into the tir gene, being functionally homologous to the F3 gene encoding the factor F involved in the plasmid replicative machinery (23). By use of a primer located upstream of Tn1999 inserted into the tir gene, insertion of Tn1999 at the same target site was evidenced in all of the blaOXA-48-positive plasmids except for the pPR plasmid (Fig. (Fig.2).2). Inverse PCR performed as described previously (3) was used for identifying the blaOXA-48-surrounding structures in isolate PR. Sequencing of the obtained amplicons indicated that Tn1999 had targeted a gene encoding a phosphoadenosine phosphosulfate reductase (ΔPPR).Open in a separate windowFIG. 2.Genetic environments of the blaOXA-48-carrying plasmids identified among the 18 OXA-48-positive Enterobacteriaceae isolates. (A) Structure described for pA-1, p3A, p4A, p5A, p6A, p7A, pCF, pEnc1, and pEnc2. (B) Structure of the 150-kb pPR plasmid. (C) Structure described for pBb, pI, pL, pBEL, pEcA, pBIC, and pE.Attempts to identify the incompatibility group of the 70-kb OXA-48-positive plasmids failed using a PCR-based replicon typing method as described previously (5). Since rep genes are often located close to the hot spots for resistance gene integration, cloning experiments were performed to study these plasmids further. A gene encoding phage replication protein P (RepP) was identified upstream of the blaOXA-48 gene. Primers specific for the repP gene were designed (RepPA, 5′-AATGGTTAACTTTGACTGTG-3′; RepPB, 5′-GCACGATTTAGAGGTCTAC-3′), and positive results were obtained for all 70-kb plasmids. Association of the repP gene with the blaOXA-48 gene on the 70-kb plasmid was confirmed by hybridization with a specific RepP probe (data not shown). However, the repP gene could not be detected on the 150-kb plasmid identified from isolate PR. Our study showed the spread of a blaOXA-48-carrying plasmid among different enterobacterial species, being identified first in Turkey and later in other European countries and in the Middle East. The present work indicates that dissemination of the blaOXA-48 gene is not driven by the dissemination of a single K. pneumoniae clone. Since the blaOXA-48-carrying plasmid confers by itself a low level of resistance to carbapenems, clinical laboratory detection of OXA-48-producing strains may be difficult. Since the reservoir of blaOXA-48 has been identified in the waterborne Gram-negative organism Shewanella oneidensis (19), it is likely that the process leading to the dissemination of this gene may be the consequence of a wide interspecies exchange. In addition, since plasmids belonging to the RepP group have been described among Pseudomonas sp., phytopathogenic Xanthomonas sp., and samples from soils and sludges (2, 9, 24), it may be hypothesized that the blaOXA-48 gene could also be identified in those species. This work underlines that besides class B (VIM and IMP) and class A (KPC) carbapenemases, the class D carbapenemase OXA-48 type might contribute significantly to carbapenem resistance in Enterobacteriaceae.  相似文献   
86.
PurposeBiallelic loss-of-function variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD) responsible for Amish infantile epilepsy syndrome. All Amish patients carry the homozygous p.(Arg288Ter) variant arising from a founder effect. To date only 10 patients from 4 non-Amish families have been reported. Thus, the phenotypical spectrum of GM3SD due to other variants and other genetic backgrounds is still poorly known.MethodsWe collected clinical and molecular data from 16 non-Amish patients with pathogenic ST3GAL5 variants resulting in GM3SD.ResultsWe identified 12 families originating from Reunion Island, Ivory Coast, Italy, and Algeria and carrying 6 ST3GAL5 variants, 5 of which were novel. Genealogical investigations and/or haplotype analyses showed that 3 of these variants were founder alleles. Glycosphingolipids quantification in patients’ plasma confirmed the pathogenicity of 4 novel variants. All patients (N = 16), aged 2 to 12 years, had severe to profound intellectual disability, 14 of 16 had a hyperkinetic movement disorder, 11 of 16 had epilepsy and 9 of 16 had microcephaly. Other main features were progressive skin pigmentation anomalies, optic atrophy or pale papillae, and hearing loss.ConclusionThe phenotype of non-Amish patients with GM3SD is similar to the Amish infantile epilepsy syndrome, which suggests that GM3SD is associated with a narrow and severe clinical spectrum.  相似文献   
87.
88.
AIM: To identify the associated risk factors for hyperechogenic pancreas (HP) which may be observed on endoscopic ultrasound (EUS) and to assess the relationship between HP and obesity. METHODS: From January 2007 to December 2007, we prospectively enrolled 524 consecutive adults who were scheduled to undergo EUS. Patients with a history of pancreatic disease or with hepatobiliary or advanced gastrointestinal cancer were excluded. Finally,284 patients were included in the analyses. We further analyzed the ri...  相似文献   
89.
The essential oils obtained from the aerial parts of five species of Cunila (Lamiaceae) native to Southern Brazil were analyzed by GC and GC/MS. The oil of Cunila angustifolia was characterized by sabinene; Cunila incana is rich in α-pinene and β-pinene, Cunila spicata and Cunila microcephala presented menthofuran as the main component, and in the essential oil of Cunila incisa, the major component was 1,8-cineole. Laboratory tests were carried out to determine the effect of the essential oils of the above cited plants on larvae of the cattle tick Riphicephalus (Boophilus) microplus. C. angustifolia, C. incana, and C. spicata were the most active samples killing almost the totality of the larvae. C. incisa and C. microcephala showed low acaricidal effect.  相似文献   
90.
BACKGROUND AND PURPOSE: In the framework of an ESTRO ESQUIRE project, the BRAPHYQS Physics Network and the EQUAL-ESTRO laboratory have developed a procedure for checking the absorbed dose to water in the vicinity of HDR or PDR sources using a mailed TLD system. The methodology and the materials used in the procedure are based on the existing EQUAL-ESTRO external radiotherapy dose checks. MATERIALS AND METHODS: A phantom for TLD postal dose assurance service, adapted to accept catheters from different HDR afterloaders, has been developed. The phantom consists of three PMMA tubes supporting catheters placed at 120 degrees around a central TLD holder. A study on the use of LiF powder type DTL 937 (Philitech) has been performed in order to establish the TLD calibration in dose-to-water at a given distance from (192)Ir source, as well as to determine all correction factors to convert the TLD reading into absorbed dose to water. The dosimetric audit is based on the comparison between the dose to water measured with the TL dosimeter and the dose calculated by the clinical TPS. Results of the audits are classified in four different levels depending on the ratio of the measured dose to the stated dose. The total uncertainty budget in the measurement of the absorbed dose to water using TLD near an (192)Ir HDR source, including TLD reading, correction factors and TLD calibration coefficient, is determined as 3.27% (1s). RESULTS: To validate the procedures, the external audit was first tested among the members of the BRAPHYQS Network. Since November 2004, the test has been made available for use by all European brachytherapy centres. To date, 11 centres have participated in the checks and the results obtained are very encouraging. Nevertheless, one error detected has shown the usefulness of this audit. CONCLUSION: A method of absorbed dose to water determination in the vicinity of an (192)Ir brachytherapy source was developed for the purpose of a mailed TL dosimetry system. The accuracy of the procedure was determined. This method allows a check of the whole dosimetry chain for this type of brachytherapy afterloading system and can easily be performed by mail to any institution in the European area and elsewhere. Such an external audit can be an efficient QC method complementary to internal quality control as it can reveal some errors which are not observable by other means.  相似文献   
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