Implementer-initiated adaptation of evidence-based interventions: kids remember the blue wig.

Adaptation of evidence-based interventions by implementers is widespread. Although frequently viewed as departures from fidelity, adaptations may be positive in impact and consistent with fidelity. Research typically catalogs adaptations but rarely includes the implementers' perspectives on adaptation. We report data on individuals implementing an evidence-based teen dating violence prevention curriculum. Key informant interviews (n = 20) and an online focus group (n = 10) addressed reasons for adaptations, adaptation processes and kinds of adaptations. All implementers described making adaptations, which they considered necessary to achieving intended outcomes. Adaptations were tailored to needs of individual students or learning opportunities presented by current events, fine-tuned over repeated applications and shared with colleagues. Adaptations modified both content and delivery and included both planned and in-the-moment changes. Implementers made adaptations to increase student engagement, and to fit students' learning needs, learning style, social maturity and culture. Student engagement served as an indicator that adaptation might be needed and provided feedback about the immediate effects of the adaptation. These findings underscore the value of fidelity assessments that measure participant response, intervention-specific guidance to implementers and evaluation of the impact of adaptations on participant response and intervention outcomes.

Structural studies on some tamoxifen derivatives.

The crystal structures of four derivatives of the antiestrogenic drug tamoxifen are described. These are of 2-hydroxy-, 3-hydroxy-, and 2-methyl-4-hydroxytamoxifen and of 1-(4-methoxyphenyl)-2-phenyl-1-[(tetrahydropyran-2-yloxy)phenyl]-1 -butanol, the synthetic precursor to 2-hydroxytamoxifen. All compounds have trans stereochemistry about the ethylene double bond, as in tamoxifen itself. The orientations of the hydroxy substituents have been found to differ by 180 degrees, depending on the nature of the compound. Empirical energy calculations have been used to show that the barrier to free rotation for the hydroxy-substituted phenyl rings is too high for interconversion to take place. These orientational differences are, it is suggested, related to the marked differences in estrogen receptor binding ability.

New HLA DNA polymorphisms associated with rheumatoid arthritis.

Studies of restriction enzyme fragment length polymorphisms (RFLP) have further clarified two DNA polymorphisms detected in DR4 positive individuals with a DQ beta probe. These patterns have been designated DQ beta omega, characterized in the Dw4 homozygous typing cell (HTC) BM14 and DQ beta phi, characterized in the Dw4 HTC MCF, and so do not correspond with different Dw types. These patterns clearly segregate in families with HLA haplotypes. We suggest that omega and phi may be polymorphisms of the DX beta gene. The previously reported DX alpha polymorphisms U and L were found with all DR types and in association with DQ beta omega (U) and DQ beta phi(L). In addition DQ beta phi was found to be strongly associated with TA10 positively (a subdivision of DQw3) although this association was not absolute. Associations between RFLP and other HLA Class II and I antigens seen in DR4 patients and DR4 controls suggest the existence of at least two preferential allelic associations (PAA), one containing omega/U and the other phi/L. PAA1: DX alpha U-DQ beta omega-TA10 negative-DQw3-Dw4-DR4----Bw62-Bw6-Cw3-A2 PAA2: DX alpha L-DQ beta phi-TA10 positive-DQw3-Dw4-DR4----B44-Bw4-Cw3-A2 The frequency of the omega pattern was higher, although not significantly in the RA patients compared with controls. However, a significantly higher frequency of omega was found in RA patients with extra-articular manifestations (EA) compared (a) with controls (p less than 0.04) and (h) with those patients without EA (p less than 0.05). In addition the frequency of phi was significantly higher in RA patients with nodules and/or erosions (N/ER) compared with patients without these features (p less than 0.008). When cumulative scores were assigned to patients after assessing the number of components fulfilled for each PAA, PAA1 appeared to be pronounced in patients with EA and PAA2 in patients with N/ER. The frequency of a previously reported DQ beta T6 band found with the enzyme Taq 1 and DQ-beta probe was found at a higher frequency in RA patients compared with controls. In addition a significantly higher frequency of this band was found in female RA patients compared to males.

Association of DR4 related RFLP bands and RA in Greeks.

Using the Taq1 restriction enzyme and DR beta, DQ alpha probes, the DNAs of Greek RA patients and controls were characterised for RFLP's associated with DR4. Three DR beta bands, 14.8kb, 6.1kb and 5.4kb were observed at significantly higher frequency in the patients compared with controls. By using a DQ alpha probe, the 2.6kb band (associated with DR1, DRw10, DRBR and DRw14 (Dw9)) was at a significantly raised frequency in the patients. The DQ alpha 5.3kb band associated with DR4, DR7 and DR9 was also raised in the RA patients although this increase did not reach statistical significance. In view of the previously documented lack of association between DR4 (and other DR antigens) and RA in Greeks, the results suggest that some degree of HLA class II association exists with RA in this population at the DNA level which may not be overtly reflected serologically.

