Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. @*Materials and Methods@#Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. @*Results@#Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). @*Conclusion@#This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Safety and effectiveness of Rixubis in patients with hemophilia B:a real-world, prospective, postmarketing surveillance study in South Korea

Background@#Rixubis (recombinant factor IX, nonacog gamma) is indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in hemophilia B patients. This real-world, postmarketing surveillance study aimed to evaluate the safety and effectiveness of Rixubis in adult and pediatric hemophilia B patients in South Korea. @*Methods@#This prospective, observational, multicenter study (clinicaltrials.gov identifier: NCT029 22231) was conducted in hemophilia B patients between April 2015 and April 2019, who were observed for up to 6 months after the initiation of Rixubis treatment. Safety was evaluated based on the number and severity of adverse events (AEs) and serious AEs (SAEs). Hemostatic effectiveness was assessed by physicians and patients by using a four-point scale and rated as excellent, good, fair, or no response based on treatment type. @*Results@#In all, 58 patients were enrolled from four centers by seven physicians during the study period. The safety and effectiveness analysis sets included 57 and 54 patients, respectively. Overall, 11 AEs were reported in eight patients (14.0%), of which three were SAEs and occurred in three patients (5.3%). All 11 AEs were reported as unexpected and mild in severity, with no anaphylactic reaction, and 10 AEs (90.9%) resolved. The majority of AEs (10) were unrelated to Rixubis. Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. @*Conclusion@#Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea.

Seroprevalence and B1 gene Phylogeny of Toxoplasma gondii of Dogs and Cats in Republic of Korea

The outbreak of human toxoplasmosis can be attributed to ingestion of food contaminated with Toxoplasma gondii. Toxoplasmosis recently increased in domestic and stray dogs and cats. It prompted studies on the zoonotic infectious diseases transmitted via these animals. Sero- and antigen prevalences of T. gondii in dogs and cats were surveyed using ELISA and PCR, and B1 gene phylogeny was analyzed in this study. Toxoplasmosis antibodies were measured on sera of 403 stray cats, 947 stray dogs, 909 domestic cats, and 2,412 domestic dogs collected at nationwide regions, Korea from 2017 to 2019. In addition, whole blood, feces, and tissue samples were also collected from stray cats (1,392), stray dogs (686), domestic cats (3,040), and domestic dogs (1,974), and T. gondii-specific B1 gene PCR was performed. Antibody prevalence of stray cats, stray dogs, domestic cats, and domestic dogs were 14.1%, 5.6%, 2.3%, and 0.04%, respectively. Antigen prevalence of these animals was 0.5%, 0.2%, 0.1%, and 0.4%, respectively. Stray cats revealed the highest infection rate of toxoplasmosis, followed by stray dogs, domestic cats, and domestic dogs. B1 gene positives were 5 of stray cats, and identified to high/moderate pathogenic Type I/III group. These findings enforce that preventive hygienic measure should be strengthened at One Health level in dogs and cats, domestic and stray, to minimize human toxoplasmosis infections.

Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma:a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study

Background@#Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. @*Methods@#We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. @*Results@#A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype.Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, highrisk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level.In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. @*Conclusion@#This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997–2016: a Nationwide Retrospective Cohort Study

Background@#Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. @*Methods@#We collected the data of a newly diagnosed pediatric HHA cohort (2007–2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997–2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. @*Results@#A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. @*Conclusion@#In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Safety and effectiveness of Rixubis in patients with hemophilia B:a real-world, prospective, postmarketing surveillance study in South Korea

