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• A rare huge atrial septal aneurysm (ASA) was presented in a sudden infant death case. • The inferior vena cava (IVC) of the infant showed abnormal connection to the right atrium. • The abnormal connection of IVC might have affected the development of ASA. • A certain type of ASA is suggested to have pathological significance. An atrial septal aneurysm (ASA) is a rare cardiac anomaly characterized by varicose bulging of the atrial septum (oval fossa) into the left or right atrium. Pathogenesis and clinical significance of ASA are controversial. We report an autopsy case of a huge undiagnosed ASA with abnormality of the connecting site between the inferior vena cava and the right atrial ostium in a 2-month-old Japanese female who died suddenly and unexpectedly. She was born at 36 weeks 4 days (body weight 3,110 g). No abnormality was detected during pregnancy or delivery. The postnatal growth was normal with no cardiac problem detected at the 1-month checkup. The ASA bulged off in a mass to the left atrium (width, 0.8 cm; excursion ratio, 53%), reaching close to the inflow site of the right pulmonary vein, with dilation of the pulmonary vein. The connecting site between the inferior vena cava and the right atrium was atypically located 1.6 cm away from the atrioventricular groove. Although most cases of ASA in an infant resolve physiologically as the infant grows, the infant in the present case is thought to have had an exceptional pathological ASA, possibly causing supraventricular arrhythmia. The abnormality of the connecting site between the inferior vena cava and the right atrium might have affected the development and continuation of the ASA. [ABSTRACT FROM AUTHOR]

Introduction: International norms and ethical standards have suggested that compensation for research-related injury should be provided to injured research volunteers. However, statistical data of incidence of compensation claims and the rate of awarding them have been rarely reported. Method: Questionnaire surveys were sent to pharmaceutical companies and medical institutions, focusing on industry-initiated clinical trials aiming at new drug applications (NDAs) on patient volunteers in Japan. Results: With the answers from pharmaceutical companies, the incidence of compensation was 0.8%, including 0.06% of monetary compensation. Of the cases of compensation claims, 99% were awarded. In turn, with the answers from medical institutions, the incidence of compensation was 0.6%, including 0.4% of serious but not death cases, and 0.04% of death cases. Furthermore, most claims for compensation were initiated by medical institutions, rather than by the patients. On the other hand, with the answers from clinical trial volunteers, 3% of respondents received compensations. These compensated cases were 25% of the injuries which cannot be ruled out from the scope of compensation. Conclusion: Our study results demonstrated that Japanese pharmaceutical companies have provided a high rate of compensation for clinical trial-related injuries despite the possibility of overestimation. In the era of global clinical development, our study indicates the importance of further surveys to find each country's compensation policy by determining how it is being implemented based on a survey of the actual status of compensation coming from statistical data. [ABSTRACT FROM AUTHOR]

This paper presents a field measurement of a simple antenna system mounted on a vehicle by utilizing a geostationary test satellite called Engineering Test Satellite VIII (ETS-VIII). Our developed antenna system is compact, lightweight, and promising for low-cost production. The antenna system is constructed by a 16-cm patch array antenna, which has simple satellite tracking that is controlled by a control unit as the vehicle's bearing is updated from a navigation system in real time. A Global Positioning System (GPS) module is utilized for the navigation system to provide accurate information of the vehicle's position and bearing during traveling. A control unit is provided as antenna-beam control and measured-data acquisition. We thoroughly examine the developed system in field measurements under open field areas and blockage areas in order to evaluate the propagation characteristics caused by utility poles, pedestrian overpasses, and vegetation-covered roads. In this measurement, the received signal power and the average bit error rate (BER) are simultaneously retrieved. Steadily received levels and average BER are satisfactorily attained during satellite tracking in open field areas. Moreover, the fade characteristics and average BER performance are also investigated during signal blockage. The results show that different environments give different degrees of attenuation, which affects the BER performance in terms of fade depth. Ultimately, our proposed antenna system can contribute to the design of future cost-effective mobile satellite communications. [ABSTRACT FROM PUBLISHER]