The antitumor complex ethylenediamine platinum (II) malonate: x-ray structure analysis, and studies of its stability in solution.

The anti-tumour compound ethylenediamine platinum (II) malonate has been examined by x-ray crystallography. The molecular structure has a square-planar arrangement around the platinum atom, with the malonate group in a boat conformation and cis to the ethylenediamine group. Solution studies have shown that the malonate ion may be readily displaced from the complex, especially by chloride ion, and at low pH. The implications of this finding for in vivo drug administration are discussed.

X-ray crystallographic analysis of (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene: molecular structure of a 'syn' diol epoxide.

X-ray crystallographic analysis has been used to define the molecular structure of the cis (syn) diol epoxide, (+/-)-7 beta,8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. The two hydroxyl groups are oriented equatorially to the tetrahydrobenzene ring, contrary to predictions and there is no intramolecular hydrogen bonding in the structure.

HLA antigen and haplotype frequencies in Greeks.

A random panel of 189 healthy Greek subjects was HLA typed for A, B and DR antigens. The alleles of these loci were found to be in Hardy-Weinberg equilibrium. Compared with other European Caucasoid populations, the frequencies of A9, B5, B18, B35, DR2 and DR5 were raised and that of B8 lowered. Significant linkage disequilibrium was found between a number of A/B, B/DR and A/DR antigen combinations. Some of the antigen associations usually seen in Caucasoid populations were also present in this sample (A1-B8-DR3, B14-DR1, B15-DR4) although others were missing (A3-B7-DR2, B35-DR1, B44-DR4). In addition, some antigen combinations have not been previously described. The most frequent two locus haplotypes in the Greek population are B8-DR3 and B18-DR5.

HLA-DR4 associated Dw types in rheumatoid arthritis.

Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p less than 0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p less than 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p less than 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data. Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3. BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2 = 2.1 p = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

New HLA DNA polymorphisms associated with autoimmune diseases.

Certain class II determinants of the human histocompatibility locus antigens (HLA) have been implicated in the aetiology of several autoimmune diseases, including rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus (IDDM). HLA-Dw4 was the first HLA determinant found to be significantly increased in RA patients compared with controls, while Dw4 and Dw3 were found to be significantly increased in IDDM patients. When the HLA-DR system was defined, RA patients were found to have an increased frequency of DR4 and IDDM patients an increased incidence of both DR4 and DR3 compared with controls. As the HLA-Dw specificities are narrower than the serologically defined DR specificities, it was of specific interest to the present study that Dw4, Dw10, Dw13, Dw14, Dw15 and DKT2 are included in DR4. We describe here new restriction fragment length polymorphisms (RFLPs) and, together with the newly described serologically defined DQ specificity TA10, test their prevalence and associations in controls and diseased patients. We find that the newly characterized DNA bands are present at a much higher frequency in RA and IDDM patients than in controls. These findings may lead to a greater understanding of the pathogenesis of such diseases.

Distribution of HLA-DQA1, -DQB1 and DRB1 alleles in black IDDM patients and controls from Zimbabwe.

We have used the XI Histocompatibility Workshop sequence-specific oligonucleotide probes to determine the DRB1, DQA1 and DQB1 genotypes by dot-blot hybridization of polymerase chain reaction (pcr)-amplified material from a homogenous black population in Zimbabwe. The DR4 subtype DRB1*0405, the DR3 subtype DRB1*0301, DQB1*0201 and DQB1*0302 and DQA1*0301 and DQA1*0501 were significantly increased in the IDDM group compared to the controls, whereas DRB1*11, DQB1*0602 and DQA1*0102 were significantly decreased. Taken together, the data show that susceptibility and resistance to IDDM are associated both with particular haplotypes and DQA1-DQB1 heterodimers without one or other being overriding.

HLA-D region heterogeneity in a Nigerian population.