Background@#Rixubis (recombinant factor IX, nonacog gamma) is indicated for the control and prevention of bleeding episodes, perioperative management, and routine prophylaxis in hemophilia B patients. This real-world, postmarketing surveillance study aimed to evaluate the safety and effectiveness of Rixubis in adult and pediatric hemophilia B patients in South Korea. @*Methods@#This prospective, observational, multicenter study (clinicaltrials.gov identifier: NCT029 22231) was conducted in hemophilia B patients between April 2015 and April 2019, who were observed for up to 6 months after the initiation of Rixubis treatment. Safety was evaluated based on the number and severity of adverse events (AEs) and serious AEs (SAEs). Hemostatic effectiveness was assessed by physicians and patients by using a four-point scale and rated as excellent, good, fair, or no response based on treatment type. @*Results@#In all, 58 patients were enrolled from four centers by seven physicians during the study period. The safety and effectiveness analysis sets included 57 and 54 patients, respectively. Overall, 11 AEs were reported in eight patients (14.0%), of which three were SAEs and occurred in three patients (5.3%). All 11 AEs were reported as unexpected and mild in severity, with no anaphylactic reaction, and 10 AEs (90.9%) resolved. The majority of AEs (10) were unrelated to Rixubis. Of the 142 hemostatic effectiveness assessments, 123 (86.6%) were reported as good or excellent. @*Conclusion@#Rixubis demonstrated an acceptable safety and effectiveness profile in the treatment of bleeding, perioperative management, and prophylaxis in hemophilia B patients in a real-world setting in South Korea.

Klebsiella pneumoniae infection secondary to bovine viral diarrhea in two prematurely born calves

Abstract: This paper describes the development of neurological signs of two prematurely born calves four days after birth. The pathological examination results indicated fibrinopurulent polyserositis, including meningoencephalitis with suppurative bronchopneumonia. Bovine viral diarrhea virus subtype 2a was detected in most of the internal organs, and the bacterial colonies cultured from the samples were identified as Klebsiella (K.) pneumoniae. Molecular analysis via multilocus sequence typing identified a different K.pneumoniae isolate in each calf-type 14 in calf A and type 65 in calf B. This is the first report identifying K.pneumoniae sequence types 14 and 65 in cattle.

A rare case of bovine tuberculosis caused by Mycobacterium bovis in a domestic rabbit

A 12-month-old domestic rabbit died suddenly without specific clinical signs. Gross examination revealed irregular yellowish hepatic nodules with pus in the submandibular muscles, lungs, uterus, and small intestines. Histopathological examination of the liver showed granulomatous inflammation with acid-fast-positive bacteria. Mycobacterium bovis SB1040 was identified by polymerase chain reaction and spoligotyping, and Pasteurella multocida was isolated from the multiple lesions. This report demonstrates the pathological features of rare bovine tuberculosis (bTB) in a domestic rabbit, the first case in the Republic of Korea. To ensure public safety, we recommend routine monitoring of rabbits to control the incidence of bTB.

Eating Out Status according to Skipping and Type of Breakfast among Male High School Students in Incheon / 대한지역사회영양학회지

Objectives@#The frequency of eating out among adolescents seems to be connected to a high rate of skipping breakfast and be interrelated to various nutritional problems. The purpose of this study was to assess the dietary habits of breakfast and eating out and investigate their relationships in male adolescents. @*Methods@#This study conducted a cross-sectional survey. Dietary habits and eating out status were surveyed among 510 male students at a high school in Incheon and compared according to their breakfast skipping and breakfast type. @*Results@#The percentages of subjects in the breakfast skipping group and breakfast group were 41.0% and 59.0%, respectively, and the breakfast group comprised a Korean meal group (74%) and a convenience meal group (26%). In the breakfast skipping group, the percentage of subjects buying and eating snacks due to hunger was 39.7%. Reasons for eating breakfast among subjects who ate breakfast were because parents prepared breakfast (41.9%) and out of habit (31.5%) in the Korean meal group, in contrast to because parents prepared breakfast (36.7%) and due to hunger (29.1%) in the convenience meal group (P < 0.001). Breakfast preparer was mother (91.4%) in the Korean meal group, in contrast to mother (67.1%) and self (20.3%) in the convenience meal group (P < 0.001). A high proportion of the breakfast group woke up at 07~07:30 or 06:30-07, whereas a high proportion of the breakfast skipping group woke up at 07~07:30 or after 07:30, showing a significant difference according to breakfast skipping (P < 0.001). A high proportion of the breakfast group spent 10,000 won (32.5%) a week eating out while a high proportion of the breakfast skipping group spent 20,000 won or more (28.2%), showing a significant difference (P < 0.01). @*Conclusions@#About 40% of male high school students skipped breakfast and consumed snacks as a solution after breakfast skipping. The students who skipped breakfast spent more money on eating out. These results show that breakfast status may be related to eating out. Therefore, practical education on food choice and meal preparation along with regular breakfast instruction is needed in male adolescents.