Kampo medicines are the main traditional herbal medicines in Japan and are classified as pharmaceuticals. They are based on ancient Chinese medicine and have evolved to the Japanese original style over a long period of time. Ethical Kampo formulations are prescribed in general practice by physician under the National Health Insurance reimbursement system. Over-the-counter (OTC) Kampo formulations can be purchased and used for self-medication in primary health care settings. Kampo medicines have a substantial role in the Japanese healthcare system. In the early 1970s, “The Internal Assignments on the Review for Approval of OTC Kampo Products”, known as “210 OTC Kampo Formulae”, was published by the Ministry of Health and Welfare (currently the Ministry of Health, Labour and Welfare). In 2008, “210 OTC Kampo Formulae” was revised and presented as “The Approval Standards for OTC Kampo Products” and now 294 Kampo formulae are listed in the standards. These products have had wide spread usage in Japan. Crude drugs and Kampo extracts have been listed in The Japanese Pharmacopoeia. Both The Approval Standards and The Quality Standards play a key role in regulation of Kampo products. “Application Guideline for Western Traditional Herbal Medicines as OTC Drugs” was published in 2007. Other ethnopharmaceuticals mostly from Europe could be approved as OTC drugs in Japan. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioma (EH) is a benign vascular lesion. It is generally found in the dermis, subcutis, and rarely in visceral organs. We identified incidental EHs of the right coronary artery and right ventricle during an autopsy of Japanese female whose cause of death was liver cirrhosis. The tumor of the coronary artery originated from the tunica media of the artery and proliferated into the intima and out of the vascular wall. It resulted in marked luminal narrowing of approximately 50%–75% stenosis. However, no evidence of myocardial ischemia was found. Cardiac EH is rare and this is the first report of EH arising in the coronary artery, to our knowledge. [ABSTRACT FROM AUTHOR]

• Autopsy findings of post COVID-19 vaccine death were investigated. • Causal relationships between cause of death and vaccine were also investigated. • Many cases showed no definite causal relationship between vaccination and death. • There were a few cases showing possible adverse events, such as myocarditis. • Performing autopsy is necessary for detecting vaccine related death. COVID-19 vaccines have been used across Japan since 17 February 2021, and as of 17 April 2022, 1690 deaths potentially caused by vaccine-related adverse effects have been reported to the Ministry of Health, Labour and Welfare. However, the causal relationship between vaccination and death could not be fully evaluated because of a lack of sufficient information. Autopsy cases in which deaths occurred within seven days after COVID-19 vaccination in Tokyo Metropolis and were handled by medical examiners were selected (n = 54). Age, sex, vaccine-related information, cause of death, and possible causal relationship between vaccination and death were examined. The mean age of the deceased individuals was 68.1 years, and the study sample consisted of 34 males (63.9%) and 20 females (37.0%). Thirty-seven and six individuals received Comirnaty and Spikevax, respectively (68.5% and 11.1% respectively). The manner of death included natural (n = 43), non-natural (n = 8), and undetermined (n = 3). The most frequent cause of death was ischemic heart disease (n = 16). Regarding causal relationships, 46 cases (85.2%) did not show a causal relationship to vaccination, except for myocarditis (n = 3), thrombosis-related death (n = 4), and others (n = 1). Although many cases of deaths after COVID-19 vaccination in this study showed no definite causal relationship between the vaccination and deaths, some cases showed possible adverse events such as myocarditis. Autopsies are essential for detecting vaccine-related deaths, and the Japanese death investigation system needs to be reinforced from this viewpoint. [ABSTRACT FROM AUTHOR]