HLA class II antigens were studied in a panel of 130 Nigerians. Complex patterns of associations were seen between HLA-Dw, -DR and -DQ specificities, differing widely from those reported for other populations. A number of Dw types were associated with the same DR antigen: Dw'1N' and Dw'BERN' with DR1, Dw2 and Dw'2N' with DR2, Dw5 and Dw'5N' (Dw5 + Dw'F5') with DRw11. It was also observed that a Dw type associated with more than one DR antigen: HLA-Dw3 was assigned to individuals who were DR3 negative and similarly Dw10, Dw13 and Dw14 to individuals negative for DR4. HLA-DRw8 and Dw8 were completely dissociated in Nigerians, and Dw8 did not show a preferential DR association. These results demonstrate that DR and DQ identity between HTC stimulator and responder cell is not necessarily a prerequisite for Dw to be assigned. Preliminary studies show that subtypes of HLA-Dw1 and Dw8 detected by HTC typing correlate with restriction fragment length polymorphisms (RFLPs) detected with a combination of Bgl II enzyme and DRA/DRB cDNA probes. HLA-DP antigen frequencies differed between Nigerians and British Caucasoids. The most common DP antigen in Nigerians was DPw1, compared with DPw4 in Caucasoids. HLA-DPw6 appeared to be absent or rare in both Nigerians and British Caucasoids. Only five out of 68 Nigerians tested were assigned two DP specificities. The association between HLA-DR3 and DPw1 reported in Caucasoid panels was absent in Nigerians.

HLA-DP polymorphism in Sudanese controls and patients with insulin-dependent diabetes mellitus.

Human leukocyte antigen (HLA) genes are candidates for susceptibility to insulin-dependent diabetes mellitus (IDDM). The association of IDDM with particular DR and DQ alleles has been reported in all populations studied, but its association with HLA-DP alleles has been controversial. To address this question we analyzed 19 DPB1 and 2 DPA1 alleles and their associations in well-characterized Sudanese (an admixture of Arab and Black) IDDM patients (n = 71) and ethnically matched controls (n = 86) using polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) typing. There were no significant differences between the patient and control groups in the DPB1 frequencies. DPB1*0201, *0401 and DPA1*01 were the most frequent alleles in both IDDM patients and control subjects. Significant positive and negative associations between DPB1 and DPA1 alleles were detected in both groups. A novel DPB1 allele included in DPB1*1701 was identified.

Synthesis and biophysical studies of short oligodeoxynucleotides with novel modifications: a possible approach to the problem of mixed base oligodeoxynucleotide synthesis.

The syntheses of 1,2-dideoxy-D-ribofuranose and 1,2-dideoxy-1-phenyl-beta-D-ribofuranose are described. Oligodeoxynucleotides containing these analogues have been synthesised and hybridized to their complementary strands. Hypochromicity studies have shown that these duplices are less stable than either the totally complementary duplex or those containing A.C and G.T mismatches.

Heterogeneity of HLA-DR4 in Greeks including a unique DR4-DQw2 association.

It has been shown that Greek RA patients do not show an increased frequency of HLA-DR4 compared with Greek controls. As only the Dw4 and Dw14 subtypes of DR4 are implicated in RA, we have characterised DR4-positive Greek RA patients and controls using serology, MLC typing and RFLP analysis to see whether the distribution of DR4 subtypes or other HLA antigens associated with DR4 could account for these findings. In the 10 patients and 12 controls studied, Dw10 was common, being present in almost half the controls. Dw4 was not detected in the controls, but was present in three of the RA patients, indicating that there may be some relationship between Dw4 and RA in this population; Dw13 and Dw14 were also found, Dw15 was not detected. Eight of the subjects did not type as any of the HLA-D antigens mentioned. Three controls had unusual DR4-DQ associations, two having DR4-DQw2 and one possessing DR4-DQw4. Analysis of the TaqI DRB RFLP of the subjects showed that one control did not have the 6.1 kb band characteristic of DR4s. All these results indicate that DR4 is a heterogeneous antigen in this population and that several as yet undescribed variants of DR4 may be present.

Sequence-specific oligonucleotide typing in Shona patients with rheumatoid arthritis and healthy controls from Zimbabwe.

Seventy-two patients with rheumatoid arthritis (RA) and 82 controls have been typed with the XI Histocompatibility Workshop DRB1 and DQB1 sequence-specific oligonucleotide probes. The increase of DRB1*04 corresponds to an increase of the serologically defined DR4, previously found in a small group of Zimbabwean RA patients and we now show that this increase is due to the subtype DRB1*0405 in association with DQB1*0302. In addition there is a clearcut increase of DRB1*1001 equivalent to the serologically defined DR10. There was no increase amongst RA patients of DRB1*0102 which was the predominant DR1 sub-type amongst controls. In the course of our investigation, we observed a DRB1*04 variant which corresponds to DRB1*0412, newly defined in the XIth Histocompatibility Workshop.