What Should We Consider Carefully When Performing Survival Analysis? / 임상소아혈액종양

The survival data and the survival analysis are the data and analysis methods used to study the probability of survival. The survival data consist of a period from the juncture of a start event to the juncture of the end event (occurrence event). The period is called the survival period or survival time. In this way, the method of analysing the survival time of subjects and appropriately summarizing the degree of survival is called survival analysis. To understand and analyse survival analysis methods, researchers must be aware of some concepts. Concepts to be aware of in the survival analysis include events, censored data, survival period, survival function, survival curve and so on. This review focuses on the terms and concepts used in the survival analysis. It will also cover the types of survival data that should be collected and prepared when using actual survival analysis method and how to prepare them.

A Multicenter Study on von Willebrand Disease Realities in Yeungnam Region / 임상소아혈액종양

BACKGROUND: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. However, the number of patients who register to the Korea Hemophilia Foundation (KHF) is much lower than the expected prevalence rate and only few hospitals perform tests for diagnosis autonomously. Thus, we surveyed practical realities of VWD in Yeungnam region. METHODS: Patients with VWD (N=267) who were diagnosed at eleven university hospitals from March 1995 to March 2018 were enrolled in this study. We evaluated the medical records from each hospital retrospectively. RESULTS: Two hundred and twenty-eight children and 39 adults met the diagnostic criteria for VWD. Seventy-eight (57.4%) patients had the blood type O. Fifty-eight patients were definite type 1 (21.7%), 151 were possible type 1 (56.6%), and the others were type 2. Abnormal laboratory findings were the most common factor for the diagnosis in children. VWF mutations were detected in 17 patients. Patients with a family history showed age of diagnosis of 9 y, which is higher than in those with no family history (6 yr), and also showed a higher rate of significant bleeding (32.1% vs. 14.2%). VWF:RCo and VWF:Ag tests were performed in-hospital at only 1 of 11 hospitals. Twelve of 267 patients were enrolled at the KHF (4.5%). CONCLUSION: A high rate of out-sourcing studies may result in inaccurate diagnosis. The registration rate to the KHF is still lower than the prevalence rate. A comprehensive nationwide registration system is necessary in order to identify the actual prevalence rate and promote the diagnosis of VWD in Korea.

Co-infection of Dirofilaria immitis and Japanese encephalitis virus in a spotted seal (Phoca largha) in the Republic of Korea

A 10-year-old male spotted seal presented with loss of appetite and decreased activity. Grossly, the internal organs revealed several filarial nematodes in the right ventricle of the heart and the pulmonary vessels. Histopathological examination of the brain revealed moderate nonsuppurative meningoencephalitis with glial nodules and neuronophagia. Japanese encephalitis virus (JEV) of genotype I was isolated from the brain. All nematodes were identified as Dirofilaria immitis. This is the first clinical case of co-infection with D. immitis and JEV in a seal, suggesting that the seal, may be a dead-end host, like the human and horse, for JEV.

Result Patterns and Characteristics of HBeAg and HBV DNA in Patients with Chronic Hepatitis B