Abstract: Oral bisphosphonates (BPs) represent the first line of prevention and treatment for osteoporosis. However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs. Although absolute risk is suggested to be low, information to date on the relative risk or attributable risk has in fact been limited. Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs. Using an electronic medical records retrieval system and manual confirmation of OMJ, we conducted a retrospective cohort study of patients taking medications for osteoporosis at Kyoto University Hospital between November 2000 and October 2010. To evaluate relative risks of oral BPs for OMJ, logistic regression analysis was performed and odds ratios (ORs) and 95% confidence interval (CIs) were estimated. In addition, sensitivity analyses were performed according to hierarchical diagnosis. A total of 4129 patients (59.6%) were prescribed BPs while 2794 (40.3%) received other osteoporosis drugs. Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25–0.66 to 0.69–1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0–0.17 to 0.022–0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38–0.39 to 0.80–0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9–12.9) to 6.0 (1.3–26.1) for confirmed cases only. In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind. [Copyright &y& Elsevier]

Abstract: Allele frequencies and haplotypes for 16 Y-chromosome STR loci, DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, Y GATA H4, and DYS385a/b, were determined in 161 unrelated Japanese males using AmpFlSTR® Yfiler™ PCR Amplification Kit. This population was demonstrated 153 haploytpes, of which 146 were unique, six were found in two individuals, and one was found in three individuals. The haplotypes diversity calculated from the 16 Y-STR loci was 0.9994 and the discrimination capacity was 0.9503. [Copyright &y& Elsevier]

Fifteen short tandem repeat (STR) loci D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA were analyzed in 164 unrelated Japanese using the PowerPlex® 16 System kit. The genotype frequency distribution of each locus did not deviate from the Hardy–Weinberg equilibrium. Penta E was the best STR for forensic purpose. The combined power of discrimination (PD) was 0.999999999999999978. [Copyright &y& Elsevier]

Background: The Precision ID Ancestry Panel with 165 SNP markers was unable to differentiate between mainland Japanese and Okinawa Japanese or to distinguish either of them from other East Asian populations., Aim: An Okinawa panel was developed with the aim of further separating Okinawa Japanese individuals from mainland Japanese and other Asian groups. Seventy-five SNPs were selected using the most informative markers from the literature. Further, 22 SNPs were selected to separate Okinawa Japanese at minimum SNPs., Subjects and Methods: Samples were collected from 48 unrelated individuals from mainland Japan and 46 unrelated residents of the Okinawa prefecture. Data were evaluated by STRUCTURE, principal component, and GenoGeographer analyses., Results: The 22 SNP set had similar levels of differentiation in STRUCTURE and PCA analyses as the 75 SNP set. GenoGeographer analysis showed that, out of the 46 Okinawa Japanese individuals, the 75 SNP and 22 SNP sets correctly assigned the Okinawan population as the most likely population of origin for 32 and 31 individuals, respectively., Conclusion: Neither SNP set could completely differentiate between Okinawa Japanese and other Asian groups, however, these sets should be useful for crime investigation, when the sample, cost and time are limited.

In this study, we propose a stutter ratio for a minus two base pair stutter (-2bpSR) model of the D1S1656 locus in capillary electrophoresis (CE)-based short tandem repeat (STR) typing. DNA from a total of 108 Japanese individuals was analyzed via massively parallel sequencing to investigate the length of the longest uninterrupted stretch of two base repeat motif (2bpLUS value) within repetitive structures involving the flanking region. Additionally, -2bpSR data was collected using the GlobalFiler Kit on a 3500xL Genetic Analyzer. As a result of sequencing analysis, all alleles were classified into two types by their 2bpLUS values. The -2bpSR differed significantly between the types. Then, we modeled the -2bpSR with a mixture log-normal distribution using the classification of alleles based on the 2bpLUS values. Furthermore, probabilities of the sequence type within each repeat number in the mixture log-normal distribution model were estimated using logistic regression for each of the five major detected populations. This study is expected to enable interpretation of STR typing while considering minus two base pair stutter at the D1S1656 locus., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A total of 344 unrelated Japanese adults were genotyped to determine allele frequencies and evaluate forensic parameters for 10 autosomal supplementary non-CODIS loci and 2 autosomal CODIS loci using an Investigator® HDplex Kit for complex relationship testing.

