To relate genetic variation in Graves' disease (GD) susceptibility to polymorphism at MHC loci, clinical and family studies were undertaken in eastern Hungary. Among 1980 relatives of 534 index patients, 2.9% of siblings, 2.7% of offspring, and 3.0% of parents had GD. HLA haplotype combinations in affected sibling pairs were determined in the present data and combined with data in the literature (12 sibling pairs from Farid 1981, 12 from Chan et al. 1980, and 15 from Sasazuki et al. 1983); 43, 23, and 1 affected sibling pairs shared, respectively, 2, 1, and 0 HLA haplotypes. This distribution is inconsistent with simple dominant inheritance, but is consistent with simple recessive inheritance of HLA-related susceptibility over a range of gene frequencies (0.2-0.4). A frequency of 0.3 gives the best fit and is consistent with penetrance of 7.1% for the recessive susceptibility genotype; the data, however, can accommodate penetrance values up to 16%. The distribution of HLA haplotypes in 33 families related disease susceptibility more strongly to DR than to other loci. The distribution of HLA-B8 genotypes in 256 patients was in close agreement with Hardy-Weinberg equilibrium proportions, also favoring recessive inheritance of MHC-related susceptibility. The probability that an individual will be affected with GD can be predicted, based on sex, HLA genotype, and family history. For example, 14.9% of DR3-positive women with an affected first degree relative are likely to be affected. These predictions can be tested as family data accumulate.

The dynamic optimality conjecture is perhaps the most fundamental open question about binary search trees (BST). It postulates the existence of an asymptotically optimal online BST, i.e. one that is constant factor competitive with any BST on any input access sequence. The two main candidates for dynamic optimality in the literature are splay trees [Sleator and Tarjan, 1985], and Greedy [Lucas, 1988;Munro, 2000;Demaine et al. 2009]. Despite BSTs being among the simplest data structures in computer science, and despite extensive effort over the past three decades, the conjecture remains elusive. Dynamic optimality is trivial for almost all sequences: the optimum access cost of most length-n sequences is Θ(n log n), achievable by any balanced BST. Thus, the obvious missing step towards the conjecture is an understanding of the "easy" access sequences, and indeed the most fruitful research direction so far has been the study of specific sequences, whose "easiness" is captured by a parameter of interest. For instance, splay provably achieves the bound of O(nd) when d roughly measures the distances between consecutive accesses (dynamic finger), the average entropy (static optimality), or the delays between multiple accesses of an element (working set). The difficulty of proving dynamic optimality is witnessed by other highly restricted special cases that remain unresolved; one prominent example is the traversal conjecture [Sleator and Tarjan, 1985], which states that preorder sequences (whose optimum is linear) are linear-time accessed by splay trees; no online BST is known to satisfy this conjecture.In this paper, we prove two different relaxations of the traversal conjecture for Greedy: (i) Greedy is almost linear for preorder traversal, (ii) if a linear-time preprocessing 1 is allowed, Greedy is in fact linear. These statements are corollaries of our more general results that express the complexity of access sequences in terms of a pattern avoidance parameter k. Pattern avoidance is a well-established concept in combinatorics, and the classes of input sequences thus defined are rich, e.g. the k = 3 case includes preorder sequences. For any sequence X with parameter k, our most general result shows that Greedy achieves the cost n2 α(n) O(k) where α is the inverse Ackermann function. Furthermore, a broad subclass of parameter-k sequences has a natural combinatorial interpretation as k-decomposable sequences. For this class of inputs, we obtain an n2 O(k 2 ) bound for Greedy when preprocessing is allowed. For k = 3, these results imply (i) and (ii). To our knowledge, these are the first upper bounds for Greedy that are not known to hold for any other online BST. To obtain these results we identify an input-revealing property of Greedy. Informally, this means that the execution log partially reveals the structure of the access sequence. This property facilitates the use of rich technical tools from forbidden submatrix theory.Further studying the intrinsic complexity of k-decomposable sequences, we make several observ...

We investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves' disease, 62 with ophthalmopathy and 55 without. With Graves' disease per se, there is a closer association with HLA-DR3 than with B8. The opposite was true for Graves' patients with ophthalmopathy (odds ratio for ophthalmopathy associated with B8 was 12.4 and with DR3 was 7.7, both with P less than 0.0005). HLA-DR7 interacts with B8 in modifying the risk for eye disease; using the phenotype B8- DR7- as reference, the odds ratios were 16.7 for B8+ DR7+, 8.7 for B8+ DR7- and 0.26 for B8- DR7+. Thus, DR7 enhanced the risk for ophthalmopathy in the presence of B8+ but had a protective influence in its absence. Although Gm showed no association with eye disease, it modified the risk for ophthalmopathy associated with HLA-B8; the odds ratios were 20.9 for B8+ Gmfb homozygozity (fb+), 15.3 for B8+ fb- and 1.7 for B8- fb+ (B8- fb- = 1.00). We conclude that the genetic factors contributing to Graves' ophthalmopathy are different from those related to liability for Graves' hyperthyroidism.

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Fifty-two patients with thyroid epithelial cell cancer were studied for evidence of association with human leukocyte antigens (HLA). Twenty-eight patients (53.8%) and 19.4% of 160 controls were HLA-DRI-positive, conferring a relative risk of 4.85 (x2 = 21.3, P < 0.0001). HLA-DRl was increased in all histologic types of thyroid cancer. Interestingly 10 of 12 patients with metastatic disease were DR1-positive compared to 18 of 41 patients without metastases (relative risk = 6.1, xz = 4.7, P < 0.05). This study suggests that major histocompatibility complex-linked gene@) determine susceptibility to and the biologic behavior of thyroid cancer. Cancer 58:52-54, 1986. ECENT EVIDENCE suggests that the course of epithelial

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