BACKGROUND: Discrepancies in the results between hepatitis B e-antigen (HBeAg) and hepatitis B virus (HBV) DNA levels pose difficulties in the management of chronic hepatitis B (CHB). This study aims to better understand the different phases of CHB and to detect additional meaningful parameters for CHB patients. METHODS: We collected datasets of HBeAg and HBV DNA levels measured during 2016 and the follow-up results for CHB patients for past 3 years. We analyzed the collected data by applying the definitions of CHB clinical phase and compared the results of semi-quantitative and quantitative HBeAg assays. RESULTS: About 55% of 2,291 result pairs from CHB patients showed qualitative agreement between HBeAg and HBV DNA results. HBeAg (−) CHB was reported in 16.49%, while hepatitis B surface antigen (HBsAg) loss occurred in 0.18% among 1,146 patients annually. HBeAg reversion occurred in 2.74% of 839 patients that experienced HBeAg seroconversion. Patients with HBeAg (+) and HBV DNA (−) showed statistically significant differences in the levels and percentage abnormality of alanine aminotransferase (ALT) based on whether HBV DNA was ‘Target not detected’ or ‘Detected,

Distribution of Pathogenic Vibrio Species in the Coastal Seawater of South Korea (2017–2018)

OBJECTIVES: Pathogenic Vibrio species are widely distributed in warm estuarine and coastal environments, and can infect humans through the consumption of raw or mishandled contaminated seafood and seawater. For this reason, the distribution of these bacteria in South Korea was investigated.METHODS: Seawater samples were collected from 145 coastal area points in the aquatic environment in which Vibrio species live. Environmental data (i.e., water temperature, salinity, turbidity, and atmospheric temperature) was collected which may help predict the distribution of the species (data not shown). Seawater samples were filtered, and incubated overnight in alkaline peptone water, at 37°C. Using species-specific polymerase chain reaction methods, screening tests were performed for the hlyA, ctxA, vvhA, and tlh genes. Clones of pathogenic Vibrio species were isolated using 3 selective plating media.RESULTS: In 2017, total seawater isolation rates for Vibrio vulnificus, Vibrio cholerae (non-pathogenic, non-O1, non-O139 serogroups), and Vibrio parahaemolyticus were 15.82%, 13.18%, 65.80%, respectively. However, in 2018 isolation rates for each were 21.81%, 19.40%, and 70.05%, respectively.CONCLUSION: The isolation rates of pathogenic Vibrio species positively correlated with the temperature of seawater and atmosphere, but negatively correlated with salinity and turbidity. From 2017 to 2018, the most frequent seawater-isolated Vibrio species were V. parahaemolyticus (68.10 %), V. vulnificus (16.54%), and non-toxigenic V. cholerae (19.58%). Comprehensive monitoring, prevention, and control efforts are needed to protect the public from pathogenic Vibrio species.

Necrotizing Enteritis Caused by Pharyngostomum cordatum Infection in a Stray Cat

A stray female cat of unknown age, presenting bright red watery diarrhea, was submitted to the Animal and Plant Quarantine Agency for diagnosis. In the small intestines extracted from the necropsied cat, numerous white oval-shaped organisms were firmly embedded in the mucosa and there was thickening of intestinal wall. Histopathological analysis revealed severe necrotizing enteritis, together with atrophied intestinal villi, exfoliated enterocytes, and parasitic worms. Recovered worms were identified as Pharyngostomum cordatum by morphological observation and genetic analysis. Although P. cordatum is known to occur widely in Korea, this is the first clinical description of an infection by P. cordatum causing severe feline enteritis.

Safety and Efficacy of B-domain Deleted Third Generation Recombinant Factor VIII (GreenGene F™) in Korean Patients with Hemophilia A: Data from a Post-marketing Surveillance Study

BACKGROUND: New B-domain deleted third generation recombinant factor VIII (FVIII; GreenGene F™, beroctocog alfa) was launched in 2010. We determined safety and efficacy of GreenGene F™ during routine clinical practice in patients with hemophilia A over a period of 12 months. METHODS: From July 2010 to July 2014, a total of 136 hemophilia A patients were enrolled in a post-marketing surveillance (PMS) study. Among them, 134 patients were assessed for drug safety and 114 patients were analyzed for drug efficacy. Patients with differing hemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. RESULTS: Among 134 patients evaluated, 85 (63.4%) had severe hemophilia. Ninety-two received a total of 1,266,077 units for prophylaxis, and 42 received 516,491 units for bleeding episodes. Three patients developed inhibitors. In 112 previously treated patients, one patient (0.9%) developed inhibitor after intensive FVIII treatment for surgery. Among 22 previously untreated patients, inhibitors were observed in 2 infants (9.1%). Overall, there were a total of 47 adverse events (other than inhibitors) of all types in 30 patients (22.4%), 11 in 10 patients (7.5%) of which were considered showing serious adverse events (SAEs); most of which were hemorrhages at different sites. None of the SAEs were judged as product related. An excellent/good efficacy rate of 91.3% for hemostasis and 89.4% for hemorrhage prevention was recorded. CONCLUSION: The results of this PMS study support the use of GreenGene F™ as safe and efficacious in hemorrhage prevention and treatment of hemophilia A. These results are consistent with the findings from previously published GreenGene F™ studies.