We typed 165 AIMs in 49 mainland Japanese and 47 Okinawa Japanese using the Precision ID Ancestry Panel (Thermo Fisher Scientific). None of the 165 SNPs showed significant deviation from Hardy-Weinberg equilibrium in the mainland Japanese. One SNP (rs3943253) showed significant deviation from Hardy-Weinberg equilibrium in Okinawa Japanese. Fisher's exact tests showed that the genotype frequencies of 14 loci were significantly different (p<0.05) between the two populations before correction for multiple testing. After Bonferroni correction, only rs671 remained statistically significant (p<0.0003). This SNP is located in the ALDH2 gene. The mutant A allele is associated with increased side effects after alcohol intake. The frequency of the GG genotype (wild type) was higher in the Okinawa Japanese (78.7%) than in mainland Japanese (34.7%; Bonferroni corrected P<0.001). For 31 (63.3%) of the mainland Japanese and 42 (89.4%) of Okinawa Japanese, the highest population likelihood was obtained with the Japanese reference population. However, only in a few individuals, the likelihoods were significantly different from those calculated using reference data from neighboring populations. The likelihoods for mainland Japanese and Okinawa Japanese were not significantly different from each other for any of the investigated individuals. STRUCTURE and PCA analyses showed that mainland Japanese, Okinawa Japanese, and East Asians could not be differentiated with the Precision ID Ancestry Panel., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Phenomena known as null alleles and peak imbalance can occur because of mutations in the primer binding sites used for DNA typing. In these cases, an accurate statistical evaluation of DNA typing is difficult. The estimated likelihood ratio is incorrectly calculated because of the null allele and allele dropout caused by mutation-induced peak imbalance. Although a number of studies have attempted to uncover examples of these phenomena, few reports are available on the human identification kit manufactured by Qiagen. In this study, 196 Japanese individuals who were heterozygous at D2S1360 were genotyped using an Investigator HDplex Kit with optimal amounts of DNA. A peak imbalance was frequently observed at the D2S1360 locus. We performed a sequencing analysis of the area surrounding the D2S1360 repeat motif to identify the cause for peak imbalance. A point mutation (G>A transition) 136 nucleotides upstream from the D2S1360 repeat motif was discovered in a number of samples. The allele frequency of the mutation was 0.0566 in the Japanese population. Therefore, human identification or kinship testing using the Investigator HDplex Kit requires caution because of the higher frequency of single nucleotide polymorphisms at the primer binding site of D2S1360 locus in the Japanese population.

Objective: This study aims to demonstrate the protective effect on mortality among participants of a health education program, Brain-Oriented Obesity Control System (BOOCS)., Methods: A quasi-experimentally designed, 15-year (1993 to 2007) follow-up study was conducted with a total of 13,835 male and 7791 female Japanese workers. They were divided into three groups: participants in the program (1565 males and 742 females), nonparticipant comparative obese controls (1230 males and 605 females), and nonparticipant reference subjects (11,012 males and 6426 females). Hazard ratios were calculated with survival curves drawn to evaluate the mortality effects by the program participation., Results: The male participants showed significantly lower mortality risk for all causes of death at hazard ratio = 0.54 (95% confidence interval: 0.31 to 0.94) with significantly different survival curves (P = 0.014 by log-rank test) than obese controls., Conclusions: The results support a protective effect on mortality by participating in BOOCS program.

This paper presents calculated specific absorption rate (SAR) dosimetry in 4 and 8 week Japanese pregnant-woman models exposed to plane waves over the frequency range of 10 MHz-1.5 GHz. Two types of 2 mm spatial-resolution pregnant-woman models comprised a woman model, which is similar to the average-sized Japanese adult female in height and weight, with a cubic (4 week) embryo or spheroidal (8 week) one. The averaged SAR in the embryos exposed to vertically and horizontally polarized plane waves at four kinds of propagation directions are calculated from 10 MHz to 1.5 GHz. The results indicate that the maximum average SAR in the embryos exposed to plane waves is lower than 0.08 W kg(-1) when the incident power density is at the reference level of ICNIRP guideline for general public environment.

