New reference allelic ladders to improve allelic designation in a multiplex STR system

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples. Received: 12 August 1997 / Received in revised form: 7 November 1997     

2013年度FDA批准的创新性药物简析

美国食品药品监督管理局（FDA）于2013年度共批准27个新药,其中小分子药物25个,生物制品2个,涉及抗肿瘤、代谢和内分泌系统、抗病毒、精神神经系统、呼吸系统、伴随诊断试剂,以及医学影像产品等治疗和应用领域。与2012年批准的39个新药相比,虽然在产品数量上有所下降,但这些药物却具备广阔的商业前景。简要介绍其中的重点品种,并就新药研发的现状与趋势进行分析。     

FDA Breakthrough Therapy Designation: Evaluating the Quality of the Evidence behind the Drug Approvals

The United States Food and Drug Administration (FDA) has created approval pathways and designations to accelerate access to medications indicated for serious or life‐threatening conditions with limited treatment options. Implemented in 2012, the most recent of these is the breakthrough therapy designation (BTD). The purpose of this article was to review the evidence surrounding approval of medications with nononcology indications approved with the BTD designation from 2012 to 2016. Fifteen medications were identified for eight conditions, ranging from conditions that are relatively common, such as chronic hepatitis C infection, to those that are extremely rare, such as lysosomal acid lipase deficiency. The quality of evidence behind these approvals was highly heterogeneous. Much remains unknown about the safety and efficacy of many agents approved through the BTD. Health care professionals should be aware of these limitations to better educate patients and other providers appropriately.     

Structural variation in the alleles of a short tandem repeat system at the human alpha fibrinogen locus

This paper reports the sequences of 22 alleles identified at the HumFGA (human alpha fibrinogen) short tandem repeat locus in the British Caucasian and AfroCaribbean populations. Alleles at the lower end of the observed size range were found to increase in size by 4-bp increments with the repeat unit following the pattern TC(TCTT)_n. However, 5 alleles were identified that differed in size by 2 by from the 4 by increment as a result of the deletion of a TC dinucleotide, or the addition of a TT dinucleotide, immediately prior to the 1st repeat unit. Alleles at the upper end of the observed size range were found to have a more complex repeat unit structure and also exhibited duplication of both 5' and 3' flanking sequences. A nomenclature for the designation of HumFGA alleles is proposed on the basis of this sequence data.     

On the Other Hand

This paper presents a brief overview of the past and current state of handedness research illustrating some of the controversies. It emphasizes two aspects: the lack of agreement on the behavior that indicates to which hand-use group (left or right) an individual belongs, and the reasons for preferring one hand rather than the other for various manual activities.     

Cross-national comparative study of orphan drug policies in Saudi Arabia,the United States,and the European Union

BackgroundRare diseases are chronic, serious, and life-threatening conditions that have not received sufficient attention from drug developers due to their rarity. Policies have been implemented to encourage research and incentivize the development of orphan drugs. However, the implementation of these policies has been inconsistent worldwide.ObjectiveThe primary aim of this study was to compare orphan drug policies in the United States, Europe, and Saudi Arabia (SA) and assess their impact on the number of approved indications.MethodLists of all drugs granted orphan designations and authorized for marketing in the United States, European Union, and SA were extracted using orphan drug lists available in regulatory body databases. The availability of these drugs, regarding their approval for orphan indication and designation, was assessed and classified using Anatomical Therapeutic Chemical codes.ResultA total of 792 orphan drug designations with at least one authorized indication were identified in this study. Of these, 92% were designated by the Food and Drug Administration (FDA), and 27% were designated by the European Medicine Agency (EMA). The FDA, EMA, and Saudi Food and Drug Authority approved 753, 435, and 253 orphan drugs, respectively.ConclusionFewer orphan drug approvals were found in SA than in the United States and Europe. This highlights the need to focus on rare diseases and orphan drugs and for policies to be created in SA to attract pharmaceutical markets and fulfill unmet orphan drug approval needs.     

浅谈对药械组合产品属性界定的认识和建议

药械组合产品,是一种由药品和医疗器械组合而成的医疗产品。对这类产品的监管,首先需要确定产品的管理属性,即按药品还是按医疗器械管理。由于我国对药械组合产品的监管处于起步阶段,相关的法规尚不完善,涉及到产品属性界定的相关规定较为笼统,特别对界定属性资料没有具体明确的要求。本文在分析现有相关法规的基础上,借鉴美国FDA在组合产品管理方面的经验,结合我国药品和医疗器械监管的特点,就如何认识药械组合产品属性界定,以及明确界定属性的资料要求,提出初浅的意见和建议。     

Tetranucleotide STR system D8S1132: sequencing data and population genetic comparisons

In the present investigation of the D8S1132 locus 31 selected alleles were sequenced. In total there were 9 distinguishable alleles found to increase in size by regular 4 bp increments from 134 to 170 bp with a repeat array following the pattern (TCTA)_n TCA (TCTA)_n. One-third of the sequenced alleles exhibited an altered repeat sequence TCTG TCTA at the 3′ flanking region of the repeat array. A nomenclature for the designation of D8S1132 alleles is proposed on the basis of this sequence data and in accordance with the ISFH recommendations. The allele distribution of the D8S1132 locus has been investigated in three German populations (Halle-, Münster-, and Wiesbaden area) with frequencies ranging from 0.004 to 0.24. No deviation from Hardy-Weinberg equilibrium could be observed. The heterozygosity was 0.83 and the discrimination power 0.96 for the Halle population. Received: 20 August 1997 / Received in revised form: 17 October 1997     

Mortality association of enhanced CD44v6 expression is not mediated through occult lymphatic spread in stage II colorectal cancer

BACKGROUND AND AIMS: In the absence of other metastatic disease, the presence of lymph node metastasis remains the most important determinant of survival in colorectal cancer (CRC). Cluster designation 44 variant 6 (CD44v6) over-expression is associated with worse outcome in all stages of CRC. The CD44v6 is believed to confer metastatic potential through its facilitation of migration, extravasation and proliferation, although the specific means by which it conveys an adverse prognosis in CRC is unknown. The aim of the present study was to determine if CD44v6 over-expression in Stage II CRC subjects was associated with the presence of lymph node micrometastases. METHODS: We assessed tumour CD44v6 expression in 43 randomly sampled subjects who had resections for Stage II CRC between 1984 and 1991 by using immunohistochemistry. Micrometastases were sought in corresponding lymph node (LN) sections using keratin immunohistochemistry. RESULTS: There was a statistical trend between tumour CD44v6 over-expression and mortality (P = 0.09) and a significant relationship between LN cytokeratins and mortality (P = 0.01). There was no association between the detection of LN cytokeratins and tumour CD44v6 over-expression. CONCLUSION: We conclude that the adverse survival effect of CD44v6 over-expression is not mediated though lymphatic spread and postulate that it may therefore facilitate haematogenous metastasis.