Sudden death caused by trichlorfon poisoning in Korean native cattle / 대한수의학회지

Two 12-month-old cattle with anthelmintics containing trichlorfon the day before death presented to the Animal and Plant Quarantine Agency for diagnosis. In necropsy, they revealed enlargement of the spleens, redness of mucosa and serosa in stomachs and intestines, and friable kidneys. Histopathologically, hemorrhages in the spleens, omasums, abomasums, and intestines as well as renal tubular necrosis were observed. Trichlorfon was detected at above the lethal dose in the ruminal contents. Based on these findings, we diagnosed this case as death caused by trichlorfon poisoning.

Ectopic migration of Dirofilaria immitis in a Eurasian otter (Lutra lutra) in Korea / 대한수의학회지

An 8-year-old female Eurasian otter (Lutra lutra) reared in a wetland center, died 2 h after sudden onset of astasia and dyspnea despite medical treatment. Gross examination of internal organs revealed 10 adult filarioid nematodes in the right ventricle of the heart and three between the left and right cerebral hemispheres. All nematodes were identified as Dirofilaria immitis by direct microscopy and polymerase chain reaction assay. Histopathological observation revealed multifocal hemorrhage in the cerebral subarachnoid space and focal necrosis with hemorrhagein the cerebellar parenchyma. Although rare, veterinarians should consider cerebral dirofilariasis as a differential diagnosis in unexplained neurological cases.

Meningoencephalitis and pneumonia caused by Pasteurella multocida in rabbits / 대한수의학회지

Eight rabbits exhibited head tilt and subsequently died. At necropsy, three rabbits had crusty deposits in ears and four had reddish lungs. The main histopathological features were severe diffuse suppurative meningoencephalitis (75.0% of rabbits), fibrinopurulent pneumonia (37.5%), and otitis externa (37.5%). Pasteurella multocida (P. multocida) was isolated from brains, ears, and lungs. The capsular serogroups of the isolates were untypable. Based on histopathological features and bacterial analysis results, the rabbits were diagnosed as P. multocida infection. P. multocida infections might result in considerable economic loss in commercial rabbit production facilities in Korea.

Survey and Solutions for the Current Status of Quality Control in Small Hospital Laboratories

BACKGROUND: To prevent medically significant errors, hospital laboratories must perform thorough statistical quality control (QC) procedures. We surveyed the QC status of small laboratories and created new statistical QC software that they can easily use for improving QC. METHODS: A questionnaire on the status of external and internal QC was created and sent to clinics and hospitals with small-scale laboratories. We then created QC software that can be downloaded and installed for free. RESULTS: External quality assessments were performed in 32% of the clinics (22 of 66) and 52% of the hospitals (12 of 23). Seventy-three percent of all institutions (66 of 90) carried out an internal quality assessment based on their own guidelines, mostly using commercialized QC materials. However, only 52% of clinics and 23% of hospitals used their own acceptable range instead of the manufacturer's expected range. In addition, the proportion of manual QC management reached 52% in clinics and 82% in hospitals. The QC software we designed covers all the basic functions of statistical QC and aims to improve the quality of laboratories. CONCLUSIONS: We obtained basic data on the current status of external and internal QC in small-scale laboratories using this survey. Furthermore, we suggested that new QC software may actually help to improve QC of small laboratories.