Since the diversification of the electromagnetic (EM) environment is spreading, it is essential to estimate the EM energy absorption rate [specific absorption rate (SAR)] of a pregnant woman's body and her fetus under various exposure situations. For example, if pregnant women work in jobs where they might wear business portable radios around their abdomens, they should also be concerned about this issue, because the fetuses are in their abdomens. In this paper, in order to evaluate the SAR in the pregnant woman and her fetus when wearing the wireless radio terminal on her abdomen, the SAR distribution in the fetus is calculated using the numerical model of the pregnant woman by exposed to near-field of a normal mode helical antenna (NHA) with a metallic case at 150 MHz. In addition, the SAR in the fetus will be evaluated under two fetal positions. It was found that the fetal SARs are greatly affected by the distance and penetration path from the antenna to the fetal surface. In addition, the fetal SARs are lower than the RF safety guidelines for occupational exposure.

We studied eight X-STRs (DXS7132, DXS7423, DXS8378, DXS10074, DXS10101, DXS10134, DXS10135, HPRTB) polymorphism in 494 unrelated Japanese individuals (313 males, 181 females) using Mentype Argus X-8 PCR Amplification Kit. PD of the eight X-STRs ranged from 0.558 (male) to 0.987 (female). Allele frequencies, number of alleles, and PIC were 0.001-0.587, 6-20, and 0.470-0.913, respectively.

To describe qualitatively recent changes in the Japanese clinical trial environments, we compared the results of the Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (FY1997 to FY1999) with those from April 2002 to March 2003 (FY2002). In addition, the audit results were compared between the United States and Japan. The audit findings in the former period were based on the official audits by the Organization for Pharmaceutical Safety and Research (OPSR) that covered 331 hospitals and 775 trials. The audits by the OPSR in the latter period targeted 136 hospitals and 226 trials. The total number of deficiencies detected in the Good Clinical Practice audits in the former 3-year period (FY1997 to FY1999) was 1529, and the number in the single year (FY2002) was 1627. The total number of deficiencies detected and reported was about 3-fold on an annual basis between the periods. By category of deficiencies, there were 2 remarkable changes in the OPSR's audit findings between FY1997-FY1999 and FY2002. One was an increase in the proportion of protocol deviations from 14.7% (225/1529) in FY1997-FY1999 to 48.2% (785/1627) in FY2002, and the other was a decrease in the proportion of case report form-related deficiencies from 43.6% (666/1529) to 16.0% (260/1627). The high prevalence of protocol nonadherence and the relatively few findings of informed consent errors were important characteristics of Japanese trials inferred from the audit result reported by the OPSR in FY2002. In the United States, relatively high proportions of protocol nonadherence and informed consent errors were observed in the audit finding reported in 1997. Although the audit results for clinical trials between the United States and Japan are not strictly comparable, our results suggest that protocol deviations are a compelling issue for quality improvement in the conduct of clinical trials for the 2 regions.

Background: Although overall Japanese approval times declined after the establishment of a new review agency, they still vary significantly from one new drug application (NDA) to another. The causes of these variations have not been investigated quantitatively., Objective: To investigate associations between the approval times and properties of the NDAs such as the results and quality of clinical trials and to examine the Japanese NDA review system., Methods: For the NDAs approved between 1996 and 2003, the characteristics of NDAs including application and approval dates, review status, applicant characteristics, and clinical results were obtained from a survey and other public sources. Regulatory characteristics at different times including the number of NDAs in backlog were also estimated from several sources., Results: Approval times varied significantly across therapeutic categories, review teams, and before and after the new review agency. Use of consultation services and prior number of NDA submissions were negatively associated with the length of approval times. Merger and acquisition experience of the applicants, the amount of clinical data, and the number of NDAs in backlog in the review teams were associated with longer approval times. The way of efficacy establishment was not associated with the length of approval times, but safety profiles of products were associated with the time. Use of foreign clinical data was generally not associated with the length of approval times., Conclusions: Several characteristics of applicants, burdens on the reviewers, clinical data package, and regulatory mandates such as predefined time-line goals were associated with the outcome of the review process in Japan.

The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan.

Objective: This study evaluated the utilisation of human pharmacology studies with biomarkers for either efficacy or safety estimation conducted for new drug applications (NDAs) submitted to the Japanese regulatory authority, the Ministry of Health, Labour and Welfare (MHLW)., Methods: A total of 50 new chemical entities (NCEs) posted on the Websites, which were approved from June 2000 to November 2001, were evaluated by investigating their approval information. The utilisation of human pharmacology studies with biomarkers was evaluated by focusing on the classification referred to biomarkers for either efficacy or safety estimation and timing of studies., Results: The human pharmacology studies with biomarkers for either efficacy or safety estimation were conducted in 20 compounds classified by utilising measures of either efficacy (17 compounds) or safety (seven compounds). In 4 of 17 NCEs, some of the biomarkers in human pharmacology studies were similar to the clinical endpoints for efficacy assessment in therapeutic exploratory and/or therapeutic confirmatory studies. For safety assessment in therapeutic exploratory and/or therapeutic confirmatory studies, clinical endpoints rather than biomarkers in human pharmacology studies were used in all seven NCEs. The timing of each type of clinical study could only be obtained for 15 NCEs. Of these 15 NCEs, human pharmacology studies with biomarkers for either efficacy or safety estimation were conducted on six compounds. There were only two compounds for which human pharmacology studies with biomarkers for efficacy estimation were conducted before pivotal studies such as a therapeutic exploratory study or a bridging study., Conclusion: Our survey suggests that with Japanese NDAs, human pharmacology studies with biomarkers for either efficacy or safety estimation do not play a key role in accelerating drug development and maximising the knowledge gained from confirmatory trials. The relationship between a biomarker and a clinical endpoint should be investigated appropriately for accelerating drug development. We think that the utilisation of human pharmacology studies with biomarkers for either efficacy or safety estimation in the regulatory review process for NDAs should be encouraged with the advancements of drug evaluation research using an appropriate biomarker based on clinical pharmacology.

Background: Japanese clinical trials have some unique characteristics in both design and conduct. We have studied recent changes in quality in Japanese clinical trials., Objective: To describe quantitatively recent drastic changes in Japanese clinical trial environments by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year [FY] 1997-1999) with those from April 2000 to March 2001 (FY2000)., Methods: The numbers and proportions of various types of deficiencies described in GCP audit reports were compared between the 2 periods. The audit findings in the former period were based on official audits that covered 331 hospitals and 775 trials. The audits in the latter period targeted 123 hospitals and 279 trials. In both periods, inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR)., Results: The total number of deficiencies detected in GCP audits in the former 3-year period (FY1997-1999) was 1529; the number in the next single year (FY2000) was 1151. The total number of deficiencies detected and reported was more than double on an annual basis between the periods. By category of deficiencies, the proportion of protocol deviations increased from 14.7% (n = 225) to 41.4% (n = 477), while the proportion of errors in Case Report Forms decreased from 43.6% (n = 666) to 34.1% (n = 392)., Conclusions: This study shows that the protocol deviations increased in FY2000. The increase in deficiencies may be associated with the regulatory change of applicable standards, increasing attention of the OPSR to such deficiencies, difficulties in improving investigators' behaviors during a short period of time, and insufficient numbers of support staff including clinical research coordinators in research institutions.

Nine short tandem repeat (STR) loci, D3S1358, D5S818, vWA, TH01, D13S317, TPOX, FGA, D7S820 and CSF1PO, were investigated in semen stains of various ages using the AmpFLSTR Profiler Kit. The nine STR loci were typed from semen stains stored for up to 25 years with the application of 1-10 ng DNA. This system provides a useful tool in medicolegal individualization of aged semen stains. During this investigation we found a new variant allele 18.1 at the vWA locus.